PARADIGM pathway analysis of mRNASeq expression and copy number data - Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Aurora B signaling	172
Aurora C signaling	122
Endothelins	118
Signaling events regulated by Ret tyrosine kinase	109
Angiopoietin receptor Tie2-mediated signaling	105
p75(NTR)-mediated signaling	98
PDGFR-alpha signaling pathway	87
FOXM1 transcription factor network	87
HIF-1-alpha transcription factor network	85
Integrins in angiogenesis	81

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
Aurora B signaling	0.3156	172	11556	67	-0.29	0.37	1000	-1000	-0.02	-1000
Aurora C signaling	0.2239	122	855	7	0	0.23	1000	-1000	-0.008	-1000
Endothelins	0.2165	118	11403	96	-0.4	0.16	1000	-1000	-0.028	-1000
Signaling events regulated by Ret tyrosine kinase	0.2000	109	8975	82	-0.14	0.038	1000	-1000	-0.039	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1927	105	9324	88	-0.3	0.11	1000	-1000	-0.054	-1000
p75(NTR)-mediated signaling	0.1798	98	12261	125	-0.17	0.075	1000	-1000	-0.046	-1000
PDGFR-alpha signaling pathway	0.1596	87	3867	44	-0.28	0.037	1000	-1000	-0.025	-1000
FOXM1 transcription factor network	0.1596	87	4483	51	-0.28	0.27	1000	-1000	-0.077	-1000
HIF-1-alpha transcription factor network	0.1560	85	6475	76	-0.25	0.044	1000	-1000	-0.025	-1000
Integrins in angiogenesis	0.1486	81	6854	84	-0.26	0.096	1000	-1000	-0.023	-1000
PLK1 signaling events	0.1468	80	6844	85	-0.056	0.25	1000	-1000	-0.022	-1000
Signaling events mediated by the Hedgehog family	0.1450	79	4144	52	-0.2	0.11	1000	-1000	-0.024	-1000
Reelin signaling pathway	0.1358	74	4174	56	-0.12	0.045	1000	-1000	-0.024	-1000
Cellular roles of Anthrax toxin	0.1229	67	2628	39	-0.093	0.053	1000	-1000	-0.02	-1000
S1P3 pathway	0.1174	64	2723	42	-0.39	0.031	1000	-1000	-0.021	-1000
Fc-epsilon receptor I signaling in mast cells	0.1156	63	6118	97	-0.096	0.024	1000	-1000	-0.044	-1000
Nongenotropic Androgen signaling	0.1156	63	3285	52	-0.24	0.14	1000	-1000	-0.017	-1000
Aurora A signaling	0.1083	59	3567	60	-0.14	0.22	1000	-1000	-0.014	-1000
Effects of Botulinum toxin	0.1064	58	1512	26	-0.1	0.11	1000	-1000	-0.008	-1000
Wnt signaling	0.1028	56	395	7	-0.065	0.037	1000	-1000	0	-1000
Signaling mediated by p38-alpha and p38-beta	0.0972	53	2342	44	-0.079	0.023	1000	-1000	-0.012	-1000
IGF1 pathway	0.0954	52	2979	57	-0.076	0.035	1000	-1000	-0.025	-1000
LPA4-mediated signaling events	0.0936	51	622	12	-0.11	0	1000	-1000	-0.015	-1000
TCGA08_p53	0.0936	51	357	7	-0.033	0.019	1000	-1000	-0.009	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0936	51	6180	120	-0.15	0.11	1000	-1000	-0.036	-1000
Ephrin B reverse signaling	0.0899	49	2389	48	-0.095	0.028	1000	-1000	-0.028	-1000
Glypican 1 network	0.0881	48	2322	48	-0.17	0.1	1000	-1000	-0.02	-1000
FOXA2 and FOXA3 transcription factor networks	0.0862	47	2190	46	-0.2	0.19	1000	-1000	-0.059	-1000
TCGA08_retinoblastoma	0.0844	46	369	8	-0.04	0.13	1000	-1000	-0.005	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0844	46	3659	78	-0.13	0.055	1000	-1000	-0.038	-1000
Noncanonical Wnt signaling pathway	0.0826	45	1171	26	-0.12	0.037	1000	-1000	-0.03	-1000
Thromboxane A2 receptor signaling	0.0826	45	4816	105	-0.14	0.048	1000	-1000	-0.028	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0771	42	1436	34	-0.017	0.029	1000	-1000	-0.026	-1000
Osteopontin-mediated events	0.0771	42	1632	38	-0.089	0.097	1000	-1000	-0.017	-1000
BMP receptor signaling	0.0752	41	3344	81	-0.23	0.043	1000	-1000	-0.023	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0752	41	2844	68	-0.15	0.074	1000	-1000	-0.062	-1000
S1P4 pathway	0.0752	41	1048	25	-0.065	0.038	1000	-1000	-0.008	-1000
Plasma membrane estrogen receptor signaling	0.0734	40	3491	86	-0.19	0.08	1000	-1000	-0.028	-1000
S1P1 pathway	0.0716	39	1423	36	-0.15	0.022	1000	-1000	-0.015	-1000
Ras signaling in the CD4+ TCR pathway	0.0716	39	669	17	-0.091	0.022	1000	-1000	-0.007	-1000
Syndecan-1-mediated signaling events	0.0697	38	1325	34	-0.05	0.16	1000	-1000	-0.018	-1000
amb2 Integrin signaling	0.0697	38	3131	82	-0.1	0.13	1000	-1000	-0.021	-1000
Ephrin A reverse signaling	0.0679	37	262	7	-0.027	0.012	1000	-1000	-0.009	-1000
EPHB forward signaling	0.0661	36	3091	85	-0.055	0.048	1000	-1000	-0.042	-1000
LPA receptor mediated events	0.0642	35	3627	102	-0.13	0.13	1000	-1000	-0.048	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0606	33	2830	85	-0.21	0.031	1000	-1000	-0.032	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0550	30	1621	54	-0.1	0.048	1000	-1000	-0.023	-1000
IL4-mediated signaling events	0.0550	30	2733	91	-0.3	0.094	1000	-1000	-0.089	-1000
Visual signal transduction: Rods	0.0550	30	1606	52	-0.057	0.11	1000	-1000	-0.017	-1000
Arf6 signaling events	0.0532	29	1849	62	-0.063	0.043	1000	-1000	-0.034	-1000
EGFR-dependent Endothelin signaling events	0.0532	29	618	21	-0.082	0.048	1000	-1000	-0.026	-1000
HIF-2-alpha transcription factor network	0.0514	28	1245	43	-0.16	0.075	1000	-1000	-0.034	-1000
FAS signaling pathway (CD95)	0.0514	28	1359	47	-0.05	0.038	1000	-1000	-0.024	-1000
S1P5 pathway	0.0495	27	470	17	-0.065	0.036	1000	-1000	-0.004	-1000
Glypican 2 network	0.0495	27	108	4	0.023	0.043	1000	-1000	0.019	-1000
Coregulation of Androgen receptor activity	0.0477	26	2040	76	-0.09	0.12	1000	-1000	-0.022	-1000
Glucocorticoid receptor regulatory network	0.0477	26	3076	114	-0.15	0.21	1000	-1000	-0.036	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0477	26	1369	52	-0.055	0.047	1000	-1000	-0.027	-1000
Calcium signaling in the CD4+ TCR pathway	0.0477	26	806	31	-0.09	0.042	1000	-1000	-0.024	-1000
Syndecan-4-mediated signaling events	0.0477	26	1767	67	-0.2	0.13	1000	-1000	-0.026	-1000
IL12-mediated signaling events	0.0459	25	2233	87	-0.3	0.061	1000	-1000	-0.054	-1000
Visual signal transduction: Cones	0.0459	25	973	38	-0.057	0.033	1000	-1000	-0.015	-1000
Syndecan-2-mediated signaling events	0.0459	25	1739	69	-0.01	0.1	1000	-1000	-0.029	-1000
Signaling events mediated by PTP1B	0.0459	25	1942	76	-0.086	0.037	1000	-1000	-0.032	-1000
Presenilin action in Notch and Wnt signaling	0.0459	25	1533	61	-0.089	0.083	1000	-1000	-0.03	-1000
TCR signaling in naïve CD8+ T cells	0.0459	25	2397	93	-0.015	0.053	1000	-1000	-0.033	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0459	25	3125	125	-0.055	0.044	1000	-1000	-0.024	-1000
TCGA08_rtk_signaling	0.0459	25	672	26	-0.096	0.032	1000	-1000	-0.006	-1000
Insulin Pathway	0.0459	25	1920	74	-0.096	0.11	1000	-1000	-0.031	-1000
Regulation of Androgen receptor activity	0.0440	24	1722	70	-0.038	0.19	1000	-1000	-0.03	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0422	23	774	33	-0.12	0.13	1000	-1000	-0.032	-1000
Canonical Wnt signaling pathway	0.0404	22	1138	51	-0.046	0.083	1000	-1000	-0.028	-1000
IL2 signaling events mediated by STAT5	0.0404	22	504	22	-0.095	0.077	1000	-1000	-0.026	-1000
BARD1 signaling events	0.0385	21	1198	57	-0.045	0.13	1000	-1000	-0.038	-1000
Hedgehog signaling events mediated by Gli proteins	0.0385	21	1384	65	-0.096	0.052	1000	-1000	-0.03	-1000
IL6-mediated signaling events	0.0385	21	1587	75	-0.088	0.089	1000	-1000	-0.032	-1000
Class I PI3K signaling events mediated by Akt	0.0367	20	1376	68	-0.082	0.21	1000	-1000	-0.016	-1000
Retinoic acid receptors-mediated signaling	0.0367	20	1176	58	-0.018	0.05	1000	-1000	-0.019	-1000
Regulation of p38-alpha and p38-beta	0.0367	20	1116	54	-0.14	0.054	1000	-1000	-0.039	-1000
BCR signaling pathway	0.0367	20	2021	99	-0.035	0.058	1000	-1000	-0.054	-1000
Regulation of nuclear SMAD2/3 signaling	0.0330	18	2470	136	-0.088	0.14	1000	-1000	-0.023	-1000
EPO signaling pathway	0.0330	18	995	55	-0.04	0.038	1000	-1000	-0.023	-1000
IFN-gamma pathway	0.0330	18	1271	68	-0.18	0.074	1000	-1000	-0.037	-1000
Nectin adhesion pathway	0.0330	18	1136	63	-0.04	0.054	1000	-1000	-0.032	-1000
Rapid glucocorticoid signaling	0.0330	18	365	20	-0.031	0.026	1000	-1000	-0.008	-1000
mTOR signaling pathway	0.0312	17	902	53	-0.029	0.025	1000	-1000	-0.022	-1000
Syndecan-3-mediated signaling events	0.0312	17	609	35	-0.06	0.095	1000	-1000	-0.014	-1000
PDGFR-beta signaling pathway	0.0312	17	1691	97	-0.021	0.05	1000	-1000	-0.034	-1000
Insulin-mediated glucose transport	0.0294	16	534	32	-0.085	0.21	1000	-1000	-0.016	-1000
IL2 signaling events mediated by PI3K	0.0294	16	935	58	-0.03	0.12	1000	-1000	-0.034	-1000
Regulation of Telomerase	0.0294	16	1680	102	-0.24	0.087	1000	-1000	-0.023	-1000
ErbB2/ErbB3 signaling events	0.0275	15	992	65	-0.076	0.048	1000	-1000	-0.041	-1000
Ceramide signaling pathway	0.0275	15	1151	76	-0.046	0.061	1000	-1000	-0.019	-1000
JNK signaling in the CD4+ TCR pathway	0.0257	14	252	17	-0.044	0.056	1000	-1000	-0.014	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0257	14	1199	83	-0.023	0.21	1000	-1000	-0.018	-1000
FoxO family signaling	0.0257	14	957	64	-0.016	0.21	1000	-1000	-0.041	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0257	14	662	45	-0.006	0.058	1000	-1000	-0.027	-1000
IL23-mediated signaling events	0.0257	14	887	60	-0.007	0.23	1000	-1000	-0.073	-1000
Signaling events mediated by PRL	0.0257	14	498	34	-0.036	0.091	1000	-1000	-0.028	-1000
Caspase cascade in apoptosis	0.0239	13	1009	74	-0.027	0.15	1000	-1000	-0.028	-1000
ErbB4 signaling events	0.0239	13	951	69	-0.05	0.054	1000	-1000	-0.022	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0239	13	365	28	-0.065	0.041	1000	-1000	-0.012	-1000
IL1-mediated signaling events	0.0239	13	862	62	-0.014	0.067	1000	-1000	-0.021	-1000
ceramide signaling pathway	0.0220	12	626	49	-0.008	0.054	1000	-1000	-0.019	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0202	11	411	37	-0.021	0.063	1000	-1000	-0.016	-1000
IL27-mediated signaling events	0.0202	11	577	51	-0.033	0.038	1000	-1000	-0.045	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0202	11	873	74	-0.05	0.077	1000	-1000	-0.042	-1000
E-cadherin signaling in keratinocytes	0.0202	11	488	43	-0.009	0.038	1000	-1000	-0.015	-1000
Signaling events mediated by HDAC Class III	0.0183	10	402	40	-0.054	0.04	1000	-1000	-0.03	-1000
E-cadherin signaling in the nascent adherens junction	0.0183	10	815	76	-0.028	0.056	1000	-1000	-0.039	-1000
Class IB PI3K non-lipid kinase events	0.0183	10	30	3	-0.022	0.022	1000	-1000	-0.018	-1000
Canonical NF-kappaB pathway	0.0165	9	388	39	-0.008	0.053	1000	-1000	-0.02	-1000
p38 MAPK signaling pathway	0.0147	8	353	44	-0.002	0.063	1000	-1000	-0.016	-1000
Signaling events mediated by HDAC Class II	0.0128	7	576	75	-0.031	0.045	1000	-1000	-0.02	-1000
Arf6 trafficking events	0.0128	7	536	71	-0.16	0.04	1000	-1000	-0.027	-1000
Class I PI3K signaling events	0.0110	6	459	73	-0.023	0.042	1000	-1000	-0.029	-1000
TRAIL signaling pathway	0.0092	5	243	48	-0.01	0.05	1000	-1000	-0.019	-1000
Signaling events mediated by HDAC Class I	0.0092	5	592	104	-0.035	0.057	1000	-1000	-0.033	-1000
Signaling mediated by p38-gamma and p38-delta	0.0092	5	79	15	-0.011	0.022	1000	-1000	-0.017	-1000
PLK2 and PLK4 events	0.0073	4	12	3	-0.011	0.025	1000	-1000	-0.014	-1000
Paxillin-dependent events mediated by a4b1	0.0073	4	177	36	-0.041	0.043	1000	-1000	-0.025	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0055	3	80	23	0.002	0.046	1000	-1000	-0.016	-1000
Arf6 downstream pathway	0.0055	3	160	43	-0.037	0.041	1000	-1000	-0.024	-1000
VEGFR1 specific signals	0.0055	3	200	56	-0.04	0.047	1000	-1000	-0.027	-1000
Arf1 pathway	0.0055	3	190	54	-0.005	0.041	1000	-1000	-0.011	-1000
a4b1 and a4b7 Integrin signaling	0.0037	2	10	5	0.022	0.034	1000	-1000	0.014	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0037	2	62	27	-0.014	0.054	1000	-1000	-0.025	-1000
Atypical NF-kappaB pathway	0.0018	1	51	31	-0.011	0.027	1000	-1000	-0.016	-1000
E-cadherin signaling events	0.0018	1	7	5	0.019	0.038	1000	-1000	0.019	-1000
Circadian rhythm pathway	0.0000	0	16	22	-0.006	0.048	1000	-1000	-0.03	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	0	0.059	1000	-1000	0	-1000
Total	NA	4219	252977	7203	-12	10	131000	-131000	-3.3	-131000

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.13	0.093	0.19	285	-0.3	6	291
STMN1	0.088	0.045	0.11	338	-10000	0	338
Aurora B/RasGAP/Survivin	0.26	0.15	0.34	408	-0.18	5	413
Chromosomal passenger complex/Cul3 protein complex	0.077	0.099	0.17	196	-0.19	18	214
BIRC5	0.23	0.11	0.29	410	-10000	0	410
DES	-0.29	0.25	-10000	0	-0.52	144	144
Aurora C/Aurora B/INCENP	0.16	0.084	0.2	365	-10000	0	365
Aurora B/TACC1	0.083	0.14	0.19	323	-0.2	83	406
Aurora B/PP2A	0.17	0.079	0.21	419	-10000	0	419
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.041	0.025	0.12	21	-10000	0	21
mitotic metaphase/anaphase transition	-0.008	0.005	-10000	0	-10000	0	0
NDC80	0.097	0.075	0.28	34	-10000	0	34
Cul3 protein complex	-0.004	0.1	-10000	0	-0.21	101	101
KIF2C	0.16	0.076	0.21	311	-10000	0	311
PEBP1	0.024	0.003	-10000	0	-10000	0	0
KIF20A	0.25	0.083	0.28	475	-10000	0	475
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.16	0.088	0.21	413	-0.23	5	418
SEPT1	0.021	0.017	-10000	0	-0.35	1	1
SMC2	0.022	0.012	0.28	1	-10000	0	1
SMC4	0.022	0.005	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.11	0.17	0.29	23	-0.42	42	65
PSMA3	0.023	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.006	0.005	-10000	0	-10000	0	0
H3F3B	0.09	0.048	0.22	16	-10000	0	16
AURKB	0.23	0.11	0.29	431	-10000	0	431
AURKC	0.024	0.02	0.28	3	-10000	0	3
CDCA8	0.18	0.13	0.29	312	-10000	0	312
cytokinesis	0.14	0.092	0.22	247	-0.3	1	248
Aurora B/Septin1	0.2	0.14	0.29	351	-0.27	7	358
AURKA	0.094	0.12	0.28	161	-10000	0	161
INCENP	0.03	0.006	-10000	0	-10000	0	0
KLHL13	-0.049	0.15	-10000	0	-0.35	104	104
BUB1	0.21	0.12	0.28	415	-10000	0	415
hSgo1/Aurora B/Survivin	0.36	0.19	0.44	449	-0.16	2	451
EVI5	0.03	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.16	0.088	0.24	196	-0.25	2	198
SGOL1	0.22	0.11	0.28	406	-10000	0	406
CENPA	0.18	0.11	0.24	375	-0.26	5	380
NCAPG	0.19	0.12	0.28	349	-10000	0	349
Aurora B/HC8 Proteasome	0.17	0.078	0.21	424	-10000	0	424
NCAPD2	0.022	0.004	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.17	0.077	0.21	427	-10000	0	427
RHOA	0.022	0.005	-10000	0	-10000	0	0
NCAPH	0.22	0.11	0.28	413	-10000	0	413
NPM1	0.087	0.12	0.24	4	-0.33	33	37
RASA1	0.019	0.036	-10000	0	-0.35	5	5
KLHL9	0.022	0.017	-10000	0	-0.35	1	1
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.17	0.077	0.21	424	-10000	0	424
PPP1CC	0.023	0.002	-10000	0	-10000	0	0
Centraspindlin	0.18	0.096	0.25	228	-0.27	2	230
RhoA/GDP	0.016	0.004	-10000	0	-10000	0	0
NSUN2	0.098	0.1	0.26	19	-0.28	27	46
MYLK	-0.079	0.16	0.22	7	-0.22	295	302
KIF23	0.041	0.054	0.29	23	-10000	0	23
VIM	0.092	0.073	0.34	18	-0.23	6	24
RACGAP1	0.031	0.017	0.3	2	-10000	0	2
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.09	0.12	0.23	1	-0.34	30	31
Chromosomal passenger complex	0.19	0.093	0.23	399	-0.28	3	402
Chromosomal passenger complex/EVI5	0.37	0.19	0.45	423	-10000	0	423
TACC1	-0.037	0.13	-10000	0	-0.35	83	83
PPP2R5D	0.023	0.004	-10000	0	-10000	0	0
CUL3	0.023	0.003	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Aurora C 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
INCENP	0.023	0.003	-10000	0	-10000	0	0
Aurora C/Aurora B/INCENP	0.15	0.083	0.19	415	-10000	0	415
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	0.012	0.039	-10000	0	-0.34	6	6
AURKB	0.23	0.11	0.28	431	-10000	0	431
AURKC	0.024	0.02	0.28	3	-10000	0	3

×

Endothelins

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
AKT1	-0.14	0.15	-10000	0	-0.3	198	198
PTK2B	0.02	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.2	0.31	-10000	0	-0.75	110	110
EDN1	-0.053	0.079	-10000	0	-0.24	41	41
EDN3	0.03	0.16	0.28	98	-0.35	55	153
EDN2	0.063	0.094	0.28	83	-10000	0	83
HRAS/GDP	-0.19	0.22	-10000	0	-0.49	146	146
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.13	0.19	-10000	0	-0.4	125	125
ADCY4	-0.14	0.16	0.3	1	-0.32	177	178
ADCY5	-0.16	0.16	0.24	2	-0.33	214	216
ADCY6	-0.13	0.15	0.3	1	-0.32	167	168
ADCY7	-0.13	0.15	0.24	2	-0.31	178	180
ADCY1	-0.14	0.16	0.24	2	-0.32	178	180
ADCY2	-0.21	0.18	-10000	0	-0.36	276	276
ADCY3	-0.13	0.15	0.3	1	-0.32	169	170
ADCY8	-0.13	0.14	-10000	0	-0.31	156	156
ADCY9	-0.15	0.17	0.3	1	-0.34	198	199
arachidonic acid secretion	-0.24	0.27	-10000	0	-0.5	226	226
ETB receptor/Endothelin-1/Gq/GTP	-0.085	0.14	-10000	0	-0.31	120	120
GNAO1	-0.065	0.16	-10000	0	-0.35	124	124
HRAS	0.021	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.12	0.14	-10000	0	-0.3	153	153
ETA receptor/Endothelin-1/Gs/GTP	-0.14	0.16	-10000	0	-0.32	187	187
mol:GTP	-0.003	0.005	-10000	0	-10000	0	0
COL3A1	-0.14	0.17	-10000	0	-0.38	139	139
EDNRB	-0.056	0.15	-10000	0	-0.35	111	111
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.16	0.19	-10000	0	-0.44	149	149
CYSLTR1	-0.14	0.16	-10000	0	-0.37	136	136
SLC9A1	-0.085	0.097	-10000	0	-0.22	134	134
mol:GDP	-0.2	0.24	-10000	0	-0.52	147	147
SLC9A3	-0.19	0.32	-10000	0	-0.7	131	131
RAF1	-0.22	0.25	-10000	0	-0.49	207	207
JUN	-0.18	0.28	-10000	0	-0.7	103	103
JAK2	-0.14	0.15	-10000	0	-0.31	192	192
mol:IP3	-0.14	0.2	-10000	0	-0.47	100	100
ETA receptor/Endothelin-1	-0.16	0.18	-10000	0	-0.35	202	202
PLCB1	0.013	0.031	-10000	0	-0.35	3	3
PLCB2	0.011	0.019	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.093	0.18	0.21	34	-0.3	187	221
FOS	-0.33	0.39	-10000	0	-0.82	195	195
Gai/GDP	-0.26	0.39	-10000	0	-0.78	182	182
CRK	0.021	0.006	-10000	0	-10000	0	0
mol:Ca ++	-0.19	0.22	-10000	0	-0.46	160	160
BCAR1	0.021	0.008	-10000	0	-10000	0	0
PRKCB1	-0.14	0.19	-10000	0	-0.46	103	103
GNAQ	0.008	0.026	-10000	0	-0.35	1	1
GNAZ	0.01	0.065	-10000	0	-0.35	17	17
GNAL	-0.031	0.13	-10000	0	-0.35	77	77
Gs family/GDP	-0.2	0.22	-10000	0	-0.47	168	168
ETA receptor/Endothelin-1/Gq/GTP	-0.14	0.19	-10000	0	-0.38	165	165
MAPK14	-0.085	0.14	0.2	2	-0.36	81	83
TRPC6	-0.21	0.34	-10000	0	-0.82	108	108
GNAI2	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.002	-10000	0	-10000	0	0
GNAI1	0.017	0.045	-10000	0	-0.35	8	8
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.086	0.15	-10000	0	-0.37	84	84
ETB receptor/Endothelin-2	-0.005	0.13	0.21	56	-0.24	107	163
ETB receptor/Endothelin-3	-0.02	0.17	0.21	87	-0.28	136	223
ETB receptor/Endothelin-1	-0.077	0.12	-10000	0	-0.28	121	121
MAPK3	-0.32	0.37	-10000	0	-0.77	199	199
MAPK1	-0.32	0.37	-10000	0	-0.77	199	199
Rac1/GDP	-0.19	0.22	-10000	0	-0.49	142	142
cAMP biosynthetic process	-0.21	0.2	0.3	4	-0.41	216	220
MAPK8	-0.22	0.35	-10000	0	-0.8	113	113
SRC	0.022	0.005	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.1	0.15	-10000	0	-0.33	124	124
p130Cas/CRK/Src/PYK2	-0.2	0.26	-10000	0	-0.58	132	132
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.19	0.22	-10000	0	-0.49	143	143
COL1A2	-0.17	0.19	-10000	0	-0.42	161	161
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.081	0.16	0.22	21	-0.3	152	173
mol:DAG	-0.14	0.2	-10000	0	-0.48	100	100
MAP2K2	-0.26	0.29	-10000	0	-0.59	209	209
MAP2K1	-0.26	0.29	-10000	0	-0.6	208	208
EDNRA	-0.15	0.18	-10000	0	-0.39	178	178
positive regulation of muscle contraction	-0.12	0.13	0.2	2	-0.3	133	135
Gq family/GDP	-0.16	0.22	-10000	0	-0.49	127	127
HRAS/GTP	-0.19	0.24	-10000	0	-0.5	146	146
PRKCH	-0.14	0.19	0.21	2	-0.47	100	102
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCA	-0.14	0.19	0.21	1	-0.48	95	96
PRKCB	-0.14	0.19	-10000	0	-0.46	108	108
PRKCE	-0.14	0.19	-10000	0	-0.46	98	98
PRKCD	-0.13	0.19	0.21	1	-0.46	100	101
PRKCG	-0.14	0.19	-10000	0	-0.46	102	102
regulation of vascular smooth muscle contraction	-0.4	0.46	-10000	0	-0.97	196	196
PRKCQ	-0.15	0.2	-10000	0	-0.45	120	120
PLA2G4A	-0.26	0.3	-10000	0	-0.56	226	226
GNA14	-0.022	0.1	-10000	0	-0.35	45	45
GNA15	0.018	0.033	0.27	7	-10000	0	7
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA11	0.007	0.052	-10000	0	-0.35	10	10
Rac1/GTP	-0.12	0.14	-10000	0	-0.3	150	150
MMP1	0.16	0.13	0.35	111	-10000	0	111

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.019	0.06	-10000	0	-0.39	9	9
Crk/p130 Cas/Paxillin	-0.12	0.13	-10000	0	-0.27	196	196
JUN	-0.086	0.12	-10000	0	-0.38	32	32
HRAS	0.022	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.062	0.14	0.23	13	-0.2	240	253
RAP1A	0.023	0.002	-10000	0	-10000	0	0
FRS2	0.023	0.003	-10000	0	-10000	0	0
RAP1A/GDP	0.017	0.001	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.061	0.14	0.23	14	-0.2	239	253
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.023	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.06	0.11	0.27	2	-0.19	231	233
RHOA	0.022	0.005	-10000	0	-10000	0	0
RAP1A/GTP	-0.057	0.12	0.43	1	-0.18	240	241
GRB7	0.038	0.074	0.32	31	-0.35	2	33
RET51/GFRalpha1/GDNF	-0.06	0.14	0.23	13	-0.2	234	247
MAPKKK cascade	-0.079	0.12	0.32	1	-0.22	213	214
BCAR1	0.021	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.077	0.13	0.27	2	-0.21	250	252
lamellipodium assembly	-0.11	0.13	-10000	0	-0.25	201	201
RET51/GFRalpha1/GDNF/SHC	-0.048	0.13	0.25	6	-0.21	192	198
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
RET9/GFRalpha1/GDNF/SHC	-0.046	0.1	0.31	1	-0.19	183	184
RET9/GFRalpha1/GDNF/Shank3	-0.062	0.11	0.27	2	-0.19	233	235
MAPK3	-0.076	0.11	0.32	12	-0.31	20	32
DOK1	0.023	0.003	-10000	0	-10000	0	0
DOK6	-0.046	0.14	-10000	0	-0.35	98	98
PXN	0.023	0.003	-10000	0	-10000	0	0
neurite development	-0.088	0.12	0.3	11	-0.26	80	91
DOK5	-0.01	0.1	0.28	1	-0.35	46	47
GFRA1	-0.14	0.19	0.28	2	-0.35	241	243
MAPK8	-0.087	0.12	0.17	1	-0.39	29	30
HRAS/GTP	-0.076	0.15	0.44	1	-0.23	227	228
tube development	-0.057	0.11	0.21	9	-0.18	228	237
MAPK1	-0.076	0.11	0.32	12	-0.31	20	32
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.076	0.1	0.15	1	-0.19	229	230
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
SRC	0.022	0.005	-10000	0	-10000	0	0
PDLIM7	0.022	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.081	0.16	0.5	1	-0.23	263	264
SHC1	0.019	0.009	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.063	0.14	0.23	11	-0.2	240	251
RET51/GFRalpha1/GDNF/Dok5	-0.075	0.15	0.25	8	-0.23	246	254
PRKCA	0	0.087	-10000	0	-0.35	31	31
HRAS/GDP	0.016	0.004	-10000	0	-10000	0	0
CREB1	-0.075	0.13	0.26	1	-0.24	183	184
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.062	0.1	0.22	1	-0.2	183	184
RET51/GFRalpha1/GDNF/Grb7	-0.054	0.14	0.25	24	-0.21	234	258
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.014	0.097	0.28	21	-0.35	27	48
DOK4	0.021	0.007	-10000	0	-10000	0	0
JNK cascade	-0.085	0.12	-10000	0	-0.37	32	32
RET9/GFRalpha1/GDNF/FRS2	-0.061	0.11	0.27	2	-0.19	233	235
SHANK3	0.021	0.007	-10000	0	-10000	0	0
RASA1	0.019	0.036	-10000	0	-0.35	5	5
NCK1	0.021	0.023	-10000	0	-0.35	2	2
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.06	0.098	0.19	2	-0.19	181	183
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.081	0.12	0.22	1	-0.21	228	229
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.083	0.13	0.22	1	-0.22	228	229
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.067	0.12	0.18	8	-0.22	187	195
PI3K	-0.14	0.19	0.3	1	-0.36	201	202
SOS1	0.023	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.053	0.11	0.26	2	-0.18	228	230
GRB10	0.022	0.017	-10000	0	-0.35	1	1
activation of MAPKK activity	-0.072	0.11	0.18	1	-0.2	147	148
RET51/GFRalpha1/GDNF/FRS2	-0.061	0.14	0.24	9	-0.2	239	248
GAB1	0.02	0.032	-10000	0	-0.35	4	4
IRS1	-0.013	0.11	-10000	0	-0.35	51	51
IRS2	-0.024	0.12	-10000	0	-0.35	66	66
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.069	0.13	0.29	1	-0.22	186	187
RET51/GFRalpha1/GDNF/PKC alpha	-0.072	0.15	0.25	8	-0.22	248	256
GRB2	0.022	0.006	-10000	0	-10000	0	0
PRKACA	0.022	0.005	-10000	0	-10000	0	0
GDNF	0.02	0.02	0.28	3	-10000	0	3
RAC1	0.022	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.077	0.15	0.23	13	-0.22	255	268
Rac1/GTP	-0.12	0.16	0.25	1	-0.29	199	200
RET9/GFRalpha1/GDNF	-0.074	0.12	0.27	2	-0.2	234	236
GFRalpha1/GDNF	-0.091	0.14	0.3	2	-0.25	234	236

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.22	0.41	0.45	2	-0.82	166	168
NCK1/PAK1/Dok-R	-0.13	0.18	-10000	0	-0.4	164	164
NCK1/Dok-R	-0.26	0.48	-10000	0	-0.95	162	162
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
mol:beta2-estradiol	0.046	0.092	0.23	109	-10000	0	109
RELA	0.022	0.004	-10000	0	-10000	0	0
SHC1	0.018	0.009	-10000	0	-10000	0	0
Rac/GDP	0.016	0.003	-10000	0	-10000	0	0
F2	0.078	0.13	0.28	144	-10000	0	144
TNIP2	0.022	0.005	-10000	0	-10000	0	0
NF kappa B/RelA	-0.23	0.46	-10000	0	-0.89	163	163
FN1	0.019	0.036	-10000	0	-0.35	5	5
PLD2	-0.28	0.49	-10000	0	-1	161	161
PTPN11	0.023	0.003	-10000	0	-10000	0	0
GRB14	0.11	0.13	0.28	190	-0.35	3	193
ELK1	-0.26	0.44	-10000	0	-0.9	163	163
GRB7	0.038	0.074	0.32	31	-0.35	2	33
PAK1	0.022	0.004	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.25	0.48	-10000	0	-0.94	162	162
CDKN1A	-0.14	0.29	0.47	1	-0.59	132	133
ITGA5	0.023	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.26	0.48	-10000	0	-0.95	163	163
CRK	0.021	0.006	-10000	0	-10000	0	0
mol:NO	-0.16	0.31	0.4	3	-0.61	166	169
PLG	-0.29	0.49	-10000	0	-1	161	161
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.22	0.38	-10000	0	-0.78	166	166
GRB2	0.022	0.006	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
ANGPT2	-0.11	0.23	-10000	0	-0.61	50	50
BMX	-0.3	0.5	-10000	0	-1	163	163
ANGPT1	-0.22	0.45	-10000	0	-1.1	109	109
tube development	-0.16	0.32	0.58	1	-0.62	162	163
ANGPT4	0.006	0.042	0.28	2	-0.35	5	7
response to hypoxia	-0.019	0.03	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.24	0.54	-10000	0	-1	162	162
alpha5/beta1 Integrin	0.033	0.007	-10000	0	-10000	0	0
FGF2	-0.17	0.18	-10000	0	-0.35	276	276
STAT5A (dimer)	-0.18	0.36	-10000	0	-0.74	136	136
mol:L-citrulline	-0.16	0.31	0.4	3	-0.61	166	169
AGTR1	-0.057	0.15	0.29	2	-0.35	113	115
MAPK14	-0.29	0.51	-10000	0	-1	166	166
Tie2/SHP2	-0.19	0.4	-10000	0	-1	98	98
TEK	-0.21	0.44	-10000	0	-1.1	96	96
RPS6KB1	-0.21	0.4	-10000	0	-0.79	165	165
Angiotensin II/AT1	-0.037	0.11	0.21	2	-0.24	113	115
Tie2/Ang1/GRB2	-0.28	0.51	-10000	0	-1	163	163
MAPK3	-0.26	0.45	-10000	0	-0.92	161	161
MAPK1	-0.26	0.45	-10000	0	-0.92	161	161
Tie2/Ang1/GRB7	-0.28	0.52	-10000	0	-1	164	164
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
MAPK8	-0.28	0.49	-10000	0	-0.99	163	163
PI3K	-0.26	0.47	-10000	0	-0.94	166	166
FES	-0.29	0.51	-10000	0	-1	166	166
Crk/Dok-R	-0.26	0.48	-10000	0	-0.95	163	163
Tie2/Ang1/ABIN2	-0.28	0.52	-10000	0	-1	164	164
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.19	0.37	0.45	2	-0.73	166	168
STAT5A	0.021	0.017	-10000	0	-0.35	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.2	0.4	0.52	2	-0.78	162	164
Tie2/Ang2	-0.23	0.43	-10000	0	-0.85	151	151
Tie2/Ang1	-0.3	0.54	-10000	0	-1.1	163	163
FOXO1	-0.19	0.38	0.46	2	-0.74	165	167
ELF1	-0.006	0.061	-10000	0	-0.13	79	79
ELF2	-0.28	0.49	-10000	0	-0.99	161	161
mol:Choline	-0.27	0.47	-10000	0	-0.95	161	161
cell migration	-0.069	0.1	-10000	0	-0.22	165	165
FYN	-0.19	0.36	0.59	1	-0.7	161	162
DOK2	0.021	0.021	0.28	3	-10000	0	3
negative regulation of cell cycle	-0.13	0.26	0.46	1	-0.53	133	134
ETS1	-0.032	0.11	-10000	0	-0.24	104	104
PXN	-0.16	0.34	0.45	4	-0.66	160	164
ITGB1	0.022	0.004	-10000	0	-10000	0	0
NOS3	-0.18	0.35	0.43	2	-0.69	166	168
RAC1	0.022	0.005	-10000	0	-10000	0	0
TNF	-0.005	0.14	0.28	56	-0.24	108	164
MAPKKK cascade	-0.27	0.47	-10000	0	-0.95	161	161
RASA1	0.019	0.036	-10000	0	-0.35	5	5
Tie2/Ang1/Shc	-0.28	0.51	-10000	0	-1	164	164
NCK1	0.021	0.023	-10000	0	-0.35	2	2
vasculogenesis	-0.14	0.28	0.4	3	-0.55	166	169
mol:Phosphatidic acid	-0.27	0.47	-10000	0	-0.95	161	161
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.16	0.31	0.4	3	-0.61	166	169
Rac1/GTP	-0.19	0.37	-10000	0	-0.73	166	166
MMP2	-0.29	0.5	-10000	0	-1	161	161

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.033	0.008	-10000	0	-10000	0	0
Necdin/E2F1	-0.076	0.15	0.21	37	-0.24	234	271
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.057	0.15	-10000	0	-0.22	222	222
NGF (dimer)/p75(NTR)/BEX1	-0.12	0.19	0.2	3	-0.29	267	270
NT-4/5 (dimer)/p75(NTR)	-0.052	0.14	0.22	19	-0.25	173	192
IKBKB	0.021	0.007	-10000	0	-10000	0	0
AKT1	-0.085	0.12	0.17	31	-0.22	197	228
IKBKG	0.023	0.004	-10000	0	-10000	0	0
BDNF	0.062	0.094	0.28	84	-10000	0	84
MGDIs/NGR/p75(NTR)/LINGO1	-0.037	0.12	0.2	6	-0.21	173	179
FURIN	0.022	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.018	0.14	0.2	70	-0.21	173	243
LINGO1	0.024	0.03	0.28	5	-0.35	1	6
Sortilin/TRAF6/NRIF	0.019	0.026	-10000	0	-10000	0	0
proBDNF (dimer)	0.062	0.093	0.28	84	-10000	0	84
NTRK1	0.019	0.044	0.28	7	-0.35	4	11
RTN4R	0.021	0.017	-10000	0	-0.35	1	1
neuron apoptosis	-0.078	0.15	-10000	0	-0.4	40	40
IRAK1	0.023	0.003	-10000	0	-10000	0	0
SHC1	-0.096	0.13	-10000	0	-0.25	191	191
ARHGDIA	0.022	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.016	0.004	-10000	0	-10000	0	0
Gamma Secretase	0.045	0.04	-10000	0	-0.18	6	6
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.11	0.18	-10000	0	-0.27	277	277
MAGEH1	-0.067	0.16	-10000	0	-0.35	129	129
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.16	0.18	-10000	0	-0.28	341	341
Mammalian IAPs/DIABLO	0.054	0.033	0.21	2	-0.19	7	9
proNGF (dimer)	-0.055	0.15	-10000	0	-0.35	113	113
MAGED1	0.021	0.023	-10000	0	-0.35	2	2
APP	0.023	0.004	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.032	0.055	0.28	23	-0.35	1	24
ZNF274	0.022	0.005	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.073	0.13	-10000	0	-0.22	217	217
NGF	-0.056	0.15	-10000	0	-0.35	113	113
cell cycle arrest	-0.079	0.11	0.24	4	-0.31	59	63
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.084	0.14	-10000	0	-0.25	204	204
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.034	0.12	0.21	17	-0.21	172	189
NCSTN	0.019	0.009	-10000	0	-10000	0	0
mol:GTP	-0.082	0.16	0.2	1	-0.25	227	228
PSENEN	0.022	0.005	-10000	0	-10000	0	0
mol:ceramide	-0.1	0.12	0.18	3	-0.23	217	220
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.072	0.12	-10000	0	-0.33	65	65
p75(NTR)/beta APP	-0.058	0.13	0.21	1	-0.24	173	174
BEX1	-0.05	0.15	0.28	2	-0.35	107	109
mol:GDP	-0.11	0.13	-10000	0	-0.25	224	224
NGF (dimer)	-0.016	0.14	0.21	42	-0.21	165	207
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.025	0.12	-10000	0	-0.19	172	172
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
RAC1/GTP	-0.066	0.13	0.18	1	-0.21	220	221
MYD88	0.022	0.004	-10000	0	-10000	0	0
CHUK	0.022	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.083	0.16	0.2	1	-0.26	227	228
RHOB	0.022	0.017	-10000	0	-0.35	1	1
RHOA	0.022	0.005	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.062	0.068	0.21	91	-10000	0	91
NT3 (dimer)	0.002	0.092	0.28	5	-0.35	32	37
TP53	-0.054	0.087	0.18	7	-10000	0	7
PRDM4	-0.1	0.12	0.18	3	-0.23	220	223
BDNF (dimer)	0.075	0.15	0.25	132	-0.19	76	208
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
SORT1	0.023	0.003	-10000	0	-10000	0	0
activation of caspase activity	-0.06	0.14	-10000	0	-0.22	222	222
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.065	0.15	-10000	0	-0.24	219	219
RHOC	0.023	0.001	-10000	0	-10000	0	0
XIAP	0.023	0.001	-10000	0	-10000	0	0
MAPK10	-0.14	0.17	0.22	4	-0.34	174	178
DIABLO	0.023	0.003	-10000	0	-10000	0	0
SMPD2	-0.1	0.12	0.18	3	-0.23	217	220
APH1B	0.018	0.039	-10000	0	-0.35	6	6
APH1A	0.019	0.009	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.079	0.16	0.2	1	-0.26	220	221
PSEN1	0.022	0.004	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.033	0.007	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.069	0.14	0.21	5	-0.26	186	191
MAPK8	-0.1	0.14	0.23	5	-0.28	155	160
MAPK9	-0.1	0.14	0.23	5	-0.28	154	159
APAF1	0.023	0.002	-10000	0	-10000	0	0
NTF3	0.002	0.092	0.28	5	-0.35	32	37
NTF4	0.032	0.055	0.28	23	-0.35	1	24
NDN	-0.15	0.18	-10000	0	-0.35	246	246
RAC1/GDP	0.016	0.003	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.056	0.14	-10000	0	-0.21	221	221
p75 CTF/Sortilin/TRAF6/NRIF	0.053	0.019	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.082	0.16	0.2	1	-0.25	227	228
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.001	0.13	-10000	0	-0.18	168	168
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.006	0.14	-10000	0	-0.19	172	172
PRKACB	0.019	0.039	-10000	0	-0.35	6	6
proBDNF (dimer)/p75 ECD	0.059	0.065	0.21	83	-10000	0	83
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.018	0.045	0.28	2	-0.35	7	9
BIRC2	0.022	0.004	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.17	0.16	-10000	0	-0.32	241	241
BAD	-0.12	0.15	0.22	4	-0.31	171	175
RIPK2	0.021	0.007	-10000	0	-10000	0	0
NGFR	-0.099	0.17	0.28	1	-0.35	174	175
CYCS	-0.094	0.11	0.2	7	-0.33	58	65
ADAM17	0.022	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.062	0.15	-10000	0	-0.23	209	209
BCL2L11	-0.12	0.15	0.23	2	-0.31	173	175
BDNF (dimer)/p75(NTR)	-0.036	0.16	0.21	70	-0.24	174	244
PI3K	-0.065	0.14	-10000	0	-0.23	215	215
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.064	0.15	-10000	0	-0.23	219	219
NDNL2	0.022	0.005	-10000	0	-10000	0	0
YWHAE	0.021	0.007	-10000	0	-10000	0	0
PRKCI	0.021	0.007	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.11	0.17	0.21	1	-0.3	224	225
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.064	0.15	-10000	0	-0.23	218	218
TRAF6	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCZ	0.022	0.02	0.28	1	-0.35	1	2
PLG	-0.006	0.11	0.28	9	-0.35	45	54
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.089	0.14	0.16	4	-0.26	208	212
SQSTM1	0.022	0.004	-10000	0	-10000	0	0
NGFRAP1	0.019	0.039	-10000	0	-0.35	6	6
CASP3	-0.12	0.15	0.22	3	-0.3	170	173
E2F1	0.071	0.1	0.28	100	-10000	0	100
CASP9	0.022	0.005	-10000	0	-10000	0	0
IKK complex	-0.057	0.14	-10000	0	-0.32	89	89
NGF (dimer)/TRKA	-0.023	0.11	0.21	5	-0.25	101	106
MMP7	0.027	0.13	0.28	62	-0.35	36	98
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.055	0.15	-10000	0	-0.22	214	214
MMP3	0.066	0.097	0.28	92	-10000	0	92
APAF-1/Caspase 9	-0.094	0.09	-10000	0	-0.29	54	54

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.094	0.16	-10000	0	-0.36	141	141
PDGF/PDGFRA/CRKL	-0.053	0.12	-10000	0	-0.25	139	139
positive regulation of JUN kinase activity	-0.002	0.088	-10000	0	-0.19	92	92
CRKL	0.022	0.005	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.056	0.12	0.19	1	-0.25	139	140
AP1	-0.28	0.36	-10000	0	-0.81	165	165
mol:IP3	-0.084	0.11	-10000	0	-0.27	129	129
PLCG1	-0.084	0.11	-10000	0	-0.27	129	129
PDGF/PDGFRA/alphaV Integrin	-0.054	0.12	-10000	0	-0.25	140	140
RAPGEF1	0.022	0.006	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.084	0.11	-10000	0	-0.27	129	129
CAV3	0.018	0.012	0.28	1	-10000	0	1
CAV1	-0.04	0.14	-10000	0	-0.35	89	89
SHC/Grb2/SOS1	-0.001	0.089	-10000	0	-0.19	92	92
PDGF/PDGFRA/Shf	-0.057	0.12	-10000	0	-0.25	143	143
FOS	-0.28	0.36	0.31	2	-0.8	164	166
JUN	-0.043	0.042	-10000	0	-0.3	7	7
oligodendrocyte development	-0.054	0.12	-10000	0	-0.25	140	140
GRB2	0.022	0.006	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
mol:DAG	-0.084	0.11	-10000	0	-0.27	129	129
PDGF/PDGFRA	-0.094	0.16	-10000	0	-0.36	141	141
actin cytoskeleton reorganization	-0.053	0.12	-10000	0	-0.25	139	139
SRF	0.005	0.02	-10000	0	-10000	0	0
SHC1	0.019	0.009	-10000	0	-10000	0	0
PI3K	-0.028	0.1	-10000	0	-0.21	114	114
PDGF/PDGFRA/Crk/C3G	-0.035	0.1	-10000	0	-0.2	139	139
JAK1	-0.077	0.1	-10000	0	-0.25	138	138
ELK1/SRF	-0.067	0.09	0.16	11	-0.22	120	131
SHB	0.022	0.004	-10000	0	-10000	0	0
SHF	0.018	0.039	-10000	0	-0.35	6	6
CSNK2A1	0.037	0.022	-10000	0	-10000	0	0
GO:0007205	-0.089	0.12	-10000	0	-0.3	130	130
SOS1	0.023	0.003	-10000	0	-10000	0	0
Ras protein signal transduction	-0.002	0.088	-10000	0	-0.19	92	92
PDGF/PDGFRA/SHB	-0.053	0.12	-10000	0	-0.25	139	139
PDGF/PDGFRA/Caveolin-1	-0.09	0.16	-10000	0	-0.31	174	174
ITGAV	0.023	0.003	-10000	0	-10000	0	0
ELK1	-0.088	0.11	0.26	1	-0.27	126	127
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
PDGF/PDGFRA/Crk	-0.053	0.12	-10000	0	-0.24	139	139
JAK-STAT cascade	-0.077	0.1	-10000	0	-0.25	138	138
cell proliferation	-0.057	0.12	-10000	0	-0.25	143	143

×

FOXM1 transcription factor network

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
NFATC3	0.2	0.4	0.79	74	-0.88	8	82
PLK1	0.18	0.18	0.48	24	-0.66	10	34
BIRC5	0.21	0.16	0.5	17	-0.92	3	20
HSPA1B	0.2	0.4	0.78	83	-0.9	8	91
MAP2K1	0.062	0.084	0.23	56	-10000	0	56
BRCA2	0.2	0.4	0.79	72	-1	8	80
FOXM1	0.22	0.45	0.88	81	-1	9	90
XRCC1	0.2	0.4	0.79	75	-0.92	7	82
FOXM1B/p19	0.001	0.34	0.72	33	-0.99	12	45
Cyclin D1/CDK4	0.2	0.37	0.71	89	-0.82	9	98
CDC2	0.21	0.42	0.82	82	-0.91	10	92
TGFA	0.19	0.37	0.7	93	-0.79	10	103
SKP2	0.21	0.4	0.79	80	-0.89	8	88
CCNE1	0.14	0.14	0.3	217	-10000	0	217
CKS1B	0.2	0.4	0.77	84	-0.86	10	94
RB1	0.16	0.25	0.51	117	-0.66	5	122
FOXM1C/SP1	0.18	0.39	0.75	69	-0.98	9	78
AURKB	0.18	0.24	0.48	18	-0.75	22	40
CENPF	0.26	0.42	0.83	107	-0.89	8	115
CDK4	0.038	0.038	0.16	2	-10000	0	2
MYC	0.14	0.35	0.7	67	-0.86	9	76
CHEK2	0.063	0.086	0.23	68	-10000	0	68
ONECUT1	0.19	0.38	0.73	87	-0.85	9	96
CDKN2A	0.059	0.14	0.24	188	-0.15	22	210
LAMA4	0.14	0.48	0.78	79	-0.94	41	120
FOXM1B/HNF6	0.19	0.4	0.76	79	-0.96	9	88
FOS	-0.023	0.61	0.79	74	-1	83	157
SP1	0.022	0.012	-10000	0	-0.15	1	1
CDC25B	0.2	0.4	0.79	77	-0.9	7	84
response to radiation	0.037	0.058	0.16	58	-10000	0	58
CENPB	0.2	0.4	0.79	78	-0.9	7	85
CENPA	0.25	0.42	0.8	105	-0.89	7	112
NEK2	0.27	0.42	0.83	110	-0.89	7	117
HIST1H2BA	0.2	0.4	0.79	74	-0.9	8	82
CCNA2	0.083	0.11	0.3	114	-10000	0	114
EP300	0.021	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.2	0.42	0.83	72	-1	9	81
CCNB2	0.25	0.41	0.8	102	-0.9	7	109
CCNB1	0.21	0.42	0.83	81	-0.92	9	90
ETV5	0.22	0.41	0.8	86	-0.93	8	94
ESR1	0.13	0.5	0.8	78	-0.98	33	111
CCND1	0.19	0.38	0.73	90	-0.83	9	99
GSK3A	0.051	0.068	0.2	32	-10000	0	32
Cyclin A-E1/CDK1-2	0.16	0.15	0.32	204	-10000	0	204
CDK2	0.029	0.026	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.051	0.076	0.19	79	-10000	0	79
FOXM1B/Cbp/p300	0.14	0.36	0.68	48	-0.92	10	58
GAS1	-0.28	0.63	0.8	71	-0.94	157	228
MMP2	0.17	0.45	0.79	75	-1.1	24	99
RB1/FOXM1C	0.18	0.37	0.7	94	-0.88	8	102
CREBBP	0.022	0.005	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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
PKM2	-0.16	0.3	0.38	8	-0.61	108	116
HDAC7	0.023	0.005	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.15	0.34	0.57	5	-0.7	96	101
SMAD4	0.023	0.005	-10000	0	-10000	0	0
ID2	-0.15	0.31	0.42	3	-0.63	100	103
AP1	-0.053	0.13	-10000	0	-0.25	162	162
ABCG2	-0.23	0.36	0.43	2	-0.64	181	183
HIF1A	-0.032	0.078	0.18	1	-0.19	22	23
TFF3	-0.12	0.36	0.44	39	-0.66	97	136
GATA2	-0.012	0.11	-10000	0	-0.35	50	50
AKT1	-0.047	0.098	-10000	0	-0.22	67	67
response to hypoxia	-0.054	0.093	0.16	2	-0.21	89	91
MCL1	-0.15	0.29	0.41	3	-0.63	93	96
NDRG1	-0.14	0.3	0.41	4	-0.62	96	100
SERPINE1	-0.15	0.31	0.42	3	-0.64	95	98
FECH	-0.15	0.31	0.42	3	-0.63	100	103
FURIN	-0.15	0.31	0.42	3	-0.63	99	102
NCOA2	0.008	0.066	-10000	0	-0.35	17	17
EP300	-0.062	0.14	0.22	2	-0.32	94	96
HMOX1	-0.15	0.31	0.45	4	-0.63	99	103
BHLHE40	-0.15	0.31	0.42	3	-0.63	98	101
BHLHE41	-0.16	0.33	0.42	3	-0.65	116	119
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.009	0.11	0.3	2	-0.28	2	4
ENG	-0.002	0.11	0.3	6	-0.26	2	8
JUN	0.018	0.043	-10000	0	-0.35	7	7
RORA	-0.16	0.32	0.42	3	-0.65	105	108
ABCB1	-0.25	0.44	-10000	0	-0.97	139	139
TFRC	-0.14	0.31	0.47	5	-0.63	94	99
CXCR4	-0.15	0.31	0.42	3	-0.63	102	105
TF	-0.15	0.32	0.45	6	-0.65	99	105
CITED2	-0.15	0.32	0.42	3	-0.64	103	106
HIF1A/ARNT	-0.14	0.39	0.66	19	-0.73	85	104
LDHA	-0.03	0.13	-10000	0	-0.62	15	15
ETS1	-0.15	0.31	0.42	3	-0.63	101	104
PGK1	-0.15	0.31	0.42	3	-0.63	101	104
NOS2	-0.15	0.32	0.42	3	-0.64	99	102
ITGB2	-0.14	0.31	0.46	5	-0.64	97	102
ALDOA	-0.15	0.31	0.42	3	-0.64	96	99
Cbp/p300/CITED2	-0.19	0.38	0.47	4	-0.75	116	120
FOS	-0.089	0.17	-10000	0	-0.35	160	160
HK2	-0.14	0.31	0.47	4	-0.64	96	100
SP1	-0.007	0.058	-10000	0	-0.13	20	20
GCK	-0.18	0.43	-10000	0	-1.2	76	76
HK1	-0.15	0.31	0.42	3	-0.63	99	102
NPM1	-0.15	0.31	0.42	3	-0.64	98	101
EGLN1	-0.15	0.3	0.42	2	-0.63	94	96
CREB1	0.026	0.003	-10000	0	-10000	0	0
PGM1	-0.15	0.31	0.42	3	-0.63	101	104
SMAD3	0.02	0.032	-10000	0	-0.35	4	4
EDN1	-0.14	0.24	-10000	0	-0.6	73	73
IGFBP1	-0.17	0.34	0.46	6	-0.67	109	115
VEGFA	-0.13	0.29	0.44	2	-0.6	97	99
HIF1A/JAB1	-0.011	0.061	-10000	0	-0.16	4	4
CP	-0.13	0.33	0.46	15	-0.64	96	111
CXCL12	-0.24	0.36	0.42	3	-0.64	180	183
COPS5	0.02	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4	0.031	0.026	-10000	0	-0.24	4	4
BNIP3	-0.15	0.31	0.42	3	-0.64	97	100
EGLN3	-0.15	0.31	0.5	2	-0.63	99	101
CA9	-0.1	0.34	0.45	43	-0.62	98	141
TERT	-0.12	0.33	0.45	30	-0.63	92	122
ENO1	-0.15	0.31	0.42	3	-0.64	96	99
PFKL	-0.15	0.31	0.42	3	-0.64	97	100
NCOA1	0.021	0.018	-10000	0	-0.35	1	1
ADM	-0.14	0.32	0.44	8	-0.63	98	106
ARNT	-0.02	0.064	-10000	0	-10000	0	0
HNF4A	0.044	0.1	0.28	73	-0.14	1	74
ADFP	-0.16	0.3	0.38	8	-0.61	108	116
SLC2A1	-0.13	0.29	0.44	3	-0.6	95	98
LEP	-0.15	0.31	0.44	4	-0.63	99	103
HIF1A/ARNT/Cbp/p300	-0.16	0.34	0.58	5	-0.7	100	105
EPO	-0.11	0.27	0.44	1	-0.75	39	40
CREBBP	-0.062	0.14	0.2	1	-0.32	94	95
HIF1A/ARNT/Cbp/p300/HDAC7	-0.15	0.34	0.57	5	-0.69	95	100
PFKFB3	-0.15	0.31	0.42	3	-0.64	96	99
NT5E	-0.17	0.34	0.42	3	-0.65	122	125

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.017	0.065	-10000	0	-0.25	31	31
alphaV beta3 Integrin	-0.12	0.15	0.2	1	-0.24	298	299
PTK2	-0.11	0.18	0.27	14	-0.38	118	132
IGF1R	0.009	0.069	-10000	0	-0.35	19	19
PI4KB	0.018	0.01	-10000	0	-10000	0	0
MFGE8	0.021	0.023	-10000	0	-0.35	2	2
SRC	0.022	0.005	-10000	0	-10000	0	0
CDKN1B	-0.12	0.19	-10000	0	-0.52	91	91
VEGFA	0.023	0.003	-10000	0	-10000	0	0
ILK	-0.1	0.17	-10000	0	-0.49	75	75
ROCK1	0.023	0.004	-10000	0	-10000	0	0
AKT1	-0.099	0.16	-10000	0	-0.46	73	73
PTK2B	-0.042	0.085	0.2	14	-0.2	89	103
alphaV/beta3 Integrin/JAM-A	-0.099	0.14	0.2	3	-0.22	276	279
CBL	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.001	0.095	0.2	3	-0.21	89	92
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.016	0.13	-10000	0	-0.24	130	130
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.048	0.11	-10000	0	-0.33	37	37
alphaV/beta3 Integrin/Syndecan-1	0.043	0.13	0.21	133	-0.2	85	218
PI4KA	0.022	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.14	0.18	-10000	0	-0.26	328	328
PI4 Kinase	0.025	0.015	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
alphaV/beta3 Integrin/Osteopontin	0.04	0.13	0.2	129	-0.2	88	217
RPS6KB1	-0.16	0.14	0.32	1	-0.36	138	139
TLN1	0.022	0.005	-10000	0	-10000	0	0
MAPK3	-0.26	0.25	-10000	0	-0.48	277	277
GPR124	-0.057	0.15	-10000	0	-0.35	112	112
MAPK1	-0.26	0.25	-10000	0	-0.48	279	279
PXN	0.023	0.003	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
alphaV/beta3 Integrin/Tumstatin	-0.012	0.12	0.2	18	-0.23	120	138
cell adhesion	-0.006	0.097	0.23	2	-0.22	85	87
ANGPTL3	0.021	0.02	0.28	3	-10000	0	3
VEGFR2 homodimer/VEGFA homodimer/Src	0.029	0.058	-10000	0	-0.21	29	29
IGF-1R heterotetramer	0.009	0.069	-10000	0	-0.35	19	19
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
TGFBR2	0.015	0.051	-10000	0	-0.35	10	10
ITGB3	-0.04	0.14	0.28	2	-0.35	90	92
IGF1	-0.046	0.14	-10000	0	-0.35	100	100
RAC1	0.022	0.005	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	-0.045	0.13	0.2	1	-0.24	161	162
apoptosis	0.023	0.003	-10000	0	-10000	0	0
CD47	0.022	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.002	0.093	0.2	1	-0.21	86	87
VCL	0.022	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.04	0.14	0.2	2	-0.25	153	155
CSF1	0.016	0.05	-10000	0	-0.35	10	10
PIK3C2A	-0.1	0.17	-10000	0	-0.49	74	74
PI4 Kinase/Pyk2	-0.096	0.13	-10000	0	-0.23	204	204
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.003	0.11	0.21	1	-0.21	101	102
FAK1/Vinculin	-0.083	0.15	0.24	13	-0.31	108	121
alphaV beta3/Integrin/ppsTEM5	-0.045	0.14	0.2	1	-0.24	161	162
RHOA	0.022	0.005	-10000	0	-10000	0	0
VTN	-0.022	0.12	0.3	3	-0.35	65	68
BCAR1	0.021	0.007	-10000	0	-10000	0	0
FGF2	-0.17	0.19	-10000	0	-0.35	276	276
F11R	-0.1	0.12	-10000	0	-0.25	219	219
alphaV/beta3 Integrin/Lactadherin	0.001	0.096	0.2	2	-0.21	88	90
alphaV/beta3 Integrin/TGFBR2	-0.001	0.1	0.2	2	-0.22	90	92
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.046	0.039	-10000	0	-0.19	10	10
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.003	0.085	0.19	2	-0.19	88	90
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.019	0.036	-10000	0	-0.35	5	5
alphaV/beta3 Integrin/Pyk2	-0.01	0.095	0.19	1	-0.2	97	98
SDC1	0.095	0.12	0.28	150	-10000	0	150
VAV3	0.026	0.085	0.24	20	-0.18	8	28
PTPN11	0.023	0.003	-10000	0	-10000	0	0
IRS1	-0.013	0.11	-10000	0	-0.35	51	51
FAK1/Paxillin	-0.084	0.15	0.26	13	-0.31	114	127
cell migration	-0.079	0.13	0.23	14	-0.29	104	118
ITGAV	0.023	0.003	-10000	0	-10000	0	0
PI3K	-0.082	0.13	-10000	0	-0.22	207	207
SPP1	0.096	0.12	0.28	153	-10000	0	153
KDR	0.001	0.088	-10000	0	-0.35	32	32
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.023	0.003	-10000	0	-10000	0	0
COL4A3	-0.001	0.12	0.28	19	-0.35	46	65
angiogenesis	-0.26	0.26	-10000	0	-0.49	272	272
Rac1/GTP	0.022	0.079	0.23	16	-10000	0	16
EDIL3	-0.048	0.14	-10000	0	-0.35	101	101
cell proliferation	-0.001	0.1	0.2	2	-0.22	90	92

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.056	0.046	0.14	15	-0.1	55	70
BUB1B	0.062	0.064	0.12	151	-0.17	14	165
PLK1	0.035	0.033	0.1	45	-0.1	7	52
PLK1S1	0.021	0.026	0.11	9	-0.18	4	13
KIF2A	0.028	0.033	0.15	12	-0.11	1	13
regulation of mitotic centrosome separation	0.035	0.033	0.1	43	-0.1	7	50
GOLGA2	0.022	0.005	-10000	0	-10000	0	0
Hec1/SPC24	0.16	0.11	0.24	318	-10000	0	318
WEE1	0.024	0.072	0.17	1	-0.29	21	22
cytokinesis	0.094	0.069	0.18	63	-0.23	8	71
PP2A-alpha B56	0.14	0.11	-10000	0	-0.54	9	9
AURKA	0.046	0.05	0.12	137	-0.2	4	141
PICH/PLK1	0.077	0.078	0.17	198	-10000	0	198
CENPE	0.033	0.035	0.15	10	-0.14	3	13
RhoA/GTP	0.016	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.029	0.033	0.15	12	-0.11	1	13
PPP2CA	0.023	0.003	-10000	0	-10000	0	0
FZR1	0.021	0.006	-10000	0	-10000	0	0
TPX2	0.089	0.047	0.12	342	-0.24	1	343
PAK1	0.021	0.004	-10000	0	-10000	0	0
SPC24	0.18	0.13	0.28	322	-10000	0	322
FBXW11	0.023	0.004	-10000	0	-10000	0	0
CLSPN	0.075	0.064	0.12	260	-0.23	8	268
GORASP1	0.022	0.004	-10000	0	-10000	0	0
metaphase	0	0.002	0.012	8	-0.011	11	19
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.016	0.016	0.051	42	-0.051	7	49
G2 phase of mitotic cell cycle	0	0.004	0.014	29	-10000	0	29
STAG2	0.023	0.001	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.005	0.087	-10000	0	-0.52	14	14
spindle elongation	0.035	0.033	0.1	43	-0.1	7	50
ODF2	0.022	0.006	-10000	0	-10000	0	0
BUB1	0.14	0.12	-10000	0	-0.58	9	9
TPT1	0.011	0.051	0.11	3	-0.19	29	32
CDC25C	0.12	0.067	0.14	327	-0.28	10	337
CDC25B	0.023	0.009	-10000	0	-10000	0	0
SGOL1	0.056	0.047	0.1	55	-0.14	15	70
RHOA	0.022	0.005	-10000	0	-10000	0	0
CCNB1/CDK1	0.055	0.064	0.19	78	-0.17	2	80
CDC14B	-0.005	0.005	-10000	0	-10000	0	0
CDC20	0.25	0.083	0.28	474	-10000	0	474
PLK1/PBIP1	0.007	0.027	0.098	33	-0.093	5	38
mitosis	-0.005	0.007	0.021	4	-0.017	109	113
FBXO5	0.022	0.03	0.13	13	-0.13	3	16
CDC2	0.002	0.003	0.009	81	-0.01	6	87
NDC80	0.042	0.071	0.29	40	-10000	0	40
metaphase plate congression	0.022	0.05	0.14	2	-0.22	18	20
ERCC6L	0.068	0.075	0.18	121	-0.17	1	122
NLP/gamma Tubulin	0.015	0.026	0.067	17	-0.091	16	33
microtubule cytoskeleton organization	0.011	0.05	0.11	3	-0.18	29	32
G2/M transition DNA damage checkpoint	-0.001	0.002	0.013	6	-10000	0	6
PPP1R12A	0.023	0.016	-10000	0	-0.35	1	1
interphase	-0.001	0.002	0.013	6	-10000	0	6
PLK1/PRC1-2	0.19	0.081	0.22	457	-0.16	1	458
GRASP65/GM130/RAB1/GTP/PLK1	0.056	0.03	-10000	0	-10000	0	0
RAB1A	0.023	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.027	0.029	0.091	48	-0.089	3	51
mitotic prometaphase	0.001	0.004	0.02	17	-10000	0	17
proteasomal ubiquitin-dependent protein catabolic process	0.051	0.069	0.18	2	-0.36	9	11
microtubule-based process	0.19	0.068	0.22	472	-0.17	1	473
Golgi organization	0.035	0.033	0.1	43	-0.1	7	50
Cohesin/SA2	0.041	0.027	0.11	9	-0.11	2	11
PPP1CB/MYPT1	0.033	0.015	-10000	0	-0.25	1	1
KIF20A	0.25	0.083	0.28	475	-10000	0	475
APC/C/CDC20	0.19	0.07	0.22	471	-0.14	2	473
PPP2R1A	0.023	0.004	-10000	0	-10000	0	0
chromosome segregation	0.007	0.026	0.097	33	-0.092	5	38
PRC1	0.034	0.053	0.28	23	-10000	0	23
ECT2	0.052	0.079	0.25	65	-10000	0	65
C13orf34	0.027	0.028	0.087	45	-0.089	4	49
NUDC	0.022	0.05	0.14	2	-0.22	18	20
regulation of attachment of spindle microtubules to kinetochore	0.061	0.063	0.12	151	-0.17	14	165
spindle assembly	0.024	0.027	0.084	32	-0.09	7	39
spindle stabilization	0.021	0.026	0.11	9	-0.18	4	13
APC/C/HCDH1	0.018	0.007	-10000	0	-10000	0	0
MKLP2/PLK1	0.19	0.068	0.22	472	-0.17	1	473
CCNB1	0.068	0.098	0.28	93	-10000	0	93
PPP1CB	0.023	0.005	-10000	0	-10000	0	0
BTRC	0.022	0.005	-10000	0	-10000	0	0
ROCK2	0.023	0.069	0.2	2	-0.31	16	18
TUBG1	0.011	0.048	0.12	1	-0.17	30	31
G2/M transition of mitotic cell cycle	0.022	0.038	0.2	5	-0.18	1	6
MLF1IP	0.003	0.027	0.11	33	-10000	0	33
INCENP	0.023	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

Figure S12. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S12. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.042	0.15	-10000	0	-0.54	31	31
IHH	-0.041	0.21	0.31	58	-0.39	123	181
SHH Np/Cholesterol/GAS1	-0.083	0.1	0.23	1	-0.19	261	262
LRPAP1	0.022	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.083	0.1	0.18	261	-0.23	1	262
SMO/beta Arrestin2	-0.038	0.16	-10000	0	-0.32	95	95
SMO	-0.056	0.15	-10000	0	-0.32	110	110
AKT1	-0.018	0.12	-10000	0	-0.48	21	21
ARRB2	0.021	0.006	-10000	0	-10000	0	0
BOC	0.011	0.065	-10000	0	-0.35	17	17
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
heart looping	-0.054	0.15	-10000	0	-0.32	110	110
STIL	-0.01	0.12	0.22	13	-0.28	28	41
DHH N/PTCH2	-0.004	0.099	-10000	0	-0.26	69	69
DHH N/PTCH1	-0.042	0.13	-10000	0	-0.24	130	130
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
DHH	-0.008	0.1	-10000	0	-0.35	44	44
PTHLH	-0.061	0.19	-10000	0	-0.59	31	31
determination of left/right symmetry	-0.054	0.15	-10000	0	-0.32	110	110
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
skeletal system development	-0.06	0.19	-10000	0	-0.59	31	31
IHH N/Hhip	-0.004	0.14	0.22	73	-0.23	122	195
DHH N/Hhip	0.016	0.091	0.21	26	-0.24	49	75
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.054	0.15	-10000	0	-0.32	110	110
pancreas development	0.032	0.068	0.28	28	-0.35	5	33
HHAT	0.017	0.033	-10000	0	-0.35	4	4
PI3K	0.027	0.029	-10000	0	-0.25	5	5
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.2	0.18	-10000	0	-0.35	321	321
somite specification	-0.054	0.15	-10000	0	-0.32	110	110
SHH Np/Cholesterol/PTCH1	-0.022	0.11	0.24	5	-0.28	30	35
SHH Np/Cholesterol/PTCH2	0.015	0.059	0.22	6	-0.2	28	34
SHH Np/Cholesterol/Megalin	0.079	0.094	0.2	173	-0.18	6	179
SHH	0.004	0.058	0.13	64	-0.25	6	70
catabolic process	-0.036	0.12	-10000	0	-0.25	128	128
SMO/Vitamin D3	-0.014	0.15	0.3	8	-0.26	104	112
SHH Np/Cholesterol/Hhip	0.03	0.059	0.21	33	-0.18	11	44
LRP2	0.11	0.12	0.28	184	-10000	0	184
receptor-mediated endocytosis	-0.008	0.14	0.23	11	-0.33	29	40
SHH Np/Cholesterol/BOC	0.017	0.054	0.22	6	-0.19	22	28
SHH Np/Cholesterol/CDO	0.006	0.069	0.22	6	-0.19	47	53
mesenchymal cell differentiation	-0.03	0.059	0.18	11	-0.2	33	44
mol:Vitamin D3	0	0.13	0.29	16	-0.29	29	45
IHH N/PTCH2	-0.021	0.15	0.2	57	-0.25	134	191
CDON	-0.014	0.11	-10000	0	-0.35	52	52
IHH N/PTCH1	-0.025	0.15	-10000	0	-0.25	128	128
Megalin/LRPAP1	0.09	0.084	0.21	177	-10000	0	177
PTCH2	0.002	0.084	-10000	0	-0.35	29	29
SHH Np/Cholesterol	0.008	0.022	-10000	0	-0.18	6	6
PTCH1	-0.037	0.13	-10000	0	-0.25	128	128
HHIP	0.032	0.068	0.28	28	-0.35	5	33

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.031	0.013	0.21	1	-10000	0	1
VLDLR	0.021	0.023	-10000	0	-0.35	2	2
CRKL	0.022	0.005	-10000	0	-10000	0	0
LRPAP1	0.022	0.004	-10000	0	-10000	0	0
FYN	0.023	0.004	-10000	0	-10000	0	0
ITGA3	0.021	0.017	-10000	0	-0.35	1	1
RELN/VLDLR/Fyn	-0.039	0.12	0.2	6	-0.21	174	180
MAPK8IP1/MKK7/MAP3K11/JNK1	0.045	0.04	-10000	0	-0.18	5	5
AKT1	-0.055	0.093	0.15	3	-0.19	168	171
MAP2K7	0.021	0.006	-10000	0	-10000	0	0
RAPGEF1	0.022	0.006	-10000	0	-10000	0	0
DAB1	0.027	0.041	0.28	13	-10000	0	13
RELN/LRP8/DAB1	-0.03	0.12	0.21	20	-0.19	180	200
LRPAP1/LRP8	0.035	0.019	0.21	5	-10000	0	5
RELN/LRP8/DAB1/Fyn	-0.02	0.12	0.21	20	-0.18	175	195
DAB1/alpha3/beta1 Integrin	-0.025	0.1	-10000	0	-0.18	159	159
long-term memory	-0.09	0.15	0.29	4	-0.22	280	284
DAB1/LIS1	-0.02	0.11	-10000	0	-0.18	170	170
DAB1/CRLK/C3G	-0.028	0.1	-10000	0	-0.18	161	161
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
DAB1/NCK2	-0.017	0.12	-10000	0	-0.18	173	173
ARHGEF2	0.018	0.01	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.12	0.18	0.28	1	-0.35	198	199
CDK5R1	0.022	0.013	0.28	1	-10000	0	1
RELN	-0.1	0.18	0.28	7	-0.35	182	189
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
RELN/LRP8/Fyn	-0.036	0.12	0.22	9	-0.21	175	184
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.092	0.15	-10000	0	-0.22	285	285
MAPK8	0.019	0.036	-10000	0	-0.35	5	5
RELN/VLDLR/DAB1	-0.033	0.11	0.2	16	-0.19	178	194
ITGB1	0.022	0.004	-10000	0	-10000	0	0
MAP1B	-0.072	0.099	0.17	11	-0.2	189	200
RELN/LRP8	-0.039	0.12	0.23	8	-0.21	179	187
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.01	0.13	0.36	6	-0.18	174	180
PI3K	0.027	0.029	-10000	0	-0.25	5	5
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.031	0.015	-10000	0	-0.25	1	1
RAP1A	-0.058	0.092	0.3	4	-0.31	1	5
PAFAH1B1	0.021	0.006	-10000	0	-10000	0	0
MAPK8IP1	0.022	0.02	0.28	1	-0.35	1	2
CRLK/C3G	0.031	0.01	-10000	0	-10000	0	0
GRIN2B	0.03	0.052	0.29	21	-10000	0	21
NCK2	0.023	0.002	-10000	0	-10000	0	0
neuron differentiation	-0.027	0.092	-10000	0	-0.31	12	12
neuron adhesion	-0.054	0.099	0.31	10	-0.3	2	12
LRP8	0.025	0.026	0.29	5	-10000	0	5
GSK3B	-0.057	0.087	0.14	2	-0.24	8	10
RELN/VLDLR/DAB1/Fyn	-0.023	0.11	0.2	16	-0.18	172	188
MAP3K11	0.022	0.004	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.053	0.1	0.16	4	-0.2	174	178
CDK5	0.022	0.005	-10000	0	-10000	0	0
MAPT	-0.003	0.08	0.66	4	-0.31	16	20
neuron migration	-0.073	0.13	0.26	11	-0.26	159	170
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.028	0.092	-10000	0	-0.31	12	12
RELN/VLDLR	-0.027	0.12	0.21	7	-0.19	176	183

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.01	0.069	-10000	0	-0.35	19	19
ANTXR2	-0.093	0.17	-10000	0	-0.35	166	166
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.017	0.024	-10000	0	-0.051	166	166
monocyte activation	-0.006	0.12	-10000	0	-0.37	43	43
MAP2K2	-0.045	0.17	-10000	0	-0.6	45	45
MAP2K1	-0.018	0.022	0.12	1	-0.077	13	14
MAP2K7	-0.017	0.022	0.12	1	-0.077	12	13
MAP2K6	-0.015	0.028	0.19	3	-0.079	11	14
CYAA	-0.062	0.085	-10000	0	-0.18	166	166
MAP2K4	-0.017	0.023	-10000	0	-0.083	15	15
IL1B	-0.017	0.045	0.17	11	-0.14	25	36
Channel	-0.042	0.11	-10000	0	-0.2	166	166
NLRP1	-0.024	0.042	-10000	0	-0.16	34	34
CALM1	0.022	0.004	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.016	0.065	-10000	0	-0.46	9	9
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.017	0.024	0.051	166	-10000	0	166
MAPK3	-0.018	0.021	-10000	0	-0.075	14	14
MAPK1	-0.018	0.021	-10000	0	-0.077	11	11
PGR	-0.062	0.081	-10000	0	-0.19	149	149
PA/Cellular Receptors	-0.047	0.12	-10000	0	-0.22	166	166
apoptosis	-0.017	0.024	-10000	0	-0.051	166	166
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.04	0.1	-10000	0	-0.19	166	166
macrophage activation	-0.018	0.026	0.13	6	-10000	0	6
TNF	0.053	0.088	0.28	66	-0.35	2	68
VCAM1	-0.006	0.12	-10000	0	-0.38	42	42
platelet activation	-0.016	0.065	-10000	0	-0.46	9	9
MAPKKK cascade	0.015	0.029	0.09	20	-0.078	10	30
IL18	-0.018	0.029	-10000	0	-0.13	16	16
negative regulation of macrophage activation	-0.017	0.024	-10000	0	-0.051	166	166
LEF	-0.017	0.024	-10000	0	-0.052	166	166
CASP1	-0.018	0.033	-10000	0	-0.11	40	40
mol:cAMP	-0.016	0.065	-10000	0	-0.46	9	9
necrosis	-0.017	0.024	-10000	0	-0.051	166	166
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.038	0.1	-10000	0	-0.18	166	166
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.071	-10000	0	-0.35	20	20
mol:S1P	-0.009	0.013	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.083	0.12	-10000	0	-0.24	164	164
GNAO1	-0.08	0.16	-10000	0	-0.36	124	124
S1P/S1P3/G12/G13	0.007	0.053	-10000	0	-0.2	16	16
AKT1	-0.065	0.17	-10000	0	-0.68	31	31
AKT3	-0.39	0.5	-10000	0	-1	204	204
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.071	-10000	0	-0.35	20	20
GNAI2	0	0.031	-10000	0	-10000	0	0
GNAI3	0.002	0.029	-10000	0	-10000	0	0
GNAI1	-0.003	0.052	-10000	0	-0.36	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	-0.011	0.071	-10000	0	-0.36	17	17
S1PR2	0.022	0.006	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.14	0.19	-10000	0	-0.33	228	228
MAPK3	-0.13	0.18	-10000	0	-0.34	188	188
MAPK1	-0.13	0.18	-10000	0	-0.34	188	188
JAK2	-0.14	0.19	-10000	0	-0.36	196	196
CXCR4	-0.14	0.18	-10000	0	-0.34	196	196
FLT1	-0.003	0.036	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
SRC	-0.13	0.18	-10000	0	-0.34	188	188
S1P/S1P3/Gi	-0.14	0.19	-10000	0	-0.33	235	235
RAC1	0.022	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.13	0.18	-10000	0	-0.33	206	206
VEGFA	-0.003	0.035	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.084	0.13	-10000	0	-0.26	151	151
VEGFR1 homodimer/VEGFA homodimer	-0.002	0.053	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.024	0.094	-10000	0	-0.26	61	61
GNAQ	0.021	0.017	-10000	0	-0.35	1	1
GNAZ	-0.009	0.068	-10000	0	-0.35	17	17
G12/G13	0.031	0.01	-10000	0	-10000	0	0
GNA14	-0.01	0.1	-10000	0	-0.35	45	45
GNA15	0.025	0.03	0.28	7	-10000	0	7
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
GNA11	0.014	0.051	-10000	0	-0.35	10	10
Rac1/GTP	-0.13	0.18	-10000	0	-0.33	202	202

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.021	0.023	-10000	0	-0.35	2	2
LAT2	-0.063	0.12	-10000	0	-0.25	121	121
AP1	-0.086	0.17	-10000	0	-0.38	81	81
mol:PIP3	-0.049	0.17	0.33	14	-0.29	117	131
IKBKB	-0.019	0.12	0.24	32	-0.22	51	83
AKT1	-0.003	0.16	0.31	71	-0.28	26	97
IKBKG	-0.029	0.11	0.26	18	-0.22	53	71
MS4A2	-0.096	0.16	-10000	0	-0.34	165	165
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
MAP3K1	-0.027	0.14	0.25	31	-0.3	43	74
mol:Ca2+	-0.034	0.14	0.22	53	-0.23	114	167
LYN	0.022	0.01	-10000	0	-10000	0	0
CBLB	-0.063	0.12	-10000	0	-0.25	124	124
SHC1	0.019	0.009	-10000	0	-10000	0	0
RasGAP/p62DOK	-0.011	0.099	-10000	0	-0.19	121	121
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.022	0.016	-10000	0	-0.35	1	1
PLD2	-0.015	0.16	0.28	92	-0.24	61	153
PTPN13	-0.078	0.16	0.32	1	-0.43	40	41
PTPN11	0.018	0.021	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.02	0.14	0.34	17	-0.27	31	48
SYK	0.024	0.014	0.28	1	-10000	0	1
GRB2	0.022	0.006	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.07	0.14	-10000	0	-0.29	122	122
LAT	-0.062	0.12	-10000	0	-0.25	119	119
PAK2	-0.03	0.15	0.25	34	-0.32	46	80
NFATC2	-0.057	0.14	-10000	0	-0.49	46	46
HRAS	-0.042	0.15	0.23	12	-0.27	115	127
GAB2	0.02	0.032	-10000	0	-0.35	4	4
PLA2G1B	-0.011	0.14	-10000	0	-0.88	13	13
Fc epsilon R1	-0.052	0.13	0.2	1	-0.23	176	177
Antigen/IgE/Fc epsilon R1	-0.044	0.12	0.19	1	-0.2	175	176
mol:GDP	-0.062	0.13	-10000	0	-0.36	44	44
JUN	0.018	0.042	-10000	0	-0.35	7	7
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
FOS	-0.089	0.17	-10000	0	-0.35	160	160
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.062	0.12	-10000	0	-0.26	127	127
CHUK	-0.029	0.12	0.31	14	-0.22	53	67
KLRG1	-0.052	0.1	0.15	1	-0.21	122	123
VAV1	-0.059	0.12	-10000	0	-0.25	113	113
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.061	0.12	-10000	0	-0.25	119	119
negative regulation of mast cell degranulation	-0.034	0.11	0.23	1	-0.29	40	41
BTK	-0.063	0.13	-10000	0	-0.37	43	43
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.067	0.13	-10000	0	-0.24	161	161
GAB2/PI3K/SHP2	-0.062	0.079	-10000	0	-0.23	62	62
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.054	0.11	-10000	0	-0.21	144	144
RAF1	-0.008	0.16	-10000	0	-0.96	13	13
Fc epsilon R1/FcgammaRIIB/SHIP	-0.031	0.12	-10000	0	-0.2	172	172
FCER1G	0.022	0.025	0.29	2	-10000	0	2
FCER1A	-0.037	0.13	-10000	0	-0.36	74	74
Antigen/IgE/Fc epsilon R1/Fyn	-0.034	0.11	0.2	1	-0.19	173	174
MAPK3	-0.011	0.14	-10000	0	-0.89	13	13
MAPK1	-0.014	0.15	-10000	0	-0.91	13	13
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
MAPK8	-0.054	0.21	-10000	0	-0.59	56	56
DUSP1	-0.062	0.16	-10000	0	-0.35	122	122
NF-kappa-B/RelA	-0.016	0.068	0.14	2	-0.14	42	44
actin cytoskeleton reorganization	-0.06	0.16	-10000	0	-0.44	30	30
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.043	0.14	-10000	0	-0.33	43	43
FER	-0.062	0.12	-10000	0	-0.25	121	121
RELA	0.022	0.004	-10000	0	-10000	0	0
ITK	-0.02	0.059	-10000	0	-0.32	14	14
SOS1	0.023	0.003	-10000	0	-10000	0	0
PLCG1	-0.051	0.15	0.26	7	-0.28	112	119
cytokine secretion	-0.019	0.042	-10000	0	-10000	0	0
SPHK1	-0.061	0.12	-10000	0	-0.25	119	119
PTK2	-0.062	0.16	-10000	0	-0.47	29	29
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.07	0.14	0.23	1	-0.29	123	124
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.05	0.17	0.32	14	-0.35	57	71
MAP2K2	-0.013	0.14	-10000	0	-0.89	13	13
MAP2K1	-0.013	0.14	-10000	0	-0.89	13	13
MAP2K7	0.021	0.006	-10000	0	-10000	0	0
KLRG1/SHP2	-0.039	0.095	0.2	3	-0.26	43	46
MAP2K4	-0.087	0.32	-10000	0	-0.91	67	67
Fc epsilon R1/FcgammaRIIB	-0.039	0.13	0.21	1	-0.21	175	176
mol:Choline	-0.015	0.16	0.28	92	-0.24	61	153
SHC/Grb2/SOS1	-0.042	0.13	-10000	0	-0.25	109	109
FYN	0.023	0.004	-10000	0	-10000	0	0
DOK1	0.023	0.003	-10000	0	-10000	0	0
PXN	-0.059	0.15	0.3	1	-0.43	30	31
HCLS1	-0.062	0.12	-10000	0	-0.25	121	121
PRKCB	-0.044	0.14	0.3	13	-0.29	59	72
FCGR2B	0.018	0.027	0.28	1	-0.35	2	3
IGHE	0	0.007	-10000	0	-10000	0	0
KLRG1/SHIP	-0.033	0.12	0.24	1	-0.29	40	41
LCP2	0.023	0.012	0.28	1	-10000	0	1
PLA2G4A	-0.069	0.12	-10000	0	-0.26	131	131
RASA1	0.019	0.036	-10000	0	-0.35	5	5
mol:Phosphatidic acid	-0.015	0.16	0.28	92	-0.24	61	153
IKK complex	-0.009	0.11	0.25	32	-0.18	33	65
WIPF1	0.021	0.023	-10000	0	-0.35	2	2

×

Nongenotropic Androgen signaling

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
PTK2	-0.006	0.002	-10000	0	-10000	0	0
GNB1/GNG2	0	0.089	-10000	0	-0.19	96	96
regulation of S phase of mitotic cell cycle	-0.014	0.072	-10000	0	-0.2	65	65
GNAO1	-0.065	0.16	-10000	0	-0.35	124	124
HRAS	0.021	0.007	-10000	0	-10000	0	0
SHBG/T-DHT	0.013	0.019	-10000	0	-0.2	4	4
PELP1	0.02	0.008	-10000	0	-10000	0	0
AKT1	-0.005	0.002	-10000	0	-10000	0	0
MAP2K1	-0.061	0.086	0.19	14	-0.26	28	42
T-DHT/AR	-0.032	0.095	-10000	0	-0.24	90	90
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.006	162	162
GNAI2	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.002	-10000	0	-10000	0	0
GNAI1	0.017	0.045	-10000	0	-0.35	8	8
mol:GDP	-0.054	0.11	-10000	0	-0.3	87	87
cell proliferation	-0.15	0.2	0.28	2	-0.41	170	172
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
FOS	-0.24	0.34	-10000	0	-0.74	166	166
mol:Ca2+	-0.02	0.029	-10000	0	-0.062	148	148
MAPK3	-0.11	0.15	0.26	3	-0.3	157	160
MAPK1	-0.083	0.14	0.2	1	-0.36	57	58
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
mol:IP3	-0.001	0.002	-10000	0	-0.004	162	162
cAMP biosynthetic process	0.005	0.025	-10000	0	-0.16	4	4
GNG2	0.017	0.049	0.28	1	-0.35	9	10
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	162	162
HRAS/GTP	-0.018	0.082	-10000	0	-0.18	77	77
actin cytoskeleton reorganization	0.027	0.023	-10000	0	-0.16	5	5
SRC	0.021	0.006	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	162	162
PI3K	0.024	0.025	-10000	0	-0.2	5	5
apoptosis	0.14	0.2	0.42	166	-0.26	1	167
T-DHT/AR/PELP1	-0.019	0.085	-10000	0	-0.21	88	88
HRAS/GDP	-0.043	0.11	-10000	0	-0.28	87	87
CREB1	-0.15	0.22	0.27	1	-0.45	166	167
RAC1-CDC42/GTP	0.034	0.026	-10000	0	-0.16	5	5
AR	-0.042	0.14	-10000	0	-0.35	90	90
GNB1	0.022	0.004	-10000	0	-10000	0	0
RAF1	-0.05	0.08	0.2	17	-0.24	26	43
RAC1-CDC42/GDP	-0.022	0.12	-10000	0	-0.28	81	81
T-DHT/AR/PELP1/Src	-0.011	0.081	-10000	0	-0.19	77	77
MAP2K2	-0.061	0.083	0.18	11	-0.27	27	38
T-DHT/AR/PELP1/Src/PI3K	-0.014	0.073	-10000	0	-0.21	65	65
GNAZ	0.01	0.065	-10000	0	-0.35	17	17
SHBG	0.019	0.033	-10000	0	-0.35	4	4
Gi family/GNB1/GNG2/GDP	-0.098	0.17	-10000	0	-0.34	141	141
mol:T-DHT	-0.001	0.001	0.002	1	-0.002	98	99
RAC1	0.022	0.005	-10000	0	-10000	0	0
GNRH1	-0.007	0.02	-10000	0	-0.24	4	4
Gi family/GTP	-0.06	0.1	-10000	0	-0.21	137	137
CDC42	0.022	0.005	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.002	0.053	0.21	1	-10000	0	1
BIRC5	0.22	0.11	0.28	410	-10000	0	410
NFKBIA	-0.006	0.055	0.21	15	-10000	0	15
CPEB1	-0.14	0.18	-10000	0	-0.35	227	227
AKT1	-0.007	0.051	0.3	4	-10000	0	4
NDEL1	0.021	0.007	-10000	0	-10000	0	0
Aurora A/BRCA1	0	0.045	-10000	0	-0.16	1	1
NDEL1/TACC3	0.037	0.091	0.22	73	-10000	0	73
GADD45A	0.023	0.002	-10000	0	-10000	0	0
GSK3B	-0.022	0.024	-10000	0	-10000	0	0
PAK1/Aurora A	0.002	0.052	0.21	1	-10000	0	1
MDM2	0.023	0.002	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.097	0.075	0.12	428	-10000	0	428
TP53	0	0.051	-10000	0	-0.23	9	9
DLG7	-0.004	0.045	0.13	29	-10000	0	29
AURKAIP1	0.022	0.004	-10000	0	-10000	0	0
ARHGEF7	0.022	0.005	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.039	0.097	0.24	73	-10000	0	73
G2/M transition of mitotic cell cycle	0	0.044	-10000	0	-0.16	1	1
AURKA	0.001	0.062	0.18	29	-10000	0	29
AURKB	0.12	0.074	0.16	374	-0.29	3	377
CDC25B	0.004	0.044	0.21	1	-0.17	2	3
G2/M transition checkpoint	-0.008	0.032	0.12	2	-0.13	3	5
mRNA polyadenylation	-0.077	0.1	-10000	0	-0.19	208	208
Aurora A/CPEB	-0.078	0.1	-10000	0	-0.2	208	208
Aurora A/TACC1/TRAP/chTOG	-0.018	0.085	-10000	0	-0.2	51	51
BRCA1	0.022	0.006	-10000	0	-10000	0	0
centrosome duplication	0.002	0.052	0.21	1	-10000	0	1
regulation of centrosome cycle	0.036	0.089	0.22	73	-10000	0	73
spindle assembly	-0.018	0.083	-10000	0	-0.2	51	51
TDRD7	0.022	0.006	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.13	0.095	0.23	146	-0.18	4	150
CENPA	0.13	0.072	0.17	373	-0.28	3	376
Aurora A/PP2A	0.002	0.053	0.21	1	-0.18	1	2
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.003	0.051	0.25	9	-10000	0	9
negative regulation of DNA binding	0	0.052	-10000	0	-0.23	10	10
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.031	0.01	-10000	0	-10000	0	0
RASA1	0.019	0.036	-10000	0	-0.35	5	5
Ajuba/Aurora A	-0.008	0.032	0.12	2	-0.13	3	5
mitotic prometaphase	-0.023	0.031	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.062	0.18	29	-10000	0	29
TACC1	-0.037	0.13	-10000	0	-0.35	83	83
TACC3	0.084	0.11	0.29	126	-10000	0	126
Aurora A/Antizyme1	0.005	0.053	-10000	0	-10000	0	0
Aurora A/RasGAP	0.001	0.056	0.21	1	-0.23	5	6
OAZ1	0.021	0.006	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.021	0.024	-10000	0	-10000	0	0
GIT1	0.022	0.005	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.042	0.015	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.097	0.075	0.12	428	-10000	0	428
PPP2R5D	0.023	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	0.077	0.074	0.24	60	-10000	0	60
PAK1	0.022	0.004	-10000	0	-10000	0	0
CKAP5	0.022	0.005	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	-0.005	0.013	0.29	1	-10000	0	1
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.032	0.019	0.21	5	-10000	0	5
STXBP1	-0.004	0.095	-10000	0	-0.35	38	38
ACh/CHRNA1	0.044	0.11	0.18	188	-0.13	12	200
RAB3GAP2/RIMS1/UNC13B	0.037	0.024	0.21	4	-10000	0	4
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	0.023	0.026	0.29	5	-10000	0	5
mol:ACh	-0.046	0.058	0.087	21	-0.1	241	262
RAB3GAP2	0.02	0.008	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.044	0.095	-10000	0	-0.24	40	40
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.043	0.11	0.18	188	-0.13	12	200
UNC13B	0.022	0.005	-10000	0	-10000	0	0
CHRNA1	0.11	0.12	0.28	191	-10000	0	191
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.073	0.11	-10000	0	-0.25	127	127
SNAP25	-0.1	0.12	-10000	0	-0.23	243	243
VAMP2	0.003	0.001	-10000	0	-10000	0	0
SYT1	-0.058	0.15	-10000	0	-0.35	117	117
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.003	0.058	0.22	1	-0.2	38	39
STX1A/SNAP25 fragment 1/VAMP2	-0.044	0.095	-10000	0	-0.24	40	40

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.046	0.14	-10000	0	-0.25	131	131
FZD6	0.02	0.018	-10000	0	-0.35	1	1
WNT6	0.01	0.11	0.28	23	-0.35	34	57
WNT4	-0.065	0.16	-10000	0	-0.35	126	126
FZD3	0.02	0.008	-10000	0	-10000	0	0
WNT5A	0.011	0.065	-10000	0	-0.35	17	17
WNT11	0.037	0.098	0.28	49	-0.35	14	63

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.079	0.28	0.35	4	-0.81	66	70
MKNK1	0.023	0.004	-10000	0	-10000	0	0
MAPK14	-0.005	0.1	-10000	0	-0.28	63	63
ATF2/c-Jun	-0.025	0.1	-10000	0	-0.37	21	21
MAPK11	-0.005	0.1	-10000	0	-0.29	57	57
MITF	-0.04	0.15	-10000	0	-0.34	91	91
MAPKAPK5	-0.019	0.12	-10000	0	-0.33	63	63
KRT8	-0.009	0.12	0.24	2	-0.33	62	64
MAPKAPK3	0.022	0.005	-10000	0	-10000	0	0
MAPKAPK2	0.02	0.008	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.01	0.15	-10000	0	-0.39	64	64
CEBPB	-0.015	0.11	0.25	1	-0.33	57	58
SLC9A1	-0.018	0.11	-10000	0	-0.33	61	61
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.02	0.12	-10000	0	-0.33	65	65
p38alpha-beta/MNK1	0.008	0.12	-10000	0	-0.32	60	60
JUN	-0.026	0.1	-10000	0	-0.37	21	21
PPARGC1A	-0.073	0.17	-10000	0	-0.32	144	144
USF1	-0.017	0.11	0.27	5	-0.33	58	63
RAB5/GDP/GDI1	-0.013	0.091	-10000	0	-0.24	60	60
NOS2	-0.02	0.15	-10000	0	-0.63	15	15
DDIT3	-0.019	0.12	-10000	0	-0.33	64	64
RAB5A	0.022	0.004	-10000	0	-10000	0	0
HSPB1	-0.019	0.097	0.28	6	-0.27	60	66
p38alpha-beta/HBP1	0.006	0.12	-10000	0	-0.31	63	63
CREB1	-0.021	0.13	-10000	0	-0.36	62	62
RAB5/GDP	0.017	0.003	-10000	0	-10000	0	0
EIF4E	-0.018	0.1	0.19	2	-0.31	50	52
RPS6KA4	-0.019	0.12	-10000	0	-0.33	63	63
PLA2G4A	-0.025	0.11	0.22	4	-0.31	62	66
GDI1	-0.018	0.12	-10000	0	-0.33	62	62
TP53	-0.029	0.13	-10000	0	-0.41	54	54
RPS6KA5	-0.02	0.12	-10000	0	-0.33	64	64
ESR1	-0.042	0.15	-10000	0	-0.35	90	90
HBP1	0.022	0.004	-10000	0	-10000	0	0
MEF2C	-0.04	0.15	-10000	0	-0.35	89	89
MEF2A	-0.022	0.12	-10000	0	-0.34	68	68
EIF4EBP1	-0.022	0.13	-10000	0	-0.37	61	61
KRT19	-0.017	0.12	0.21	1	-0.33	61	62
ELK4	-0.017	0.11	0.27	6	-0.32	60	66
ATF6	-0.017	0.11	0.27	5	-0.33	58	63
ATF1	-0.021	0.12	-10000	0	-0.36	62	62
p38alpha-beta/MAPKAPK2	0	0.12	-10000	0	-0.31	63	63
p38alpha-beta/MAPKAPK3	0.007	0.12	-10000	0	-0.31	62	62

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.023	0.002	-10000	0	-10000	0	0
PTK2	0.021	0.007	-10000	0	-10000	0	0
CRKL	-0.055	0.095	0.16	1	-0.24	101	102
GRB2/SOS1/SHC	0.035	0.021	-10000	0	-10000	0	0
HRAS	0.022	0.005	-10000	0	-10000	0	0
IRS1/Crk	-0.036	0.11	-10000	0	-0.24	103	103
IGF-1R heterotetramer/IGF1/PTP1B	-0.008	0.11	-10000	0	-0.23	97	97
AKT1	-0.039	0.099	0.16	33	-0.31	32	65
BAD	-0.04	0.093	0.15	32	-0.29	32	64
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.054	0.095	0.16	1	-0.24	96	97
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.032	0.11	0.2	2	-0.24	108	110
RAF1	-0.027	0.1	0.28	2	-0.4	14	16
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.01	0.12	-10000	0	-0.23	102	102
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.033	0.12	-10000	0	-0.23	130	130
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
RPS6KB1	-0.04	0.097	0.16	31	-0.31	32	63
GNB2L1	0.023	0.004	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.018	0.095	0.28	5	-0.34	8	13
PXN	0.023	0.003	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.032	0.009	-10000	0	-10000	0	0
HRAS/GTP	-0.02	0.088	-10000	0	-0.21	76	76
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.014	0.09	-10000	0	-0.19	76	76
IGF-1R heterotetramer	-0.01	0.084	-10000	0	-0.4	19	19
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.021	0.12	-10000	0	-0.24	108	108
Crk/p130 Cas/Paxillin	-0.013	0.11	0.2	1	-0.22	98	99
IGF1R	-0.01	0.084	-10000	0	-0.4	19	19
IGF1	-0.055	0.16	-10000	0	-0.38	99	99
IRS2/Crk	-0.055	0.12	0.15	1	-0.23	147	148
PI3K	-0.01	0.11	-10000	0	-0.23	93	93
apoptosis	0.034	0.083	0.26	30	-0.22	2	32
HRAS/GDP	0.016	0.004	-10000	0	-10000	0	0
PRKCD	-0.056	0.13	-10000	0	-0.32	102	102
RAF1/14-3-3 E	-0.011	0.1	0.28	2	-0.36	13	15
BAD/14-3-3	-0.036	0.087	0.22	2	-0.28	30	32
PRKCZ	-0.037	0.099	0.16	36	-0.31	32	68
Crk/p130 Cas/Paxillin/FAK1	-0.013	0.09	-10000	0	-0.29	30	30
PTPN1	0.022	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.058	0.14	-10000	0	-0.33	106	106
BCAR1	0.021	0.007	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.006	0.093	-10000	0	-0.2	80	80
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.023	0.003	-10000	0	-10000	0	0
IRS1/NCK2	-0.032	0.11	-10000	0	-0.23	108	108
GRB10	0.022	0.017	-10000	0	-0.35	1	1
PTPN11	-0.058	0.096	0.16	1	-0.23	108	109
IRS1	-0.04	0.11	0.12	7	-0.25	105	112
IRS2	-0.076	0.12	0.16	1	-0.24	149	150
IGF-1R heterotetramer/IGF1	-0.037	0.14	-10000	0	-0.3	107	107
GRB2	0.022	0.006	-10000	0	-10000	0	0
PDPK1	-0.04	0.1	0.17	33	-0.23	79	112
YWHAE	0.021	0.007	-10000	0	-10000	0	0
PRKD1	-0.068	0.15	-10000	0	-0.33	110	110
SHC1	0.019	0.009	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.016	0.037	-10000	0	-0.2	20	20
ADCY5	-0.045	0.076	-10000	0	-0.2	101	101
ADCY6	-0.009	0.002	-10000	0	-10000	0	0
ADCY7	-0.008	0.003	-10000	0	-10000	0	0
ADCY1	-0.014	0.038	0.24	1	-0.2	18	19
ADCY2	-0.11	0.098	-10000	0	-0.2	280	280
ADCY3	-0.01	0.012	-10000	0	-0.2	2	2
ADCY8	-0.009	0.016	0.24	2	-10000	0	2
PRKCE	-0.006	0.001	-10000	0	-10000	0	0
ADCY9	-0.035	0.067	-10000	0	-0.2	73	73
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.052	0.094	0.21	20	-0.17	105	125

×

TCGA08_p53

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
CDKN2A	0.042	0.062	0.11	216	-10000	0	216
TP53	0.003	0.047	-10000	0	-0.15	43	43
Senescence	0.003	0.047	-10000	0	-0.15	43	43
Apoptosis	0.003	0.047	-10000	0	-0.15	43	43
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.033	0.047	0.27	5	-0.2	7	12
MDM4	0.019	0.009	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.022	0.005	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.057	0.081	-10000	0	-0.23	39	39
NT3 (dimer)/TRKC	-0.11	0.15	0.21	3	-0.26	254	257
NT3 (dimer)/TRKB	-0.068	0.15	0.2	7	-0.24	212	219
SHC/Grb2/SOS1/GAB1/PI3K	0.011	0.03	-10000	0	-0.19	4	4
RAPGEF1	0.022	0.006	-10000	0	-10000	0	0
BDNF	0.062	0.094	0.28	84	-10000	0	84
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
DYNLT1	0.023	0.004	-10000	0	-10000	0	0
NTRK1	0.019	0.044	0.28	7	-0.35	4	11
NTRK2	-0.01	0.12	0.28	8	-0.35	52	60
NTRK3	-0.15	0.18	-10000	0	-0.35	251	251
NT-4/5 (dimer)/TRKB	-0.055	0.14	0.2	20	-0.23	202	222
neuron apoptosis	0.11	0.19	0.39	127	-10000	0	127
SHC 2-3/Grb2	-0.12	0.21	-10000	0	-0.42	128	128
SHC1	0.019	0.009	-10000	0	-10000	0	0
SHC2	-0.15	0.24	-10000	0	-0.5	140	140
SHC3	-0.092	0.18	0.22	1	-0.41	92	93
STAT3 (dimer)	0.026	0.014	0.22	2	-10000	0	2
NT3 (dimer)/TRKA	-0.041	0.12	0.2	6	-0.22	156	162
RIN/GDP	-0.043	0.1	0.24	3	-0.24	38	41
GIPC1	0.022	0.006	-10000	0	-10000	0	0
KRAS	0.023	0.014	0.33	1	-10000	0	1
DNAJA3	-0.099	0.15	0.22	2	-0.28	182	184
RIN/GTP	0.013	0.003	-10000	0	-10000	0	0
CCND1	0.013	0.027	0.36	3	-10000	0	3
MAGED1	0.021	0.023	-10000	0	-0.35	2	2
PTPN11	0.023	0.003	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.032	0.055	0.28	23	-0.35	1	24
SHC/GRB2/SOS1	0.035	0.021	-10000	0	-10000	0	0
GRB2	0.022	0.006	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.014	0.1	0.2	5	-0.21	108	113
TRKA/NEDD4-2	0.026	0.035	0.21	6	-0.25	5	11
ELMO1	0.02	0.032	-10000	0	-0.35	4	4
RhoG/GTP/ELMO1/DOCK1	0.024	0.036	-10000	0	-0.22	10	10
NGF	-0.056	0.15	-10000	0	-0.35	113	113
HRAS	0.022	0.005	-10000	0	-10000	0	0
DOCK1	0.017	0.042	-10000	0	-0.35	7	7
GAB2	0.02	0.032	-10000	0	-0.35	4	4
RIT2	0.017	0.005	-10000	0	-10000	0	0
RIT1	0.018	0.01	-10000	0	-10000	0	0
FRS2	0.023	0.003	-10000	0	-10000	0	0
DNM1	0.018	0.039	-10000	0	-0.35	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.086	0.16	0.18	1	-0.28	180	181
mol:GDP	-0.067	0.14	0.26	5	-0.33	48	53
NGF (dimer)	-0.055	0.15	-10000	0	-0.35	113	113
RhoG/GDP	0.015	0.022	-10000	0	-0.24	4	4
RIT1/GDP	-0.048	0.085	0.22	2	-0.24	32	34
TIAM1	0.014	0.057	-10000	0	-0.35	13	13
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
BDNF (dimer)/TRKB	0.042	0.1	0.2	83	-0.21	51	134
KIDINS220/CRKL/C3G	0.031	0.01	-10000	0	-10000	0	0
SHC/RasGAP	0.024	0.03	-10000	0	-0.25	5	5
FRS2 family/SHP2	0.045	0.01	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.042	0.032	-10000	0	-0.18	3	3
RIT1/GTP	0.013	0.007	-10000	0	-10000	0	0
NT3 (dimer)	0.002	0.092	0.28	5	-0.35	32	37
RAP1/GDP	-0.041	0.083	-10000	0	-0.2	39	39
KIDINS220/CRKL	0.022	0.005	-10000	0	-10000	0	0
BDNF (dimer)	0.062	0.093	0.28	84	-10000	0	84
ubiquitin-dependent protein catabolic process	-0.009	0.099	0.2	5	-0.21	100	105
Schwann cell development	-0.035	0.029	-10000	0	-10000	0	0
EHD4	0.022	0.005	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.053	0.019	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.006	0.059	-10000	0	-0.24	21	21
RAP1B	0.023	0.002	-10000	0	-10000	0	0
RAP1A	0.023	0.002	-10000	0	-10000	0	0
CDC42/GTP	-0.072	0.14	0.18	2	-0.2	254	256
ABL1	0.02	0.023	-10000	0	-0.35	2	2
SH2B family/GRB2/SOS1	0.032	0.009	-10000	0	-10000	0	0
Rap1/GTP	0.003	0.079	-10000	0	-0.28	16	16
STAT3	0.026	0.014	0.22	2	-10000	0	2
axon guidance	-0.076	0.13	-10000	0	-0.19	257	257
MAPK3	-0.021	0.1	0.18	72	-0.19	101	173
MAPK1	-0.021	0.11	0.18	72	-0.19	102	174
CDC42/GDP	-0.042	0.099	0.21	6	-0.24	34	40
NTF3	0.002	0.092	0.28	5	-0.35	32	37
NTF4	0.032	0.055	0.28	23	-0.35	1	24
NGF (dimer)/TRKA/FAIM	-0.008	0.098	0.2	5	-0.21	98	103
PI3K	0.027	0.029	-10000	0	-0.25	5	5
FRS3	0.023	0.003	-10000	0	-10000	0	0
FAIM	0.022	0.017	-10000	0	-0.35	1	1
GAB1	0.02	0.032	-10000	0	-0.35	4	4
RASGRF1	-0.11	0.16	0.22	2	-0.3	187	189
SOS1	0.023	0.003	-10000	0	-10000	0	0
MCF2L	-0.11	0.11	-10000	0	-0.23	243	243
RGS19	0.022	0.006	-10000	0	-10000	0	0
CDC42	0.022	0.005	-10000	0	-10000	0	0
RAS family/GTP	-0.01	0.096	-10000	0	-0.38	11	11
Rac1/GDP	-0.043	0.099	0.21	5	-0.24	36	41
NGF (dimer)/TRKA/GRIT	-0.017	0.092	0.19	5	-0.2	101	106
neuron projection morphogenesis	-0.12	0.24	-10000	0	-0.6	73	73
NGF (dimer)/TRKA/NEDD4-2	-0.009	0.099	0.2	5	-0.21	100	105
MAP2K1	0.026	0.086	0.18	117	-0.18	2	119
NGFR	-0.099	0.17	0.28	1	-0.35	174	175
NGF (dimer)/TRKA/GIPC/GAIP	-0.021	0.08	-10000	0	-0.2	88	88
RAS family/GTP/PI3K	0.013	0.027	0.17	1	-0.2	7	8
FRS2 family/SHP2/GRB2/SOS1	0.061	0.022	-10000	0	-10000	0	0
NRAS	0.023	0.001	-10000	0	-10000	0	0
GRB2/SOS1	0.032	0.009	-10000	0	-10000	0	0
PRKCI	0.021	0.007	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCZ	0.022	0.02	0.28	1	-0.35	1	2
MAPKKK cascade	-0.13	0.25	-10000	0	-0.57	120	120
RASA1	0.019	0.036	-10000	0	-0.35	5	5
TRKA/c-Abl	0.025	0.037	0.21	6	-0.24	6	12
SQSTM1	0.022	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.052	0.096	0.21	82	-0.19	47	129
NGF (dimer)/TRKA/p62/Atypical PKCs	0.008	0.09	-10000	0	-0.18	88	88
MATK	0.013	0.056	0.28	1	-0.35	12	13
NEDD4L	0.021	0.017	-10000	0	-0.35	1	1
RAS family/GDP	-0.052	0.06	-10000	0	-0.18	43	43
NGF (dimer)/TRKA	-0.1	0.15	0.19	1	-0.29	185	186
Rac1/GTP	-0.1	0.11	-10000	0	-0.24	175	175
FRS2 family/SHP2/CRK family	0.06	0.024	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.02	0.028	-10000	0	-0.35	3	3
EPHB2	0.025	0.02	0.28	3	-10000	0	3
EFNB1	-0.007	0.033	-10000	0	-0.28	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.024	0.077	-10000	0	-0.18	61	61
Ephrin B2/EPHB1-2	0.02	0.069	0.19	3	-0.18	53	56
neuron projection morphogenesis	0.012	0.068	-10000	0	-0.17	61	61
Ephrin B1/EPHB1-2/Tiam1	0.019	0.079	0.2	3	-0.18	64	67
DNM1	0.019	0.039	-10000	0	-0.35	6	6
cell-cell signaling	0.001	0.004	-10000	0	-10000	0	0
MAP2K4	-0.071	0.18	0.22	4	-0.48	82	86
YES1	-0.095	0.26	-10000	0	-0.7	82	82
Ephrin B1/EPHB1-2/NCK2	0.025	0.072	0.2	2	-0.18	54	56
PI3K	-0.046	0.19	-10000	0	-0.49	79	79
mol:GDP	0.018	0.078	0.2	2	-0.18	64	66
ITGA2B	0.018	0.041	0.28	1	-0.35	6	7
endothelial cell proliferation	0.027	0.019	-10000	0	-0.2	3	3
FYN	-0.094	0.26	-10000	0	-0.7	82	82
MAP3K7	-0.075	0.19	0.23	1	-0.51	81	82
FGR	-0.094	0.26	-10000	0	-0.7	81	81
TIAM1	0.014	0.057	-10000	0	-0.35	13	13
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
RGS3	0.022	0.006	-10000	0	-10000	0	0
cell adhesion	-0.078	0.19	0.25	1	-0.51	80	81
LYN	-0.094	0.26	-10000	0	-0.69	82	82
Ephrin B1/EPHB1-2/Src Family Kinases	-0.093	0.24	-10000	0	-0.64	84	84
Ephrin B1/EPHB1-2	-0.075	0.2	-10000	0	-0.56	77	77
SRC	-0.093	0.26	-10000	0	-0.69	82	82
ITGB3	-0.04	0.14	0.28	2	-0.35	90	92
EPHB1	-0.011	0.11	0.28	1	-0.35	50	51
EPHB4	0.022	0.004	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.028	0.02	-10000	0	-0.2	3	3
alphaIIb/beta3 Integrin	-0.016	0.11	0.21	3	-0.24	96	99
BLK	-0.088	0.26	-10000	0	-0.69	81	81
HCK	-0.09	0.25	-10000	0	-0.7	79	79
regulation of stress fiber formation	-0.023	0.071	0.18	54	-0.2	1	55
MAPK8	-0.068	0.17	0.22	2	-0.47	80	82
Ephrin B1/EPHB1-2/RGS3	0.024	0.072	0.2	4	-0.18	54	58
endothelial cell migration	-0.058	0.16	0.26	3	-0.44	74	77
NCK2	0.023	0.002	-10000	0	-10000	0	0
PTPN13	-0.039	0.16	-10000	0	-0.46	67	67
regulation of focal adhesion formation	-0.023	0.071	0.18	54	-0.2	1	55
chemotaxis	-0.022	0.071	0.18	54	-0.2	2	56
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
Rac1/GTP	0.019	0.073	-10000	0	-0.17	61	61
angiogenesis	-0.076	0.2	-10000	0	-0.55	79	79
LCK	-0.093	0.26	-10000	0	-0.69	82	82

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.081	0.12	-10000	0	-0.21	258	258
fibroblast growth factor receptor signaling pathway	-0.081	0.12	-10000	0	-0.21	258	258
LAMA1	0.1	0.13	0.28	174	-0.35	4	178
PRNP	-0.03	0.13	-10000	0	-0.35	76	76
GPC1/SLIT2	-0.002	0.091	-10000	0	-0.24	65	65
SMAD2	-0.016	0.032	0.18	6	-0.19	10	16
GPC1/PrPc/Cu2+	-0.004	0.082	-10000	0	-0.2	76	76
GPC1/Laminin alpha1	0.086	0.088	0.21	170	-0.25	4	174
TDGF1	0.014	0.091	0.28	17	-0.35	24	41
CRIPTO/GPC1	0.026	0.067	0.21	17	-0.24	24	41
APP/GPC1	0.033	0.007	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.018	0.042	-10000	0	-0.21	23	23
FLT1	0.022	0.005	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.038	0.036	-10000	0	-0.21	10	10
SERPINC1	0.022	0.034	0.29	8	-10000	0	8
FYN	-0.018	0.041	-10000	0	-0.21	22	22
FGR	-0.022	0.05	-10000	0	-0.21	32	32
positive regulation of MAPKKK cascade	0.01	0.089	0.24	32	-0.28	20	52
SLIT2	-0.023	0.12	-10000	0	-0.35	65	65
GPC1/NRG	0.025	0.038	0.21	1	-0.24	9	10
NRG1	0.014	0.049	0.28	1	-0.35	9	10
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.043	0.013	-10000	0	-10000	0	0
LYN	-0.017	0.04	-10000	0	-0.21	20	20
mol:Spermine	-0.006	0.001	-10000	0	-10000	0	0
cell growth	-0.081	0.12	-10000	0	-0.21	258	258
BMP signaling pathway	-0.023	0.003	-10000	0	-10000	0	0
SRC	-0.018	0.042	-10000	0	-0.21	23	23
TGFBR1	0.022	0.006	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.004	0.11	0.28	10	-0.35	43	53
GPC1	0.023	0.003	-10000	0	-10000	0	0
TGFBR1 (dimer)	0.022	0.006	-10000	0	-10000	0	0
VEGFA	0.023	0.003	-10000	0	-10000	0	0
BLK	-0.005	0.059	0.15	37	-0.21	19	56
HCK	-0.016	0.045	0.13	6	-0.21	22	28
FGF2	-0.17	0.19	-10000	0	-0.35	276	276
FGFR1	0.02	0.018	-10000	0	-0.35	1	1
VEGFR1 homodimer	0.022	0.005	-10000	0	-10000	0	0
TGFBR2	0.015	0.051	-10000	0	-0.35	10	10
cell death	0.033	0.007	-10000	0	-10000	0	0
ATIII/GPC1	0.03	0.026	0.22	8	-10000	0	8
PLA2G2A/GPC1	0.013	0.08	0.21	10	-0.24	43	53
LCK	-0.017	0.043	0.14	3	-0.21	22	25
neuron differentiation	0.025	0.038	0.21	1	-0.24	9	10
PrPc/Cu2+	-0.02	0.09	-10000	0	-0.24	76	76
APP	0.023	0.004	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.015	0.05	-10000	0	-0.35	10	10

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.09	0.26	0.48	6	-0.62	53	59
PCK1	-0.069	0.33	0.53	5	-1.1	37	42
HNF4A	-0.1	0.34	0.67	12	-0.78	67	79
KCNJ11	-0.081	0.27	0.6	5	-0.64	44	49
AKT1	-0.031	0.17	0.38	11	-0.36	23	34
response to starvation	-0.004	0.034	-10000	0	-0.16	5	5
DLK1	-0.13	0.34	0.61	8	-0.78	80	88
NKX2-1	-0.079	0.16	0.36	8	-0.36	58	66
ACADM	-0.094	0.27	0.5	5	-0.64	48	53
TAT	-0.078	0.23	0.54	3	-0.63	31	34
CEBPB	0.023	0.008	-10000	0	-10000	0	0
CEBPA	0.023	0.033	0.28	2	-0.35	3	5
TTR	0.071	0.18	0.55	12	-0.68	7	19
PKLR	-0.052	0.27	0.54	17	-0.63	34	51
APOA1	-0.16	0.44	0.68	10	-1.1	73	83
CPT1C	-0.094	0.27	0.5	5	-0.69	40	45
ALAS1	-0.044	0.17	0.46	3	-0.67	3	6
TFRC	-0.011	0.21	0.58	8	-0.58	10	18
FOXF1	0.017	0.036	-10000	0	-0.35	5	5
NF1	0.024	0.007	-10000	0	-10000	0	0
HNF1A (dimer)	0.04	0.043	0.31	8	-10000	0	8
CPT1A	-0.089	0.26	0.48	7	-0.63	45	52
HMGCS1	-0.086	0.26	0.52	6	-0.64	41	47
NR3C1	-0.051	0.14	-10000	0	-0.29	127	127
CPT1B	-0.088	0.26	0.54	6	-0.64	44	50
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.034	0.024	-10000	0	-10000	0	0
GCK	-0.15	0.35	0.58	5	-0.75	97	102
CREB1	0.017	0.056	-10000	0	-0.19	28	28
IGFBP1	-0.2	0.43	0.51	4	-1.1	87	91
PDX1	-0.008	0.18	0.49	11	-0.53	4	15
UCP2	-0.088	0.27	0.53	7	-0.65	41	48
ALDOB	-0.079	0.27	0.57	7	-0.66	37	44
AFP	0.068	0.073	0.35	5	-0.37	1	6
BDH1	-0.076	0.27	0.54	9	-0.64	40	49
HADH	-0.08	0.26	0.54	5	-0.67	33	38
F2	-0.099	0.34	0.67	13	-0.82	37	50
HNF1A	0.04	0.043	0.31	8	-10000	0	8
G6PC	0.028	0.072	0.4	1	-10000	0	1
SLC2A2	-0.027	0.19	0.6	5	-0.48	2	7
INS	0.006	0.069	0.2	37	-10000	0	37
FOXA1	0.19	0.14	0.29	342	-0.26	7	349
FOXA3	0.075	0.13	0.31	102	-0.27	10	112
FOXA2	-0.08	0.33	0.72	11	-0.72	46	57
ABCC8	-0.16	0.37	0.6	5	-0.8	106	111
ALB	0.061	0.12	0.38	3	-0.74	9	12

×

TCGA08_retinoblastoma

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
CDKN2B	0.018	0.045	0.29	9	-10000	0	9
CDKN2C	0.021	0.049	-10000	0	-0.34	9	9
CDKN2A	0.13	0.13	0.28	216	-10000	0	216
CCND2	-0.037	0.06	0.14	1	-0.16	55	56
RB1	0.035	0.067	0.31	14	-0.14	2	16
CDK4	-0.035	0.068	0.13	3	-0.32	14	17
CDK6	-0.04	0.073	0.16	1	-0.27	25	26
G1/S progression	-0.035	0.072	0.16	5	-0.32	15	20

×

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

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
MAP4K1	-0.047	0.13	0.2	1	-0.39	52	53
CRKL	-0.052	0.14	0.21	1	-0.37	70	71
HRAS	-0.035	0.12	-10000	0	-0.36	44	44
mol:PIP3	-0.02	0.15	0.26	5	-0.37	49	54
SPRED1	0.022	0.005	-10000	0	-10000	0	0
SPRED2	0.022	0.016	-10000	0	-0.35	1	1
GAB1	-0.054	0.15	-10000	0	-0.37	77	77
FOXO3	-0.035	0.14	0.3	3	-0.4	48	51
AKT1	-0.036	0.15	0.25	1	-0.43	49	50
BAD	-0.033	0.14	0.24	1	-0.4	46	47
megakaryocyte differentiation	-0.054	0.14	-10000	0	-0.36	77	77
GSK3B	-0.033	0.14	0.26	3	-0.4	47	50
RAF1	-0.017	0.12	0.24	6	-0.3	42	48
SHC1	0.019	0.009	-10000	0	-10000	0	0
STAT3	-0.052	0.14	-10000	0	-0.37	75	75
STAT1	-0.12	0.33	-10000	0	-0.82	82	82
HRAS/SPRED1	-0.01	0.12	0.23	1	-0.3	42	43
cell proliferation	-0.054	0.15	-10000	0	-0.36	77	77
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
TEC	0.023	0.012	0.28	1	-10000	0	1
RPS6KB1	-0.048	0.16	-10000	0	-0.44	61	61
HRAS/SPRED2	-0.01	0.12	0.23	1	-0.3	42	43
LYN/TEC/p62DOK	-0.019	0.15	-10000	0	-0.4	49	49
MAPK3	-0.012	0.096	0.21	8	-0.23	47	55
STAP1	-0.053	0.14	-10000	0	-0.36	80	80
GRAP2	0.011	0.061	-10000	0	-0.35	15	15
JAK2	-0.1	0.29	-10000	0	-0.71	83	83
STAT1 (dimer)	-0.12	0.32	-10000	0	-0.8	82	82
mol:Gleevec	0.002	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.02	0.15	-10000	0	-0.4	50	50
actin filament polymerization	-0.051	0.14	0.3	1	-0.35	76	77
LYN	0.021	0.007	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.083	0.22	-10000	0	-0.53	84	84
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
CBL/CRKL/GRB2	-0.03	0.14	-10000	0	-0.38	49	49
PI3K	-0.024	0.16	-10000	0	-0.43	51	51
PTEN	0.021	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.11	0.36	-10000	0	-1.1	52	52
MAPK8	-0.055	0.15	-10000	0	-0.37	77	77
STAT3 (dimer)	-0.051	0.14	0.26	1	-0.36	75	76
positive regulation of transcription	-0.008	0.082	0.19	9	-0.19	45	54
mol:GDP	-0.033	0.12	-10000	0	-0.37	44	44
PIK3C2B	-0.051	0.14	-10000	0	-0.36	72	72
CBL/CRKL	-0.041	0.14	-10000	0	-0.39	54	54
FER	-0.054	0.14	-10000	0	-0.36	77	77
SH2B3	-0.054	0.15	-10000	0	-0.37	76	76
PDPK1	-0.018	0.14	0.26	7	-0.36	45	52
SNAI2	-0.065	0.16	-10000	0	-0.39	81	81
positive regulation of cell proliferation	-0.095	0.26	-10000	0	-0.63	86	86
KITLG	-0.018	0.11	-10000	0	-0.37	48	48
cell motility	-0.095	0.26	-10000	0	-0.63	86	86
PTPN6	0.024	0.017	0.33	1	-10000	0	1
EPOR	-0.042	0.19	-10000	0	-0.83	15	15
STAT5A (dimer)	-0.082	0.22	0.28	1	-0.54	83	84
SOCS1	0.021	0.017	-10000	0	-0.35	1	1
cell migration	0.055	0.14	0.36	79	-10000	0	79
SOS1	0.023	0.003	-10000	0	-10000	0	0
EPO	0.002	0.067	0.28	1	-0.36	16	17
VAV1	0.023	0.03	0.28	5	-0.35	1	6
GRB10	-0.055	0.14	-10000	0	-0.37	74	74
PTPN11	0.024	0.009	-10000	0	-10000	0	0
SCF/KIT	-0.052	0.15	-10000	0	-0.37	81	81
GO:0007205	0.002	0.008	-10000	0	-10000	0	0
MAP2K1	-0.013	0.096	0.22	7	-0.24	40	47
CBL	0.022	0.005	-10000	0	-10000	0	0
KIT	-0.1	0.34	-10000	0	-1	55	55
MAP2K2	-0.011	0.093	0.22	7	-0.24	37	44
SHC/Grb2/SOS1	-0.022	0.14	-10000	0	-0.4	46	46
STAT5A	-0.083	0.23	-10000	0	-0.56	84	84
GRB2	0.022	0.006	-10000	0	-10000	0	0
response to radiation	-0.063	0.16	0.29	2	-0.38	81	83
SHC/GRAP2	0.021	0.04	-10000	0	-0.25	10	10
PTPRO	-0.055	0.15	-10000	0	-0.36	78	78
SH2B2	-0.053	0.14	-10000	0	-0.36	76	76
DOK1	0.023	0.003	-10000	0	-10000	0	0
MATK	-0.056	0.15	-10000	0	-0.36	79	79
CREBBP	0.012	0.052	-10000	0	-0.18	9	9
BCL2	-0.13	0.39	-10000	0	-1.1	69	69

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.011	0.1	-10000	0	-0.35	47	47
GNB1/GNG2	-0.034	0.14	-10000	0	-0.38	39	39
mol:DAG	-0.044	0.12	0.2	8	-0.36	37	45
PLCG1	-0.045	0.13	0.21	8	-0.37	37	45
YES1	-0.051	0.12	0.2	2	-0.4	33	35
FZD3	0.02	0.008	-10000	0	-10000	0	0
FZD6	0.02	0.018	-10000	0	-0.35	1	1
G protein	-0.031	0.14	0.25	3	-0.37	37	40
MAP3K7	-0.12	0.13	0.2	4	-0.31	115	119
mol:Ca2+	-0.043	0.12	0.2	8	-0.35	37	45
mol:IP3	-0.044	0.12	0.2	8	-0.36	37	45
NLK	-0.028	0.16	-10000	0	-0.82	20	20
GNB1	0.022	0.004	-10000	0	-10000	0	0
CAMK2A	-0.12	0.14	0.23	4	-0.32	115	119
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.046	0.14	-10000	0	-0.25	131	131
CSNK1A1	0.023	0.004	-10000	0	-10000	0	0
GNAS	-0.05	0.12	0.21	3	-0.38	36	39
GO:0007205	-0.047	0.12	0.21	9	-0.35	38	47
WNT6	0.01	0.11	0.28	23	-0.35	34	57
WNT4	-0.065	0.16	-10000	0	-0.35	126	126
NFAT1/CK1 alpha	-0.047	0.14	0.26	2	-0.36	45	47
GNG2	0.017	0.049	0.28	1	-0.35	9	10
WNT5A	0.011	0.065	-10000	0	-0.35	17	17
WNT11	0.037	0.098	0.28	49	-0.35	14	63
CDC42	-0.05	0.12	0.2	3	-0.39	31	34

×

Thromboxane A2 receptor signaling

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
TGM2	-0.013	0.11	-10000	0	-0.35	50	50
GNB1/GNG2	-0.044	0.073	-10000	0	-0.19	98	98
AKT1	-0.037	0.098	0.21	3	-0.24	42	45
EGF	0.031	0.055	0.28	21	-0.35	2	23
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.012	0.062	0.26	5	-0.26	2	7
mol:Ca2+	-0.066	0.14	0.25	2	-0.31	109	111
LYN	-0.01	0.054	0.27	4	-10000	0	4
RhoA/GTP	-0.027	0.057	-10000	0	-0.13	87	87
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.072	0.15	-10000	0	-0.35	98	98
GNG2	0.017	0.049	0.28	1	-0.35	9	10
ARRB2	0.021	0.006	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.051	0.18	-10000	0	-0.56	51	51
G beta5/gamma2	-0.054	0.098	-10000	0	-0.25	96	96
PRKCH	-0.076	0.16	-10000	0	-0.37	96	96
DNM1	0.018	0.039	-10000	0	-0.35	6	6
TXA2/TP beta/beta Arrestin3	0.012	0.026	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.01	0.1	-10000	0	-0.35	45	45
G12 family/GTP	-0.068	0.13	-10000	0	-0.3	103	103
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
ADRBK2	0.021	0.017	-10000	0	-0.35	1	1
RhoA/GTP/ROCK1	0.029	0.008	-10000	0	-10000	0	0
mol:GDP	0.048	0.13	0.41	37	-10000	0	37
mol:NADP	0.022	0.02	0.28	1	-0.35	1	2
RAB11A	0.022	0.005	-10000	0	-10000	0	0
PRKG1	-0.14	0.18	-10000	0	-0.35	226	226
mol:IP3	-0.085	0.18	-10000	0	-0.39	111	111
cell morphogenesis	0.029	0.008	-10000	0	-10000	0	0
PLCB2	-0.12	0.24	-10000	0	-0.54	110	110
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.002	0.07	0.3	9	-0.21	1	10
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.009	0.056	0.24	4	-0.22	1	5
RHOA	0.022	0.005	-10000	0	-10000	0	0
PTGIR	0.022	0.017	-10000	0	-0.35	1	1
PRKCB1	-0.081	0.17	-10000	0	-0.39	101	101
GNAQ	0.021	0.017	-10000	0	-0.35	1	1
mol:L-citrulline	0.022	0.02	0.28	1	-0.35	1	2
TXA2/TXA2-R family	-0.11	0.22	-10000	0	-0.54	98	98
LCK	-0.008	0.062	0.26	6	-0.22	1	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.011	0.055	-10000	0	-0.17	34	34
TXA2-R family/G12 family/GDP/G beta/gamma	-0.002	0.093	-10000	0	-0.42	22	22
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.013	0.053	-10000	0	-0.17	30	30
MAPK14	-0.047	0.1	0.21	1	-0.23	93	94
TGM2/GTP	-0.1	0.2	0.32	2	-0.44	121	123
MAPK11	-0.048	0.1	-10000	0	-0.23	97	97
ARHGEF1	-0.04	0.077	-10000	0	-0.18	93	93
GNAI2	0.022	0.005	-10000	0	-10000	0	0
JNK cascade	-0.08	0.17	-10000	0	-0.39	98	98
RAB11/GDP	0.022	0.005	-10000	0	-10000	0	0
ICAM1	-0.055	0.12	-10000	0	-0.28	96	96
cAMP biosynthetic process	-0.084	0.16	0.26	2	-0.36	122	124
Gq family/GTP/EBP50	-0.014	0.081	-10000	0	-0.26	35	35
actin cytoskeleton reorganization	0.029	0.008	-10000	0	-10000	0	0
SRC	-0.01	0.058	0.25	5	-0.22	1	6
GNB5	0.022	0.005	-10000	0	-10000	0	0
GNB1	0.022	0.004	-10000	0	-10000	0	0
EGF/EGFR	0.014	0.074	0.25	21	-0.23	4	25
VCAM1	-0.062	0.14	-10000	0	-0.32	98	98
TP beta/Gq family/GDP/G beta5/gamma2	-0.051	0.18	-10000	0	-0.56	51	51
platelet activation	-0.064	0.14	-10000	0	-0.31	98	98
PGI2/IP	0.016	0.011	-10000	0	-0.24	1	1
PRKACA	-0.003	0.055	-10000	0	-0.19	40	40
Gq family/GDP/G beta5/gamma2	-0.041	0.16	-10000	0	-0.48	48	48
TXA2/TP beta/beta Arrestin2	-0.003	0.071	-10000	0	-0.37	16	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.009	0.046	-10000	0	-0.18	35	35
mol:DAG	-0.093	0.19	-10000	0	-0.45	101	101
EGFR	0.014	0.059	0.33	1	-0.35	13	14
TXA2/TP alpha	-0.12	0.22	-10000	0	-0.49	122	122
Gq family/GTP	-0.027	0.092	-10000	0	-0.24	70	70
YES1	-0.008	0.059	0.26	6	-10000	0	6
GNAI2/GTP	0	0.049	-10000	0	-0.16	35	35
PGD2/DP	-0.005	0.071	-10000	0	-0.24	45	45
SLC9A3R1	0.024	0.023	0.28	4	-10000	0	4
FYN	-0.011	0.058	0.26	5	-0.22	1	6
mol:NO	0.022	0.02	0.28	1	-0.35	1	2
GNA15	0.025	0.03	0.28	7	-10000	0	7
PGK/cGMP	-0.07	0.12	-10000	0	-0.2	225	225
RhoA/GDP	0.022	0.005	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.006	0.086	-10000	0	-0.21	42	42
NOS3	0.022	0.02	0.28	1	-0.35	1	2
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCA	-0.079	0.16	-10000	0	-0.37	100	100
PRKCB	-0.081	0.16	-10000	0	-0.38	101	101
PRKCE	-0.074	0.16	0.28	1	-0.37	95	96
PRKCD	-0.079	0.17	-10000	0	-0.39	98	98
PRKCG	-0.082	0.17	0.28	1	-0.4	100	101
muscle contraction	-0.11	0.21	-10000	0	-0.5	102	102
PRKCZ	-0.073	0.15	0.25	1	-0.35	98	99
ARR3	0.019	0.012	0.28	1	-10000	0	1
TXA2/TP beta	0.011	0.057	-10000	0	-0.17	34	34
PRKCQ	-0.081	0.17	0.31	3	-0.38	104	107
MAPKKK cascade	-0.1	0.21	-10000	0	-0.48	106	106
SELE	-0.066	0.15	-10000	0	-0.35	96	96
TP beta/GNAI2/GDP/G beta/gamma	0.022	0.064	-10000	0	-0.18	35	35
ROCK1	0.023	0.004	-10000	0	-10000	0	0
GNA14	-0.01	0.1	-10000	0	-0.35	45	45
chemotaxis	-0.12	0.24	-10000	0	-0.6	98	98
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
GNA11	0.014	0.051	-10000	0	-0.35	10	10
Rac1/GTP	0.016	0.004	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.003	0.09	0.26	52	-0.21	12	64
KIRREL	-0.017	0.11	-10000	0	-0.36	54	54
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.003	0.091	0.22	12	-0.26	52	64
PLCG1	0.022	0.005	-10000	0	-10000	0	0
ARRB2	0.021	0.006	-10000	0	-10000	0	0
WASL	0.022	0.005	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.023	0.079	0.31	2	-0.19	50	52
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.006	0.07	0.2	3	-0.21	50	53
FYN	0.017	0.12	0.23	101	-0.18	51	152
mol:Ca2+	0.019	0.075	0.34	1	-0.19	51	52
mol:DAG	0.02	0.076	0.34	1	-0.19	51	52
NPHS2	-0.008	0.033	0.3	3	-10000	0	3
mol:IP3	0.02	0.076	0.34	1	-0.19	51	52
regulation of endocytosis	0.015	0.068	0.19	7	-0.17	51	58
Nephrin/NEPH1/podocin/Cholesterol	0.013	0.073	0.2	13	-0.19	52	65
establishment of cell polarity	0.003	0.09	0.21	12	-0.26	52	64
Nephrin/NEPH1/podocin/NCK1-2	0.029	0.08	0.31	2	-0.18	51	53
Nephrin/NEPH1/beta Arrestin2	0.016	0.069	0.2	7	-0.18	51	58
NPHS1	0.02	0.054	0.29	14	-10000	0	14
Nephrin/NEPH1/podocin	0.014	0.072	0.2	12	-0.18	51	63
TJP1	0.022	0.005	-10000	0	-10000	0	0
NCK1	0.021	0.023	-10000	0	-0.35	2	2
NCK2	0.023	0.002	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.021	0.077	0.35	1	-0.19	51	52
CD2AP	0.023	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.02	0.077	0.35	1	-0.19	51	52
GRB2	0.022	0.006	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.006	0.13	0.23	94	-0.2	67	161
cytoskeleton organization	-0.017	0.079	0.22	19	-0.22	49	68
Nephrin/NEPH1	0.007	0.064	0.18	12	-0.17	52	64
Nephrin/NEPH1/ZO-1	0.014	0.078	0.2	12	-0.2	52	64

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.003	0.081	0.2	1	-0.18	67	68
NF kappa B1 p50/RelA/I kappa B alpha	0	0.093	0.37	4	-0.26	4	8
alphaV/beta3 Integrin/Osteopontin/Src	0.084	0.08	0.21	148	-10000	0	148
AP1	-0.046	0.14	-10000	0	-0.33	56	56
ILK	-0.006	0.082	0.29	4	-0.21	2	6
bone resorption	-0.019	0.082	0.32	2	-0.31	6	8
PTK2B	0.02	0.008	-10000	0	-10000	0	0
PYK2/p130Cas	0.042	0.11	0.24	4	-0.17	58	62
ITGAV	0.024	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.024	0.047	-10000	0	-0.25	15	15
alphaV/beta3 Integrin/Osteopontin	0.045	0.13	0.21	125	-0.2	88	213
MAP3K1	-0.008	0.083	0.21	9	-0.18	85	94
JUN	0.018	0.043	-10000	0	-0.35	7	7
MAPK3	-0.022	0.071	0.22	9	-0.19	2	11
MAPK1	-0.023	0.072	0.21	9	-0.19	2	11
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
MAPK8	-0.026	0.074	0.21	9	-0.18	71	80
ITGB3	-0.038	0.14	0.28	2	-0.35	90	92
NFKBIA	-0.016	0.072	0.32	3	-0.22	2	5
FOS	-0.089	0.17	-10000	0	-0.35	160	160
CD44	0.019	0.042	0.33	1	-0.35	6	7
CHUK	0.022	0.005	-10000	0	-10000	0	0
PLAU	-0.026	0.1	0.47	2	-0.49	4	6
NF kappa B1 p50/RelA	0.018	0.083	0.31	3	-10000	0	3
BCAR1	0.021	0.007	-10000	0	-10000	0	0
RELA	0.022	0.004	-10000	0	-10000	0	0
alphaV beta3 Integrin	-0.01	0.1	0.21	2	-0.24	89	91
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.007	0.084	0.23	11	-0.18	84	95
VAV3	-0.012	0.083	0.25	11	-0.18	60	71
MAP3K14	-0.007	0.083	0.21	9	-0.18	75	84
ROCK2	0.015	0.051	-10000	0	-0.35	10	10
SPP1	0.097	0.12	0.28	153	-10000	0	153
RAC1	0.022	0.005	-10000	0	-10000	0	0
Rac1/GTP	0	0.079	0.23	11	-10000	0	11
MMP2	-0.071	0.12	0.29	1	-0.33	55	56

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	0.018	0.11	0.32	3	-0.19	95	98
SMAD6-7/SMURF1	0.041	0.023	-10000	0	-0.21	3	3
NOG	0.041	0.075	0.28	44	-0.35	2	46
SMAD9	-0.071	0.19	-10000	0	-0.49	86	86
SMAD4	0.022	0.005	-10000	0	-10000	0	0
SMAD5	-0.026	0.096	-10000	0	-0.33	26	26
BMP7/USAG1	0.021	0.11	0.22	54	-0.25	57	111
SMAD5/SKI	-0.021	0.11	-10000	0	-0.35	28	28
SMAD1	0.004	0.063	0.24	2	-0.46	5	7
BMP2	-0.009	0.1	-10000	0	-0.35	45	45
SMAD1/SMAD1/SMAD4	0.016	0.06	-10000	0	-0.32	6	6
BMPR1A	0.022	0.006	-10000	0	-10000	0	0
BMPR1B	0.002	0.086	0.28	1	-0.35	30	31
BMPR1A-1B/BAMBI	0.024	0.074	0.21	7	-0.22	40	47
AHSG	0.025	0.039	0.28	12	-10000	0	12
CER1	0.018	0.005	-10000	0	-10000	0	0
BMP2-4/CER1	0.015	0.085	0.2	8	-0.22	56	64
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.044	0.11	-10000	0	-0.33	41	41
BMP2-4 (homodimer)	0.002	0.098	0.21	8	-0.26	60	68
RGMB	0.022	0.017	-10000	0	-0.35	1	1
BMP6/BMPR2/BMPR1A-1B	0.036	0.066	-10000	0	-0.2	36	36
RGMA	-0.059	0.15	-10000	0	-0.35	117	117
SMURF1	0.023	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.042	0.1	-10000	0	-0.3	44	44
BMP2-4/USAG1	0.012	0.12	0.2	41	-0.23	84	125
SMAD6/SMURF1/SMAD5	-0.023	0.11	-10000	0	-0.35	29	29
SOSTDC1	0.018	0.11	0.28	38	-0.35	32	70
BMP7/BMPR2/BMPR1A-1B	0.035	0.082	0.21	20	-0.2	48	68
SKI	0.022	0.004	-10000	0	-10000	0	0
BMP6 (homodimer)	0.015	0.053	-10000	0	-0.35	11	11
HFE2	0.016	0.018	0.28	2	-10000	0	2
ZFYVE16	0.022	0.005	-10000	0	-10000	0	0
MAP3K7	0.023	0.003	-10000	0	-10000	0	0
BMP2-4/CHRD	-0.016	0.12	0.2	8	-0.23	113	121
SMAD5/SMAD5/SMAD4	-0.021	0.11	-10000	0	-0.35	29	29
MAPK1	0.022	0.005	-10000	0	-10000	0	0
TAK1/TAB family	-0.025	0.11	-10000	0	-0.28	43	43
BMP7 (homodimer)	0.017	0.11	0.29	30	-0.35	29	59
NUP214	0.022	0.006	-10000	0	-10000	0	0
BMP6/FETUA	0.027	0.049	0.21	12	-0.25	11	23
SMAD1/SKI	0.013	0.071	-10000	0	-0.41	6	6
SMAD6	0.021	0.017	-10000	0	-0.35	1	1
CTDSP2	0.023	0.001	-10000	0	-10000	0	0
BMP2-4/FETUA	0.021	0.083	0.2	17	-0.22	48	65
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.068	0.16	-10000	0	-0.35	129	129
BMPR2 (homodimer)	0.023	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.043	0.014	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.017	0.063	0.21	1	-0.25	28	29
CHRDL1	-0.23	0.17	-10000	0	-0.35	365	365
ENDOFIN/SMAD1	0.012	0.071	-10000	0	-0.4	6	6
SMAD6-7/SMURF1/SMAD1	0.029	0.075	-10000	0	-0.38	6	6
SMAD6/SMURF1	0.022	0.004	-10000	0	-10000	0	0
BAMBI	0.014	0.073	0.28	8	-0.35	17	25
SMURF2	0.022	0.006	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.15	0.14	0.2	2	-0.23	372	374
BMP2-4/GREM1	-0.042	0.14	0.2	7	-0.24	165	172
SMAD7	0.021	0.023	-10000	0	-0.35	2	2
SMAD8A/SMAD8A/SMAD4	-0.066	0.19	-10000	0	-0.46	92	92
SMAD1/SMAD6	0.011	0.073	-10000	0	-0.39	7	7
TAK1/SMAD6	0.033	0.007	-10000	0	-10000	0	0
BMP7	0.017	0.11	0.29	30	-0.35	29	59
BMP6	0.015	0.053	-10000	0	-0.35	11	11
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.037	0.11	-10000	0	-0.3	51	51
PPM1A	0.022	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.013	0.069	-10000	0	-0.41	6	6
SMAD7/SMURF1	0.031	0.019	-10000	0	-0.25	2	2
CTDSPL	0.022	0.004	-10000	0	-10000	0	0
PPP1CA	0.022	0.004	-10000	0	-10000	0	0
XIAP	0.023	0.001	-10000	0	-10000	0	0
CTDSP1	0.023	0.004	-10000	0	-10000	0	0
PPP1R15A	0.023	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.064	0.14	-10000	0	-0.38	65	65
CHRD	-0.036	0.13	-10000	0	-0.35	82	82
BMPR2	0.023	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.049	0.11	-10000	0	-0.33	41	41
BMP4	0.011	0.083	0.28	9	-0.35	23	32
FST	-0.016	0.12	0.28	6	-0.35	58	64
BMP2-4/NOG	0.026	0.1	0.21	43	-0.22	62	105
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.041	0.082	0.23	2	-0.19	48	50

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.061	0.094	0.32	62	-10000	0	62
NFATC2	0	0.17	-10000	0	-0.48	35	35
NFATC3	0.001	0.09	-10000	0	-0.27	37	37
CD40LG	-0.11	0.3	-10000	0	-0.8	64	64
ITCH	0.021	0.02	-10000	0	-0.2	1	1
CBLB	0.022	0.02	-10000	0	-0.2	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.045	0.25	0.44	13	-0.67	39	52
JUNB	0.018	0.036	-10000	0	-0.35	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.036	0.035	-10000	0	-0.24	1	1
T cell anergy	0.018	0.053	0.27	8	-0.33	1	9
TLE4	-0.03	0.18	-10000	0	-0.57	46	46
Jun/NFAT1-c-4/p21SNFT	-0.041	0.31	-10000	0	-0.76	65	65
AP-1/NFAT1-c-4	-0.072	0.38	0.59	3	-0.9	63	66
IKZF1	-0.004	0.12	0.34	1	-0.36	28	29
T-helper 2 cell differentiation	-0.065	0.21	-10000	0	-0.79	21	21
AP-1/NFAT1	-0.034	0.18	0.31	3	-0.36	65	68
CALM1	0.031	0.016	-10000	0	-0.15	1	1
EGR2	-0.11	0.37	-10000	0	-1.1	53	53
EGR3	-0.13	0.41	-10000	0	-1.1	73	73
NFAT1/FOXP3	0.045	0.17	0.42	33	-0.34	28	61
EGR1	-0.023	0.12	-10000	0	-0.35	68	68
JUN	0.018	0.047	-10000	0	-0.35	7	7
EGR4	0.03	0.043	0.28	15	-10000	0	15
mol:Ca2+	0.009	0.014	-10000	0	-0.14	1	1
GBP3	-0.007	0.12	-10000	0	-0.41	25	25
FOSL1	0.042	0.069	0.28	42	-10000	0	42
NFAT1-c-4/MAF/IRF4	-0.063	0.33	0.48	1	-0.8	69	70
DGKA	-0.002	0.11	-10000	0	-0.36	17	17
CREM	0.021	0.009	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.058	0.32	-10000	0	-0.78	72	72
CTLA4	0.023	0.13	0.3	53	-0.29	27	80
NFAT1-c-4 (dimer)/EGR1	-0.066	0.34	-10000	0	-0.82	72	72
NFAT1-c-4 (dimer)/EGR4	-0.039	0.32	0.5	1	-0.77	71	72
FOS	-0.087	0.17	-10000	0	-0.35	160	160
IFNG	-0.032	0.2	-10000	0	-0.72	20	20
T cell activation	-0.069	0.2	-10000	0	-0.61	39	39
MAF	-0.032	0.13	-10000	0	-0.35	76	76
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.066	0.28	0.71	69	-10000	0	69
TNF	-0.071	0.3	0.47	1	-0.75	69	70
FASLG	-0.15	0.45	-10000	0	-1.1	84	84
TBX21	0.026	0.058	0.35	3	-0.35	9	12
BATF3	0.02	0.014	0.28	1	-10000	0	1
PRKCQ	-0.005	0.1	0.32	1	-0.35	43	44
PTPN1	-0.004	0.11	-10000	0	-0.34	30	30
NFAT1-c-4/ICER1	-0.051	0.31	-10000	0	-0.77	71	71
GATA3	0.025	0.057	0.28	13	-0.35	6	19
T-helper 1 cell differentiation	-0.031	0.2	-10000	0	-0.71	20	20
IL2RA	-0.043	0.26	0.46	13	-0.64	46	59
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.004	0.11	-10000	0	-0.34	29	29
E2F1	0.074	0.1	0.29	100	-10000	0	100
PPARG	0.004	0.084	0.33	1	-0.35	28	29
SLC3A2	-0.003	0.11	-10000	0	-0.34	27	27
IRF4	0.02	0.061	0.28	9	-0.35	10	19
PTGS2	-0.12	0.31	0.41	1	-0.78	70	71
CSF2	-0.11	0.3	-10000	0	-0.78	64	64
JunB/Fra1/NFAT1-c-4	-0.031	0.31	0.48	1	-0.76	64	65
IL4	-0.067	0.22	-10000	0	-0.84	20	20
IL5	-0.11	0.29	-10000	0	-0.78	64	64
IL2	-0.071	0.2	-10000	0	-0.62	38	38
IL3	-0.021	0.11	-10000	0	-0.66	12	12
RNF128	0.031	0.059	0.22	42	-0.47	1	43
NFATC1	-0.067	0.28	-10000	0	-0.71	69	69
CDK4	0.062	0.19	0.58	35	-10000	0	35
PTPRK	-0.003	0.12	0.34	1	-0.35	28	29
IL8	-0.073	0.32	0.43	2	-0.79	63	65
POU2F1	0.019	0.009	-10000	0	-10000	0	0

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.065	0.16	-10000	0	-0.35	124	124
CDC42/GTP	-0.042	0.11	-10000	0	-0.2	129	129
PLCG1	-0.043	0.097	-10000	0	-0.21	116	116
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.002	-10000	0	-10000	0	0
G12/G13	0.031	0.01	-10000	0	-10000	0	0
cell migration	-0.042	0.1	-10000	0	-0.2	129	129
S1PR5	0.025	0.053	0.29	13	-0.35	4	17
S1PR4	0.02	0.026	0.28	1	-0.35	2	3
MAPK3	-0.045	0.099	-10000	0	-0.21	118	118
MAPK1	-0.041	0.098	-10000	0	-0.21	114	114
S1P/S1P5/Gi	-0.038	0.1	0.17	2	-0.22	113	115
GNAI1	0.017	0.045	-10000	0	-0.35	8	8
CDC42/GDP	0.017	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.03	0.029	0.19	10	-0.2	3	13
RHOA	-0.008	0.034	0.18	16	-0.17	2	18
S1P/S1P4/Gi	-0.039	0.1	-10000	0	-0.21	124	124
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.01	0.065	-10000	0	-0.35	17	17
S1P/S1P4/G12/G13	0.038	0.022	0.19	1	-0.18	2	3
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
CDC42	0.022	0.005	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.024	0.074	-10000	0	-0.18	62	62
ER alpha/Gai/GDP/Gbeta gamma	-0.11	0.21	-10000	0	-0.48	92	92
AKT1	-0.081	0.25	-10000	0	-0.72	69	69
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.08	0.26	-10000	0	-0.74	69	69
mol:Ca2+	-0.032	0.11	-10000	0	-0.36	49	49
IGF1R	0.009	0.069	-10000	0	-0.35	19	19
E2/ER alpha (dimer)/Striatin	0.005	0.072	-10000	0	-0.2	56	56
SHC1	0.019	0.009	-10000	0	-10000	0	0
apoptosis	0.077	0.24	0.69	69	-10000	0	69
RhoA/GTP	0.002	0.053	-10000	0	-0.16	48	48
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.075	0.18	-10000	0	-0.42	77	77
regulation of stress fiber formation	0.02	0.067	0.26	2	-0.25	11	13
E2/ERA-ERB (dimer)	0.005	0.072	0.19	1	-0.2	56	57
KRAS	0.023	0.014	0.33	1	-10000	0	1
G13/GTP	0.005	0.064	-10000	0	-0.18	55	55
pseudopodium formation	-0.02	0.067	0.25	11	-0.26	2	13
E2/ER alpha (dimer)/PELP1	0.004	0.07	-10000	0	-0.2	54	54
GRB2	0.022	0.006	-10000	0	-10000	0	0
GNG2	0.017	0.049	0.28	1	-0.35	9	10
GNAO1	-0.065	0.16	-10000	0	-0.35	124	124
HRAS	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.085	0.2	-10000	0	-0.5	77	77
E2/ER beta (dimer)	0.017	0.008	0.19	1	-10000	0	1
mol:GDP	-0.02	0.097	-10000	0	-0.3	54	54
mol:NADP	-0.085	0.2	-10000	0	-0.5	77	77
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
mol:IP3	-0.035	0.11	-10000	0	-0.37	49	49
IGF-1R heterotetramer	0.009	0.069	-10000	0	-0.35	19	19
PLCB1	-0.033	0.12	-10000	0	-0.38	52	52
PLCB2	-0.031	0.12	-10000	0	-0.37	51	51
IGF1	-0.046	0.14	-10000	0	-0.35	100	100
mol:L-citrulline	-0.085	0.2	-10000	0	-0.5	77	77
RHOA	0.022	0.005	-10000	0	-10000	0	0
Gai/GDP	-0.19	0.31	-10000	0	-0.62	180	180
JNK cascade	0.017	0.008	0.19	1	-10000	0	1
BCAR1	0.021	0.007	-10000	0	-10000	0	0
ESR2	0.023	0.012	0.28	1	-10000	0	1
GNAQ	0.021	0.017	-10000	0	-0.35	1	1
ESR1	-0.017	0.11	-10000	0	-0.35	56	56
Gq family/GDP/Gbeta gamma	-0.067	0.23	-10000	0	-0.65	62	62
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.019	0.12	-10000	0	-0.63	13	13
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.071	0.17	-10000	0	-0.43	69	69
GNAZ	0.01	0.065	-10000	0	-0.35	17	17
E2/ER alpha (dimer)	-0.011	0.079	-10000	0	-0.24	56	56
STRN	0.021	0.023	-10000	0	-0.35	2	2
GNAL	-0.031	0.13	-10000	0	-0.35	77	77
PELP1	0.021	0.006	-10000	0	-10000	0	0
MAPK11	0.008	0.013	-10000	0	-0.2	2	2
GNAI2	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.002	-10000	0	-10000	0	0
GNAI1	0.017	0.045	-10000	0	-0.35	8	8
HBEGF	-0.091	0.19	0.28	3	-0.49	67	70
cAMP biosynthetic process	-0.019	0.087	-10000	0	-0.18	113	113
SRC	-0.1	0.2	0.26	1	-0.47	83	84
PI3K	0.027	0.029	-10000	0	-0.25	5	5
GNB1	0.022	0.004	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.004	0.098	-10000	0	-0.28	48	48
SOS1	0.023	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.09	0.16	-10000	0	-0.38	91	91
Gs family/GTP	-0.015	0.091	0.15	1	-0.18	113	114
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.042	0.014	0.22	1	-10000	0	1
vasodilation	-0.08	0.18	-10000	0	-0.47	77	77
mol:DAG	-0.035	0.11	-10000	0	-0.37	49	49
Gs family/GDP/Gbeta gamma	-0.032	0.11	-10000	0	-0.3	54	54
MSN	-0.022	0.07	0.25	11	-0.28	2	13
Gq family/GTP	-0.026	0.12	-10000	0	-0.4	48	48
mol:PI-3-4-5-P3	-0.076	0.25	-10000	0	-0.7	70	70
NRAS	0.023	0.001	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.08	0.18	0.47	77	-10000	0	77
GRB2/SOS1	0.032	0.009	-10000	0	-10000	0	0
RhoA/GDP	-0.007	0.098	-10000	0	-0.3	49	49
NOS3	-0.09	0.21	-10000	0	-0.52	77	77
GNA11	0.014	0.051	-10000	0	-0.35	10	10
MAPKKK cascade	-0.069	0.2	-10000	0	-0.53	73	73
E2/ER alpha (dimer)/PELP1/Src	-0.081	0.18	0.25	1	-0.43	81	82
ruffle organization	-0.02	0.067	0.25	11	-0.26	2	13
ROCK2	-0.018	0.076	0.27	11	-0.3	2	13
GNA14	-0.01	0.1	-10000	0	-0.35	45	45
GNA15	0.025	0.03	0.28	7	-10000	0	7
GNA13	0.022	0.005	-10000	0	-10000	0	0
MMP9	-0.089	0.19	0.3	6	-0.47	71	77
MMP2	-0.1	0.19	0.25	2	-0.46	84	86

×

S1P1 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
VEGFR2 homodimer/VEGFA homodimer	0.014	0.067	-10000	0	-0.25	31	31
PDGFRB	0.006	0.072	-10000	0	-0.36	20	20
SPHK1	-0.018	0.12	-10000	0	-0.78	12	12
mol:S1P	-0.021	0.11	-10000	0	-0.68	12	12
S1P1/S1P/Gi	-0.1	0.19	0.24	1	-0.35	164	165
GNAO1	-0.069	0.16	-10000	0	-0.35	124	124
PDGFB-D/PDGFRB/PLCgamma1	-0.086	0.18	0.28	4	-0.4	98	102
PLCG1	-0.098	0.18	0.27	3	-0.41	97	100
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.006	0.072	-10000	0	-0.36	20	20
GNAI2	0.018	0.016	-10000	0	-10000	0	0
GNAI3	0.018	0.015	-10000	0	-10000	0	0
GNAI1	0.012	0.048	-10000	0	-0.36	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.018	0.047	-10000	0	-0.2	31	31
S1P1/S1P	-0.027	0.095	0.22	2	-0.38	20	22
negative regulation of cAMP metabolic process	-0.1	0.19	0.24	1	-0.34	164	165
MAPK3	-0.12	0.22	0.25	4	-0.53	97	101
calcium-dependent phospholipase C activity	-0.001	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.004	-10000	0	-10000	0	0
KDR	-0.002	0.089	-10000	0	-0.35	32	32
PLCB2	-0.019	0.089	0.21	6	-0.34	18	24
RAC1	0.022	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.022	0.081	-10000	0	-0.32	20	20
receptor internalization	-0.027	0.087	-10000	0	-0.33	22	22
PTGS2	-0.15	0.32	0.37	1	-0.87	75	76
Rac1/GTP	-0.022	0.081	-10000	0	-0.32	20	20
RHOA	0.022	0.005	-10000	0	-10000	0	0
VEGFA	0.02	0.011	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.1	0.19	0.24	1	-0.34	164	165
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.006	0.067	-10000	0	-0.36	17	17
MAPK1	-0.12	0.23	0.23	1	-0.54	95	96
S1P1/S1P/PDGFB-D/PDGFRB	-0.024	0.11	0.25	5	-0.33	33	38
ABCC1	0.018	0.014	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.091	0.2	-10000	0	-0.36	146	146
MAP3K8	0.01	0.033	-10000	0	-0.35	3	3
FOS	-0.061	0.16	-10000	0	-0.47	47	47
PRKCA	-0.012	0.087	-10000	0	-0.35	31	31
PTPN7	0.009	0.036	0.26	6	-10000	0	6
HRAS	0.021	0.005	-10000	0	-10000	0	0
PRKCB	-0.012	0.087	-10000	0	-0.35	31	31
NRAS	0.022	0.002	-10000	0	-10000	0	0
RAS family/GTP	0.022	0.034	0.22	1	-10000	0	1
MAPK3	-0.029	0.14	-10000	0	-0.66	17	17
MAP2K1	-0.059	0.15	-10000	0	-0.4	72	72
ELK1	0.006	0.027	-10000	0	-10000	0	0
BRAF	-0.04	0.13	-10000	0	-0.36	62	62
mol:GTP	-0.001	0.002	-10000	0	-0.005	165	165
MAPK1	-0.036	0.14	-10000	0	-0.55	27	27
RAF1	-0.041	0.13	-10000	0	-0.38	60	60
KRAS	0.022	0.014	0.33	1	-10000	0	1

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.022	0.017	-10000	0	-0.35	1	1
CCL5	0.021	0.045	0.28	6	-0.35	5	11
SDCBP	0.021	0.007	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.071	0.09	0.25	35	-0.26	3	38
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	0.064	0.089	0.24	22	-0.26	5	27
Syndecan-1/Syntenin	0.065	0.089	0.25	17	-0.28	4	21
MAPK3	0.052	0.081	0.23	15	-0.26	4	19
HGF/MET	-0.022	0.12	0.21	4	-0.25	106	110
TGFB1/TGF beta receptor Type II	0.022	0.017	-10000	0	-0.35	1	1
BSG	0.021	0.006	-10000	0	-10000	0	0
keratinocyte migration	0.063	0.089	0.24	22	-0.26	5	27
Syndecan-1/RANTES	0.07	0.092	0.25	25	-0.31	5	30
Syndecan-1/CD147	0.071	0.091	0.26	13	-0.27	4	17
Syndecan-1/Syntenin/PIP2	0.061	0.084	0.25	13	-0.27	4	17
LAMA5	0.022	0.015	0.33	1	-10000	0	1
positive regulation of cell-cell adhesion	0.059	0.082	0.24	12	-0.26	4	16
MMP7	0.027	0.13	0.28	62	-0.35	36	98
HGF	-0.05	0.15	-10000	0	-0.35	104	104
Syndecan-1/CASK	0.055	0.087	0.2	34	-0.24	8	42
Syndecan-1/HGF/MET	0.043	0.13	0.27	17	-0.29	27	44
regulation of cell adhesion	0.044	0.075	0.23	11	-0.28	2	13
HPSE	0.016	0.053	0.28	2	-0.35	10	12
positive regulation of cell migration	0.071	0.09	0.25	35	-0.26	3	38
SDC1	0.072	0.088	0.24	34	-0.3	2	36
Syndecan-1/Collagen	0.071	0.09	0.25	35	-0.26	3	38
PPIB	0.023	0.012	0.28	1	-10000	0	1
MET	0.021	0.042	0.28	4	-0.35	5	9
PRKACA	0.022	0.005	-10000	0	-10000	0	0
MMP9	0.13	0.13	0.28	220	-10000	0	220
MAPK1	0.053	0.079	0.23	10	-0.25	4	14
homophilic cell adhesion	0.07	0.093	0.25	36	-0.27	3	39
MMP1	0.16	0.13	0.28	281	-10000	0	281

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	0.033	0.059	0.21	5	-0.21	22	27
alphaM/beta2 Integrin/GPIbA	0.042	0.043	0.26	6	-0.21	4	10
alphaM/beta2 Integrin/proMMP-9	0.11	0.093	0.22	209	-0.21	2	211
PLAUR	0.024	0.021	0.3	3	-10000	0	3
HMGB1	0.022	0.015	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.044	0.038	0.24	6	-0.2	3	9
AGER	0.022	0.022	-10000	0	-0.35	1	1
RAP1A	0.023	0.002	-10000	0	-10000	0	0
SELPLG	0.024	0.016	0.28	2	-10000	0	2
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.061	0.065	0.33	2	-0.19	19	21
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.13	0.13	0.28	220	-10000	0	220
CYR61	-0.01	0.1	-10000	0	-0.35	47	47
TLN1	0.022	0.005	-10000	0	-10000	0	0
Rap1/GTP	-0.002	0.1	0.21	1	-0.31	28	29
RHOA	0.022	0.005	-10000	0	-10000	0	0
P-selectin oligomer	-0.096	0.17	-10000	0	-0.35	166	166
MYH2	-0.017	0.12	0.25	8	-0.44	21	29
MST1R	0.045	0.077	0.28	50	-0.35	1	51
leukocyte activation during inflammatory response	0.047	0.055	0.27	5	-0.17	10	15
APOB	0.017	0.047	0.3	3	-0.35	7	10
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.007	0.071	-10000	0	-0.35	20	20
JAM3	-0.072	0.16	-10000	0	-0.35	136	136
GP1BA	0.02	0.021	0.28	1	-0.35	1	2
alphaM/beta2 Integrin/CTGF	0.039	0.051	0.24	5	-0.2	15	20
alphaM/beta2 Integrin	-0.008	0.099	0.22	8	-0.34	21	29
JAM3 homodimer	-0.072	0.16	-10000	0	-0.35	136	136
ICAM2	0.022	0.005	-10000	0	-10000	0	0
ICAM1	0.024	0.025	0.3	4	-10000	0	4
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.007	0.1	0.22	8	-0.34	23	31
cell adhesion	0.042	0.042	0.26	6	-0.21	4	10
NFKB1	0.024	0.088	0.3	10	-0.32	16	26
THY1	0.022	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.004	-10000	0	-10000	0	0
Lipoprotein(a)	0.033	0.048	0.19	31	-0.2	7	38
alphaM/beta2 Integrin/LRP/tPA	0.029	0.077	0.23	1	-0.19	49	50
IL6	-0.005	0.12	0.29	10	-0.58	16	26
ITGB2	0.025	0.029	0.28	5	-10000	0	5
elevation of cytosolic calcium ion concentration	0.053	0.042	0.23	12	-0.19	2	14
alphaM/beta2 Integrin/JAM2/JAM3	-0.075	0.16	0.28	2	-0.24	233	235
JAM2	-0.1	0.18	-10000	0	-0.35	184	184
alphaM/beta2 Integrin/ICAM1	0.074	0.064	0.27	11	-0.17	3	14
alphaM/beta2 Integrin/uPA/Plg	0.04	0.076	0.28	5	-0.18	38	43
RhoA/GTP	-0.021	0.13	0.24	8	-0.44	27	35
positive regulation of phagocytosis	0.007	0.083	0.3	4	-0.28	11	15
Ron/MSP	0.05	0.055	0.21	55	-0.25	1	56
alphaM/beta2 Integrin/uPAR/uPA	0.055	0.043	0.23	12	-0.19	2	14
alphaM/beta2 Integrin/uPAR	0.046	0.04	0.23	9	-0.2	3	12
PLAU	0.023	0.02	0.28	3	-10000	0	3
PLAT	-0.014	0.11	-10000	0	-0.35	49	49
actin filament polymerization	-0.017	0.12	0.26	8	-0.41	23	31
MST1	0.025	0.027	0.28	6	-10000	0	6
alphaM/beta2 Integrin/lipoprotein(a)	0.052	0.059	0.29	5	-0.18	10	15
TNF	0.008	0.1	0.33	10	-0.36	12	22
RAP1B	0.023	0.002	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.045	0.038	0.23	9	-0.21	2	11
fibrinolysis	0.038	0.074	0.28	5	-0.18	38	43
HCK	0.025	0.03	0.28	7	-10000	0	7
dendritic cell antigen processing and presentation	-0.007	0.1	0.22	8	-0.34	23	31
VTN	-0.022	0.12	0.3	3	-0.35	65	68
alphaM/beta2 Integrin/CYR61	0.023	0.079	0.21	5	-0.21	48	53
LPA	0.035	0.06	0.28	30	-10000	0	30
LRP1	0.022	0.023	-10000	0	-0.35	2	2
cell migration	0.052	0.065	0.24	10	-0.18	18	28
FN1	0.019	0.036	-10000	0	-0.35	5	5
alphaM/beta2 Integrin/Thy1	0.044	0.038	0.24	6	-0.2	3	9
MPO	0.025	0.03	0.28	7	-10000	0	7
KNG1	0.031	0.058	0.29	25	-10000	0	25
RAP1/GDP	0.031	0.004	-10000	0	-10000	0	0
ROCK1	-0.02	0.13	0.27	7	-0.41	28	35
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.006	0.11	0.28	9	-0.35	45	54
CTGF	0.014	0.057	-10000	0	-0.35	13	13
alphaM/beta2 Integrin/Hck	0.045	0.044	0.26	10	-0.21	2	12
ITGAM	0.021	0.035	0.28	2	-0.35	3	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.021	0.11	0.37	3	-0.19	157	160
HP	0.049	0.15	0.28	112	-0.35	36	148
leukocyte adhesion	-0.063	0.14	0.35	1	-0.3	86	87
SELP	-0.096	0.17	-10000	0	-0.35	166	166

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.005	0.07	0.18	1	-0.21	51	52
EFNA5	0.012	0.066	0.28	2	-0.35	16	18
FYN	-0.027	0.054	0.18	4	-0.19	48	52
neuron projection morphogenesis	0.005	0.07	0.18	1	-0.21	51	52
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.005	0.07	0.19	1	-0.21	51	52
EPHA5	-0.006	0.092	-10000	0	-0.35	36	36

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.024	0.043	0.19	4	-0.2	16	20
cell-cell adhesion	0.048	0.061	0.17	95	-10000	0	95
Ephrin B/EPHB2/RasGAP	0.032	0.081	-10000	0	-0.18	60	60
ITSN1	0.023	0.003	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
SHC1	0.019	0.009	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.03	0.04	0.19	15	-0.23	6	21
Ephrin B1/EPHB1	0.008	0.069	0.19	1	-0.2	51	52
HRAS/GDP	-0.028	0.098	-10000	0	-0.23	61	61
Ephrin B/EPHB1/GRB7	0.016	0.11	0.23	17	-0.2	95	112
Endophilin/SYNJ1	-0.026	0.057	0.17	12	-0.32	1	13
KRAS	0.023	0.014	0.33	1	-10000	0	1
Ephrin B/EPHB1/Src	0.01	0.1	-10000	0	-0.19	97	97
endothelial cell migration	0.037	0.033	-10000	0	-0.18	8	8
GRB2	0.022	0.006	-10000	0	-10000	0	0
GRB7	0.038	0.074	0.32	31	-0.35	2	33
PAK1	-0.025	0.074	0.31	5	-0.33	3	8
HRAS	0.022	0.005	-10000	0	-10000	0	0
RRAS	-0.026	0.057	0.17	11	-0.18	52	63
DNM1	0.018	0.039	-10000	0	-0.35	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.038	0.079	0.18	19	-0.18	95	114
lamellipodium assembly	-0.048	0.061	-10000	0	-0.17	95	95
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.014	0.081	-10000	0	-0.21	49	49
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
EPHB2	0.024	0.019	0.28	3	-10000	0	3
EPHB3	0.024	0.06	0.28	16	-0.35	6	22
EPHB1	-0.012	0.11	0.28	1	-0.35	50	51
EPHB4	0.022	0.004	-10000	0	-10000	0	0
mol:GDP	-0.04	0.084	0.23	3	-0.24	53	56
Ephrin B/EPHB2	0.025	0.073	0.19	3	-0.18	55	58
Ephrin B/EPHB3	0.024	0.075	0.2	7	-0.19	51	58
JNK cascade	-0.022	0.081	0.29	20	-0.18	50	70
Ephrin B/EPHB1	0.004	0.094	-10000	0	-0.19	97	97
RAP1/GDP	-0.028	0.099	0.24	6	-0.28	23	29
EFNB2	0.02	0.028	-10000	0	-0.35	3	3
EFNB3	-0.015	0.11	-10000	0	-0.35	52	52
EFNB1	0.022	0.016	-10000	0	-0.35	1	1
Ephrin B2/EPHB1-2	0.019	0.07	0.19	3	-0.19	53	56
RAP1B	0.023	0.002	-10000	0	-10000	0	0
RAP1A	0.023	0.002	-10000	0	-10000	0	0
CDC42/GTP	-0.008	0.097	-10000	0	-0.23	55	55
Rap1/GTP	-0.051	0.063	-10000	0	-0.3	8	8
axon guidance	0.024	0.043	0.18	4	-0.2	16	20
MAPK3	-0.021	0.073	0.18	6	-0.28	11	17
MAPK1	-0.02	0.069	0.17	2	-0.3	8	10
Rac1/GDP	-0.038	0.093	0.36	1	-0.26	32	33
actin cytoskeleton reorganization	-0.054	0.06	-10000	0	-0.19	53	53
CDC42/GDP	-0.035	0.096	0.24	6	-0.26	32	38
PI3K	0.041	0.035	-10000	0	-0.18	8	8
EFNA5	0.012	0.066	0.28	2	-0.35	16	18
Ephrin B2/EPHB4	0.027	0.019	-10000	0	-0.2	3	3
Ephrin B/EPHB2/Intersectin/N-WASP	-0.007	0.073	-10000	0	-0.19	70	70
CDC42	0.022	0.005	-10000	0	-10000	0	0
RAS family/GTP	-0.051	0.062	-10000	0	-0.18	97	97
PTK2	0.044	0.16	0.55	48	-10000	0	48
MAP4K4	-0.022	0.081	0.29	20	-0.18	50	70
SRC	0.022	0.005	-10000	0	-10000	0	0
KALRN	0.019	0.036	-10000	0	-0.35	5	5
Intersectin/N-WASP	0.032	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.035	0.098	0.3	21	-0.29	10	31
MAP2K1	-0.017	0.074	-10000	0	-0.2	47	47
WASL	0.022	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.033	0.077	-10000	0	-0.19	52	52
cell migration	-0.018	0.11	0.24	13	-0.23	73	86
NRAS	0.023	0.001	-10000	0	-10000	0	0
SYNJ1	-0.026	0.058	0.17	12	-0.32	1	13
PXN	0.023	0.003	-10000	0	-10000	0	0
TF	-0.031	0.061	0.17	10	-0.31	2	12
HRAS/GTP	-0.003	0.087	-10000	0	-0.18	98	98
Ephrin B1/EPHB1-2	0.021	0.069	0.19	4	-0.19	51	55
cell adhesion mediated by integrin	0.015	0.065	0.18	48	-0.2	9	57
RAC1	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	-0.001	0.091	-10000	0	-0.18	98	98
RAC1-CDC42/GTP	-0.048	0.065	-10000	0	-0.18	86	86
RASA1	0.019	0.036	-10000	0	-0.35	5	5
RAC1-CDC42/GDP	-0.03	0.095	0.35	1	-0.26	31	32
ruffle organization	-0.037	0.091	0.34	11	-0.3	8	19
NCK1	0.021	0.023	-10000	0	-0.35	2	2
receptor internalization	-0.03	0.06	0.16	11	-0.27	7	18
Ephrin B/EPHB2/KALRN	0.032	0.082	-10000	0	-0.19	58	58
ROCK1	0.003	0.058	0.18	44	-0.21	6	50
RAS family/GDP	-0.055	0.062	-10000	0	-0.2	54	54
Rac1/GTP	-0.049	0.065	-10000	0	-0.18	95	95
Ephrin B/EPHB1/Src/Paxillin	-0.024	0.092	-10000	0	-0.21	100	100

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.027	0.068	-10000	0	-0.22	31	31
NF kappa B1 p50/RelA/I kappa B alpha	0.005	0.089	0.34	3	-0.27	7	10
AP1	-0.033	0.12	-10000	0	-0.19	181	181
mol:PIP3	-0.024	0.062	-10000	0	-0.26	15	15
AKT1	-0.01	0.07	0.26	7	-0.29	9	16
PTK2B	-0.024	0.096	0.19	1	-0.28	44	45
RHOA	0	0.057	0.22	3	-0.29	12	15
PIK3CB	0.022	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.01	0.062	0.22	8	-0.26	5	13
MAGI3	0.023	0.002	-10000	0	-10000	0	0
RELA	0.022	0.004	-10000	0	-10000	0	0
apoptosis	-0.007	0.071	-10000	0	-0.21	51	51
HRAS/GDP	0.016	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.028	0.092	0.21	8	-0.28	37	45
NF kappa B1 p50/RelA	0.009	0.091	0.22	2	-0.24	35	37
endothelial cell migration	-0.009	0.093	-10000	0	-0.39	28	28
ADCY4	-0.053	0.12	-10000	0	-0.34	56	56
ADCY5	-0.08	0.14	-10000	0	-0.35	77	77
ADCY6	-0.046	0.11	-10000	0	-0.32	48	48
ADCY7	-0.044	0.11	-10000	0	-0.34	42	42
ADCY1	-0.051	0.12	-10000	0	-0.34	53	53
ADCY2	-0.13	0.16	-10000	0	-0.39	120	120
ADCY3	-0.047	0.11	-10000	0	-0.32	52	52
ADCY8	-0.043	0.11	-10000	0	-0.32	43	43
ADCY9	-0.072	0.14	-10000	0	-0.35	84	84
GSK3B	-0.024	0.095	0.23	8	-0.27	42	50
arachidonic acid secretion	-0.063	0.13	-10000	0	-0.35	58	58
GNG2	0.017	0.049	0.28	1	-0.35	9	10
TRIP6	0.011	0.035	-10000	0	-0.33	5	5
GNAO1	-0.047	0.11	-10000	0	-0.23	131	131
HRAS	0.022	0.005	-10000	0	-10000	0	0
NFKBIA	-0.017	0.087	0.26	6	-0.25	28	34
GAB1	0.02	0.032	-10000	0	-0.35	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.002	0.18	-10000	0	-0.82	24	24
JUN	0.018	0.042	-10000	0	-0.35	7	7
LPA/LPA2/NHERF2	0.027	0.023	0.19	2	-10000	0	2
TIAM1	-0.014	0.21	-10000	0	-0.96	24	24
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
mol:IP3	-0.009	0.061	0.22	8	-0.19	22	30
PLCB3	0.013	0.036	0.18	18	-10000	0	18
FOS	-0.088	0.17	-10000	0	-0.35	160	160
positive regulation of mitosis	-0.063	0.13	-10000	0	-0.35	58	58
LPA/LPA1-2-3	0.027	0.084	0.2	19	-0.2	49	68
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.021	0.007	-10000	0	-10000	0	0
stress fiber formation	-0.01	0.081	0.21	1	-0.3	18	19
GNAZ	-0.007	0.067	-10000	0	-0.23	40	40
EGFR/PI3K-beta/Gab1	0	0.072	-10000	0	-0.27	15	15
positive regulation of dendritic cell cytokine production	0.026	0.083	0.19	15	-0.2	49	64
LPA/LPA2/MAGI-3	0.028	0.024	0.19	2	-10000	0	2
ARHGEF1	-0.006	0.056	0.18	20	-0.2	23	43
GNAI2	0	0.055	-10000	0	-0.23	27	27
GNAI3	-0.001	0.056	-10000	0	-0.23	28	28
GNAI1	-0.003	0.06	-10000	0	-0.23	33	33
LPA/LPA3	0.01	0.07	0.19	24	-0.19	39	63
LPA/LPA2	0.015	0.023	0.19	2	-0.095	13	15
LPA/LPA1	0.004	0.067	-10000	0	-0.26	30	30
HB-EGF/EGFR	0.046	0.055	0.22	5	-0.2	12	17
HBEGF	0.042	0.066	0.12	217	-10000	0	217
mol:DAG	-0.009	0.061	0.22	8	-0.19	22	30
cAMP biosynthetic process	-0.083	0.13	0.23	1	-0.3	100	101
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
SRC	0.022	0.005	-10000	0	-10000	0	0
GNB1	0.022	0.004	-10000	0	-10000	0	0
LYN	-0.008	0.089	0.27	10	-0.24	25	35
GNAQ	0.001	0.051	-10000	0	-0.2	27	27
LPAR2	0.024	0.021	0.3	3	-10000	0	3
LPAR3	0.017	0.099	0.28	25	-0.35	26	51
LPAR1	0.009	0.068	-10000	0	-0.26	26	26
IL8	0.033	0.14	0.34	8	-0.36	20	28
PTK2	-0.015	0.062	0.18	9	-0.19	36	45
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
CASP3	-0.007	0.071	-10000	0	-0.21	51	51
EGFR	0.015	0.059	0.33	1	-0.35	13	14
PLCG1	-0.007	0.062	0.16	7	-0.21	32	39
PLD2	-0.017	0.064	0.18	8	-0.19	49	57
G12/G13	0.029	0.059	-10000	0	-0.21	25	25
PI3K-beta	0.001	0.064	-10000	0	-0.28	14	14
cell migration	0.001	0.064	-10000	0	-0.26	22	22
SLC9A3R2	0.022	0.005	-10000	0	-10000	0	0
PXN	-0.01	0.082	0.21	1	-0.3	18	19
HRAS/GTP	-0.064	0.13	-10000	0	-0.36	58	58
RAC1	0.022	0.005	-10000	0	-10000	0	0
MMP9	0.13	0.13	0.28	220	-10000	0	220
PRKCE	0.023	0.003	-10000	0	-10000	0	0
PRKCD	-0.015	0.068	0.21	12	-0.25	7	19
Gi(beta/gamma)	-0.046	0.11	-10000	0	-0.33	47	47
mol:LPA	-0.003	0.026	-10000	0	-0.14	16	16
TRIP6/p130 Cas/FAK1/Paxillin	0.006	0.081	-10000	0	-0.34	11	11
MAPKKK cascade	-0.063	0.13	-10000	0	-0.35	58	58
contractile ring contraction involved in cytokinesis	-0.002	0.061	0.22	3	-0.28	15	18
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.015	0.078	-10000	0	-0.22	66	66
GNA15	0.003	0.051	0.12	3	-0.2	26	29
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
MAPT	-0.028	0.094	0.22	8	-0.28	38	46
GNA11	-0.003	0.057	-10000	0	-0.2	36	36
Rac1/GTP	0.001	0.19	-10000	0	-0.87	24	24
MMP2	-0.009	0.094	-10000	0	-0.39	28	28

×

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

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
MET/RANBP9	0.031	0.031	0.21	3	-0.25	5	8
CRKL	-0.032	0.13	0.31	3	-0.54	22	25
mol:PIP3	-0.01	0.12	-10000	0	-0.78	12	12
AKT1	-0.01	0.11	0.35	2	-0.69	12	14
PTK2B	0.02	0.008	-10000	0	-10000	0	0
RAPGEF1	-0.033	0.13	0.29	4	-0.51	22	26
RANBP10	0.021	0.007	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
HGF/MET/SHIP2	-0.005	0.1	0.2	4	-0.21	106	110
MAP3K5	-0.025	0.13	0.29	5	-0.49	24	29
HGF/MET/CIN85/CBL/ENDOPHILINS	0.006	0.1	0.21	4	-0.19	105	109
AP1	-0.049	0.12	0.17	2	-0.22	149	151
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.019	0.009	-10000	0	-10000	0	0
apoptosis	-0.21	0.35	-10000	0	-0.71	172	172
STAT3 (dimer)	-0.027	0.092	-10000	0	-0.33	17	17
GAB1/CRKL/SHP2/PI3K	-0.008	0.13	-10000	0	-0.47	22	22
INPP5D	0.022	0.016	-10000	0	-0.35	1	1
CBL/CRK	-0.022	0.13	0.3	3	-0.52	22	25
PTPN11	0.023	0.003	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.022	0.005	-10000	0	-10000	0	0
PTEN	0.021	0.006	-10000	0	-10000	0	0
ELK1	0.011	0.1	0.3	47	-10000	0	47
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.02	0.074	-10000	0	-0.26	26	26
PAK1	-0.009	0.11	0.36	6	-0.66	12	18
HGF/MET/RANBP10	-0.007	0.1	0.2	4	-0.21	106	110
HRAS	-0.039	0.14	-10000	0	-0.54	24	24
DOCK1	-0.032	0.14	0.32	8	-0.49	25	33
GAB1	-0.032	0.14	-10000	0	-0.58	22	22
CRK	-0.031	0.13	0.33	2	-0.56	21	23
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.069	0.19	-10000	0	-0.42	110	110
JUN	0.018	0.042	-10000	0	-0.35	7	7
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.026	0.073	-10000	0	-0.17	104	104
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
cell morphogenesis	-0.023	0.13	0.3	15	-0.4	22	37
GRB2/SHC	-0.002	0.071	-10000	0	-0.22	18	18
FOS	-0.089	0.17	-10000	0	-0.35	160	160
GLMN	0.003	0.001	-10000	0	-10000	0	0
cell motility	0.011	0.1	0.3	47	-10000	0	47
HGF/MET/MUC20	-0.016	0.098	0.19	4	-0.21	106	110
cell migration	-0.002	0.07	-10000	0	-0.21	18	18
GRB2	0.022	0.006	-10000	0	-10000	0	0
CBL	0.022	0.005	-10000	0	-10000	0	0
MET/RANBP10	0.028	0.033	0.21	4	-0.25	5	9
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.02	0.088	0.17	1	-0.21	89	90
MET/MUC20	0.015	0.029	0.19	4	-0.24	5	9
RAP1B	-0.034	0.12	0.27	4	-0.49	21	25
RAP1A	-0.035	0.12	0.27	4	-0.48	22	26
HGF/MET/RANBP9	-0.004	0.1	0.2	3	-0.21	102	105
RAF1	-0.036	0.14	-10000	0	-0.5	25	25
STAT3	-0.026	0.092	-10000	0	-0.33	16	16
cell proliferation	-0.017	0.14	0.29	14	-0.31	73	87
RPS6KB1	-0.009	0.054	-10000	0	-0.28	13	13
MAPK3	0.006	0.14	0.62	21	-10000	0	21
MAPK1	0.019	0.16	0.62	32	-10000	0	32
RANBP9	0.023	0.004	-10000	0	-10000	0	0
MAPK8	-0.019	0.13	0.3	3	-0.46	27	30
SRC	-0.028	0.08	0.15	1	-0.2	85	86
PI3K	-0.004	0.078	-10000	0	-0.24	19	19
MET/Glomulin	0.015	0.032	0.21	4	-0.21	5	9
SOS1	0.023	0.003	-10000	0	-10000	0	0
MAP2K1	-0.034	0.13	-10000	0	-0.47	25	25
MET	0.021	0.042	0.28	4	-0.35	5	9
MAP4K1	-0.026	0.14	0.3	4	-0.52	24	28
PTK2	0.021	0.007	-10000	0	-10000	0	0
MAP2K2	-0.035	0.13	-10000	0	-0.47	24	24
BAD	-0.009	0.11	0.4	4	-0.66	12	16
MAP2K4	-0.023	0.12	0.27	5	-0.44	23	28
SHP2/GRB2/SOS1/GAB1	-0.013	0.13	-10000	0	-0.48	22	22
INPPL1	0.023	0.003	-10000	0	-10000	0	0
PXN	0.023	0.003	-10000	0	-10000	0	0
SH3KBP1	0.023	0.003	-10000	0	-10000	0	0
HGS	-0.027	0.065	-10000	0	-0.16	98	98
PLCgamma1/PKC	0.016	0.004	-10000	0	-10000	0	0
HGF	-0.05	0.15	-10000	0	-0.35	104	104
RASA1	0.019	0.036	-10000	0	-0.35	5	5
NCK1	0.021	0.023	-10000	0	-0.35	2	2
PTPRJ	0.022	0.004	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.005	0.085	-10000	0	-0.17	101	101
PDPK1	-0.011	0.11	0.24	3	-0.73	12	15
HGF/MET/SHIP	-0.005	0.1	0.2	4	-0.21	106	110

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.022	0.004	-10000	0	-10000	0	0
VLDLR	0.021	0.023	-10000	0	-0.35	2	2
LRPAP1	0.022	0.004	-10000	0	-10000	0	0
NUDC	0.022	0.005	-10000	0	-10000	0	0
RELN/LRP8	-0.039	0.12	0.23	8	-0.21	179	187
CaM/Ca2+	0.017	0.003	-10000	0	-10000	0	0
KATNA1	0.023	0.003	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.065	0.09	0.18	12	-0.19	170	182
IQGAP1/CaM	0.032	0.008	-10000	0	-10000	0	0
DAB1	0.027	0.041	0.28	13	-10000	0	13
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
PLA2G7	0.02	0.038	0.28	1	-0.35	5	6
CALM1	0.022	0.004	-10000	0	-10000	0	0
DYNLT1	0.023	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.035	0.019	0.21	5	-10000	0	5
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.023	0.003	-10000	0	-10000	0	0
CDK5R1	0.022	0.013	0.28	1	-10000	0	1
LIS1/Poliovirus Protein 3A	-0.008	0.003	-10000	0	-10000	0	0
CDK5R2	0.048	0.079	0.28	56	-10000	0	56
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.038	0.12	0.21	16	-0.21	178	194
YWHAE	0.021	0.007	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.041	0.096	0.29	11	-0.22	5	16
MAP1B	-0.006	0.047	-10000	0	-0.23	23	23
RAC1	0.008	0.004	-10000	0	-10000	0	0
p35/CDK5	-0.064	0.08	0.18	9	-10000	0	9
RELN	-0.1	0.18	0.28	7	-0.35	182	189
PAFAH/LIS1	0.019	0.025	0.2	1	-0.21	5	6
LIS1/CLIP170	0.021	0.008	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.036	0.08	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.05	0.11	0.25	2	-0.27	16	18
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.05	0.084	0.22	10	-0.21	5	15
LIS1/IQGAP1	0.021	0.008	-10000	0	-10000	0	0
RHOA	0.008	0.004	-10000	0	-10000	0	0
PAFAH1B1	-0.01	0.004	-10000	0	-10000	0	0
PAFAH1B3	0.027	0.034	0.28	9	-10000	0	9
PAFAH1B2	0.022	0.017	-10000	0	-0.35	1	1
MAP1B/LIS1/Dynein heavy chain	0.009	0.041	-10000	0	-0.17	1	1
NDEL1/Katanin 60/Dynein heavy chain	-0.032	0.1	0.3	9	-0.22	8	17
LRP8	0.025	0.026	0.29	5	-10000	0	5
NDEL1/Katanin 60	-0.044	0.095	0.29	10	-0.22	9	19
P39/CDK5	-0.052	0.1	0.18	44	-0.18	56	100
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.02	0.008	-10000	0	-10000	0	0
CDK5	-0.064	0.084	0.18	10	-0.18	169	179
PPP2R5D	0.023	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.018	0.007	-10000	0	-10000	0	0
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.03	0.11	0.21	12	-0.18	173	185
RELN/VLDLR	-0.027	0.12	0.21	7	-0.19	176	183
CDC42	0.008	0.003	-10000	0	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.083	0.46	-10000	0	-1.1	46	46
STAT6 (cleaved dimer)	-0.11	0.44	0.59	1	-1.1	55	56
IGHG1	0.005	0.22	0.4	10	-0.7	7	17
IGHG3	-0.097	0.44	0.59	1	-1	55	56
AKT1	-0.023	0.27	0.59	1	-0.85	11	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.009	0.22	0.52	2	-0.91	7	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.026	0.28	0.53	2	-0.76	21	23
THY1	-0.094	0.46	0.67	1	-1.1	49	50
MYB	0.048	0.076	0.28	52	-10000	0	52
HMGA1	0.061	0.092	0.28	78	-10000	0	78
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.018	0.31	0.58	4	-0.69	29	33
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.009	0.27	0.51	3	-0.87	10	13
SP1	0.025	0.012	-10000	0	-10000	0	0
INPP5D	0.022	0.016	-10000	0	-0.35	1	1
SOCS5	0.004	0.037	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.098	0.45	0.6	1	-1.1	53	54
SOCS1	-0.046	0.32	0.51	2	-0.7	45	47
SOCS3	-0.015	0.27	0.55	1	-0.98	6	7
FCER2	-0.073	0.4	0.72	2	-0.94	44	46
PARP14	0.024	0.006	-10000	0	-10000	0	0
CCL17	-0.09	0.46	0.74	2	-1.1	52	54
GRB2	0.022	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	0.014	0.22	0.46	5	-0.69	8	13
T cell proliferation	-0.11	0.45	0.64	1	-1.1	50	51
IL4R/JAK1	-0.11	0.45	-10000	0	-1.1	51	51
EGR2	-0.12	0.52	0.72	1	-1.3	56	57
JAK2	0.011	0.081	-10000	0	-0.36	9	9
JAK3	0.024	0.027	0.3	4	-10000	0	4
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
JAK1	0.017	0.037	-10000	0	-0.35	1	1
COL1A2	0.001	0.23	-10000	0	-1.1	8	8
CCL26	-0.094	0.46	-10000	0	-1.1	47	47
IL4R	-0.096	0.49	0.74	2	-1.2	49	51
PTPN6	0.008	0.035	0.34	1	-10000	0	1
IL13RA2	-0.089	0.46	0.67	1	-1.1	50	51
IL13RA1	0.018	0.066	0.18	1	-10000	0	1
IRF4	0.001	0.24	0.51	2	-1	19	21
ARG1	0.017	0.18	0.44	2	-0.55	7	9
CBL	-0.022	0.28	0.51	4	-0.66	27	31
GTF3A	0.025	0.008	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
IL13RA1/JAK2	0.03	0.1	0.22	8	-0.26	7	15
IRF4/BCL6	0	0.22	-10000	0	-0.95	19	19
CD40LG	0.017	0.06	-10000	0	-0.32	15	15
MAPK14	-0.02	0.28	0.52	4	-0.7	23	27
mitosis	-0.019	0.26	0.52	2	-0.79	11	13
STAT6	-0.098	0.53	0.8	3	-1.2	54	57
SPI1	0.025	0.02	0.28	3	-10000	0	3
RPS6KB1	-0.016	0.25	0.56	1	-0.76	11	12
STAT6 (dimer)	-0.098	0.53	0.8	3	-1.2	54	57
STAT6 (dimer)/PARP14	-0.11	0.47	0.64	1	-1.2	53	54
mast cell activation	-0.002	0.018	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.014	0.27	0.57	3	-0.85	12	15
FRAP1	-0.023	0.27	0.59	1	-0.85	11	12
LTA	-0.092	0.46	0.69	2	-1.1	48	50
FES	0.022	0.017	-10000	0	-0.35	1	1
T-helper 1 cell differentiation	0.094	0.52	1.2	54	-0.8	3	57
CCL11	-0.11	0.46	-10000	0	-1.1	56	56
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.007	0.26	0.53	3	-0.9	9	12
IL2RG	0.023	0.042	0.29	6	-0.35	3	9
IL10	-0.064	0.47	0.76	10	-1.1	44	54
IRS1	-0.013	0.11	-10000	0	-0.35	51	51
IRS2	-0.024	0.12	-10000	0	-0.35	66	66
IL4	0.015	0.21	-10000	0	-0.95	9	9
IL5	-0.099	0.46	0.67	1	-1.1	52	53
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.056	0.41	0.66	4	-0.9	49	53
COL1A1	-0.017	0.29	-10000	0	-1	18	18
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.11	0.46	-10000	0	-1.2	45	45
IL2R gamma/JAK3	0.036	0.044	0.31	7	-0.25	3	10
TFF3	-0.095	0.53	0.77	1	-1.2	62	63
ALOX15	-0.077	0.47	0.72	2	-1.1	47	49
MYBL1	0.021	0.007	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.095	0.42	0.64	2	-0.95	57	59
SHC1	0.019	0.009	-10000	0	-10000	0	0
CEBPB	0.023	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.029	0.27	0.51	2	-0.82	14	16
mol:PI-3-4-5-P3	-0.022	0.27	0.59	1	-0.85	11	12
PI3K	-0.027	0.28	0.59	1	-0.93	11	12
DOK2	0.021	0.021	0.28	3	-10000	0	3
ETS1	0.001	0.04	-10000	0	-0.33	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	0.018	0.21	0.44	5	-0.59	10	15
ITGB3	-0.22	0.62	0.67	1	-1.2	119	120
PIGR	-0.097	0.57	0.78	9	-1.2	73	82
IGHE	0	0.071	0.18	27	-0.17	6	33
MAPKKK cascade	0.019	0.21	0.44	5	-0.58	10	15
BCL6	0.019	0.019	-10000	0	-0.35	1	1
OPRM1	-0.096	0.46	0.69	1	-1.1	48	49
RETNLB	-0.096	0.46	0.7	1	-1.1	48	49
SELP	-0.3	0.69	0.78	8	-1.2	185	193
AICDA	-0.098	0.44	0.66	1	-1.1	51	52

×

Visual signal transduction: Rods

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
mol:K +	0.022	0.005	-10000	0	-10000	0	0
GNAT1/GTP	0.016	0.017	0.19	5	-10000	0	5
Metarhodopsin II/Arrestin	0.026	0.014	0.19	3	-10000	0	3
PDE6G/GNAT1/GTP	0.037	0.043	0.19	38	-0.2	1	39
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.022	0.026	0.28	5	-10000	0	5
GRK1	0.018	0.013	0.28	1	-10000	0	1
CNG Channel	0.039	0.059	0.23	8	-0.17	22	30
mol:Na +	0.041	0.047	0.27	3	-0.18	7	10
mol:ADP	0.018	0.012	0.28	1	-10000	0	1
RGS9-1/Gbeta5/R9AP	-0.007	0.11	0.21	14	-0.21	111	125
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.051	0.054	0.32	3	-0.18	7	10
CNGB1	0.032	0.055	0.28	25	-10000	0	25
RDH5	0.024	0.019	0.28	3	-10000	0	3
SAG	0.019	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.064	0.31	16	-10000	0	16
Na + (4 Units)	0.031	0.039	0.2	3	-0.17	7	10
RGS9	-0.057	0.15	-10000	0	-0.35	113	113
GNB1/GNGT1	0.091	0.084	0.21	179	-10000	0	179
GNAT1/GDP	0.001	0.097	0.2	15	-0.18	111	126
GUCY2D	0.026	0.039	0.28	12	-10000	0	12
GNGT1	0.11	0.12	0.28	188	-10000	0	188
GUCY2F	0.019	0.003	-10000	0	-10000	0	0
GNB5	0.022	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	0.016	0.048	0.17	11	-0.18	22	33
mol:11-cis-retinal	0.024	0.019	0.28	3	-10000	0	3
mol:cGMP	0.038	0.04	0.25	1	-0.18	7	8
GNB1	0.022	0.004	-10000	0	-10000	0	0
Rhodopsin	0.032	0.019	0.21	5	-10000	0	5
SLC24A1	0.022	0.005	-10000	0	-10000	0	0
CNGA1	0.03	0.042	0.28	15	-10000	0	15
Metarhodopsin II	0.023	0.015	0.18	4	-10000	0	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.05	0.048	0.35	1	-0.19	7	8
RGS9BP	0.033	0.056	0.29	23	-10000	0	23
Metarhodopsin II/Transducin	0.036	0.043	0.16	27	-10000	0	27
GCAP Family/Ca ++	0.038	0.037	0.19	15	-0.19	7	22
PDE6A/B	0.023	0.057	0.21	4	-0.24	21	25
mol:Pi	-0.008	0.11	0.21	14	-0.21	111	125
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.086	0.075	0.2	166	-10000	0	166
PDE6B	0.008	0.074	0.28	2	-0.35	21	23
PDE6A	0.024	0.022	0.28	4	-10000	0	4
PDE6G	0.043	0.075	0.29	45	-0.35	1	46
RHO	0.02	0.02	0.28	3	-10000	0	3
PDE6	0.009	0.12	0.27	10	-0.19	124	134
GUCA1A	0.028	0.046	0.28	17	-10000	0	17
GC2/GCAP Family	0.05	0.04	-10000	0	-0.2	7	7
GUCA1C	0.016	0.002	-10000	0	-10000	0	0
GUCA1B	0.018	0.042	-10000	0	-0.35	7	7

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.026	0.012	-10000	0	-10000	0	0
ARNO/beta Arrestin1-2	-0.012	0.13	-10000	0	-0.78	11	11
EGFR	0.014	0.059	0.33	1	-0.35	13	14
EPHA2	0.022	0.005	-10000	0	-10000	0	0
USP6	0.021	0.006	-10000	0	-10000	0	0
IQSEC1	0.022	0.017	-10000	0	-0.35	1	1
EGFR/EGFR/EGF/EGF	0.031	0.058	0.21	21	-0.25	14	35
ARRB2	0.007	0.002	-10000	0	-10000	0	0
mol:GTP	0.011	0.05	0.13	26	-0.15	15	41
ARRB1	0.021	0.023	-10000	0	-0.35	2	2
FBXO8	0.022	0.004	-10000	0	-10000	0	0
TSHR	0.026	0.057	0.28	19	-0.35	3	22
EGF	0.03	0.056	0.28	21	-0.35	2	23
somatostatin receptor activity	0	0	0.001	6	-0.001	68	74
ARAP2	0.02	0.028	-10000	0	-0.35	3	3
mol:GDP	-0.063	0.12	0.18	5	-0.3	76	81
mol:PI-3-4-5-P3	0	0	0.001	3	-0.001	31	34
ITGA2B	0.018	0.041	0.28	1	-0.35	6	7
ARF6	0.023	0.003	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.043	0.031	0.21	1	-0.19	2	3
ADAP1	0.022	0.005	-10000	0	-10000	0	0
KIF13B	0.02	0.008	-10000	0	-10000	0	0
HGF/MET	-0.022	0.12	0.21	4	-0.25	106	110
PXN	0.023	0.003	-10000	0	-10000	0	0
ARF6/GTP	-0.059	0.11	0.22	6	-0.27	69	75
EGFR/EGFR/EGF/EGF/ARFGEP100	0.041	0.054	0.2	20	-0.21	15	35
ADRB2	-0.043	0.14	-10000	0	-0.35	93	93
receptor agonist activity	0	0	0	3	0	58	61
actin filament binding	0	0	0	5	-0.001	69	74
SRC	0.022	0.005	-10000	0	-10000	0	0
ITGB3	-0.04	0.14	0.28	2	-0.35	90	92
GNAQ	0.021	0.017	-10000	0	-0.35	1	1
EFA6/PI-4-5-P2	0	0	0.001	10	-0.001	39	49
ARF6/GDP	-0.016	0.14	0.25	11	-0.42	44	55
ARF6/GDP/GULP/ACAP1	-0.058	0.14	-10000	0	-0.34	68	68
alphaIIb/beta3 Integrin/paxillin/GIT1	0.013	0.094	0.21	3	-0.19	92	95
ACAP1	0.022	0.026	0.28	3	-0.35	1	4
ACAP2	0.02	0.017	-10000	0	-0.35	1	1
LHCGR/beta Arrestin2	0.011	0.018	-10000	0	-10000	0	0
EFNA1	0.02	0.02	0.3	2	-10000	0	2
HGF	-0.05	0.15	-10000	0	-0.35	104	104
CYTH3	-0.006	0.001	-10000	0	-10000	0	0
CYTH2	-0.005	0.14	-10000	0	-0.99	11	11
NCK1	0.021	0.023	-10000	0	-0.35	2	2
fibronectin binding	0	0	0.001	7	0	54	61
endosomal lumen acidification	0	0	0.001	11	0	55	66
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.018	0.12	-10000	0	-0.35	59	59
GNAQ/ARNO	0.007	0.13	-10000	0	-0.92	11	11
mol:Phosphatidic acid	0	0	0	1	-10000	0	1
PIP3-E	0	0	0	6	0	8	14
MET	0.021	0.042	0.28	4	-0.35	5	9
GNA14	-0.01	0.1	-10000	0	-0.35	45	45
GNA15	0.025	0.03	0.28	7	-10000	0	7
GIT1	0.022	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	9	-0.001	49	58
GNA11	0.014	0.051	-10000	0	-0.35	10	10
LHCGR	0.004	0.017	-10000	0	-10000	0	0
AGTR1	-0.061	0.15	0.28	2	-0.35	113	115
desensitization of G-protein coupled receptor protein signaling pathway	0.011	0.018	-10000	0	-10000	0	0
IPCEF1/ARNO	0.019	0.13	-10000	0	-0.83	11	11
alphaIIb/beta3 Integrin	-0.017	0.11	0.21	3	-0.24	96	99

×

EGFR-dependent Endothelin signaling events

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
HRAS	0.022	0.005	-10000	0	-10000	0	0
EGFR	0.014	0.059	0.33	1	-0.35	13	14
EGF/EGFR	-0.019	0.1	0.18	1	-0.18	151	152
EGF/EGFR dimer/SHC/GRB2/SOS1	0.048	0.052	0.23	1	-0.18	10	11
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.082	0.17	-10000	0	-0.35	150	150
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.031	0.055	0.28	21	-0.35	2	23
EGF/EGFR dimer/SHC	0.037	0.049	0.2	18	-0.21	10	28
mol:GDP	0.043	0.049	0.21	1	-0.18	10	11
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.018	0.042	-10000	0	-0.35	7	7
GRB2/SOS1	0.032	0.009	-10000	0	-10000	0	0
HRAS/GTP	0.028	0.037	-10000	0	-0.17	10	10
SHC1	0.019	0.009	-10000	0	-10000	0	0
HRAS/GDP	0.04	0.046	-10000	0	-0.17	10	10
FRAP1	-0.013	0.029	0.17	5	-0.17	10	15
EGF/EGFR dimer	0.032	0.058	0.21	21	-0.24	14	35
SOS1	0.023	0.003	-10000	0	-10000	0	0
GRB2	0.022	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.048	0.13	-10000	0	-0.25	152	152

×

HIF-2-alpha transcription factor 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
MMP14	-0.003	0.089	-10000	0	-0.63	8	8
oxygen homeostasis	-0.008	0.013	-10000	0	-10000	0	0
TCEB2	0.023	0.012	0.28	1	-10000	0	1
TCEB1	0.021	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.002	0.092	0.24	1	-0.26	6	7
EPO	-0.084	0.17	-10000	0	-0.5	27	27
FIH (dimer)	-0.003	0.028	-10000	0	-10000	0	0
APEX1	-0.008	0.031	-10000	0	-10000	0	0
SERPINE1	-0.081	0.16	-10000	0	-0.41	52	52
FLT1	-0.043	0.19	-10000	0	-0.71	33	33
ADORA2A	-0.065	0.17	0.3	28	-0.39	51	79
germ cell development	-0.08	0.17	-10000	0	-0.42	54	54
SLC11A2	-0.08	0.16	-10000	0	-0.4	50	50
BHLHE40	-0.079	0.16	-10000	0	-0.4	51	51
HIF1AN	-0.003	0.028	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.037	0.11	-10000	0	-0.31	14	14
ETS1	0.021	0.033	-10000	0	-0.36	1	1
CITED2	-0.031	0.19	-10000	0	-0.88	24	24
KDR	-0.072	0.28	-10000	0	-0.88	52	52
PGK1	-0.08	0.16	-10000	0	-0.4	51	51
SIRT1	0.02	0.024	-10000	0	-0.35	2	2
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.076	0.19	-10000	0	-0.44	51	51
EPAS1	-0.031	0.07	-10000	0	-0.27	11	11
SP1	0.025	0.007	-10000	0	-10000	0	0
ABCG2	-0.16	0.24	-10000	0	-0.44	207	207
EFNA1	-0.076	0.16	0.35	1	-0.4	51	52
FXN	-0.065	0.17	0.3	29	-0.39	49	78
POU5F1	-0.082	0.17	-10000	0	-0.43	54	54
neuron apoptosis	0.075	0.18	0.44	51	-10000	0	51
EP300	0.021	0.006	-10000	0	-10000	0	0
EGLN3	-0.003	0.038	0.28	3	-0.37	1	4
EGLN2	-0.004	0.028	-10000	0	-10000	0	0
EGLN1	-0.002	0.025	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.04	0.021	0.2	1	-0.21	1	2
VHL	0.022	0.017	-10000	0	-0.35	1	1
ARNT	-0.005	0.027	-10000	0	-10000	0	0
SLC2A1	-0.064	0.18	0.3	30	-0.39	49	79
TWIST1	-0.084	0.21	0.3	29	-0.5	62	91
ELK1	0.022	0.022	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.033	0.11	-10000	0	-0.32	8	8
VEGFA	-0.079	0.16	-10000	0	-0.4	50	50
CREBBP	0.022	0.005	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.006	0.044	0.16	36	-0.18	2	38
RFC1	0.006	0.046	0.16	38	-0.18	3	41
PRKDC	0.02	0.071	0.2	67	-0.18	2	69
RIPK1	0.022	0.007	-10000	0	-10000	0	0
CASP7	-0.002	0.096	-10000	0	-0.55	15	15
FASLG/FAS/FADD/FAF1	0.018	0.053	0.17	40	-0.2	3	43
MAP2K4	0.018	0.093	0.28	7	-0.32	18	25
mol:ceramide	0.012	0.049	0.19	1	-0.22	4	5
GSN	0.005	0.046	0.16	36	-0.18	5	41
FASLG/FAS/FADD/FAF1/Caspase 8	0.021	0.055	0.24	4	-10000	0	4
FAS	0.018	0.033	-10000	0	-0.35	4	4
BID	-0.015	0.019	0.24	2	-0.16	1	3
MAP3K1	0.015	0.091	0.27	6	-0.38	15	21
MAP3K7	0.022	0.007	-10000	0	-10000	0	0
RB1	0.006	0.044	0.16	36	-0.18	2	38
CFLAR	0.022	0.006	-10000	0	-10000	0	0
HGF/MET	-0.034	0.13	0.2	3	-0.23	153	156
ARHGDIB	0.006	0.047	0.17	38	-0.18	3	41
FADD	0.022	0.01	-10000	0	-10000	0	0
actin filament polymerization	-0.001	0.053	0.18	16	-0.16	36	52
NFKB1	-0.003	0.11	-10000	0	-0.58	17	17
MAPK8	0.013	0.11	0.32	9	-0.44	20	29
DFFA	0.007	0.05	0.17	40	-0.18	2	42
DNA fragmentation during apoptosis	0.002	0.054	0.17	39	-0.18	15	54
FAS/FADD/MET	0.038	0.04	0.2	4	-0.21	9	13
CFLAR/RIP1	0.032	0.01	-10000	0	-10000	0	0
FAIM3	0.019	0.026	0.28	1	-0.35	2	3
FAF1	0.022	0.01	-10000	0	-10000	0	0
PARP1	0.007	0.048	0.17	40	-0.18	3	43
DFFB	0.007	0.046	0.17	39	-0.18	2	41
CHUK	-0.007	0.1	0.31	1	-0.55	16	17
FASLG	0.021	0.042	0.29	8	-0.35	2	10
FAS/FADD	0.029	0.028	-10000	0	-0.24	4	4
HGF	-0.05	0.15	-10000	0	-0.35	104	104
LMNA	0.012	0.068	0.23	27	-0.17	7	34
CASP6	0.006	0.049	0.17	38	-0.18	3	41
CASP10	0.021	0.024	-10000	0	-0.35	2	2
CASP3	0.012	0.052	0.2	37	-10000	0	37
PTPN13	-0.025	0.12	-10000	0	-0.35	68	68
CASP8	-0.016	0.022	0.3	2	-0.19	1	3
IL6	-0.012	0.22	-10000	0	-0.86	28	28
MET	0.021	0.042	0.28	4	-0.35	5	9
ICAD/CAD	0.005	0.047	0.16	40	-0.17	1	41
FASLG/FAS/FADD/FAF1/Caspase 10	0.012	0.049	0.19	1	-0.22	4	5
activation of caspase activity by cytochrome c	-0.015	0.019	0.24	2	-0.16	1	3
PAK2	0.021	0.076	0.21	69	-0.18	2	71
BCL2	-0.008	0.1	-10000	0	-0.35	44	44

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.036	0.1	0.29	29	-10000	0	29
GNAI2	0.022	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	0.03	0.029	0.19	10	-0.2	3	13
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.065	0.16	-10000	0	-0.35	124	124
RhoA/GTP	-0.036	0.1	-10000	0	-0.29	29	29
negative regulation of cAMP metabolic process	-0.039	0.1	0.17	2	-0.22	116	118
GNAZ	0.01	0.065	-10000	0	-0.35	17	17
GNAI3	0.023	0.002	-10000	0	-10000	0	0
GNA12	0.022	0.005	-10000	0	-10000	0	0
S1PR5	0.025	0.053	0.29	13	-0.35	4	17
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.038	0.1	0.17	2	-0.22	113	115
RhoA/GDP	0.016	0.004	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
GNAI1	0.017	0.045	-10000	0	-0.35	8	8

×

Glypican 2 network

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.Total.Perturbations
MDK	0.023	0.014	0.33	1	-9999	1
GPC2	0.041	0.068	0.28	39	-9999	39
GPC2/Midkine	0.043	0.045	0.21	34	-9999	34
neuron projection morphogenesis	0.043	0.045	0.21	34	-9999	34

×

Coregulation of Androgen receptor activity

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
NRIP1	0.021	0.028	-10000	0	-0.35	3	3
SVIL	-0.017	0.12	-10000	0	-0.35	57	57
ZNF318	0.02	0.011	-10000	0	-10000	0	0
JMJD2C	-0.003	0.031	0.083	9	-0.13	27	36
T-DHT/AR/Ubc9	-0.01	0.095	-10000	0	-0.21	92	92
CARM1	0.022	0.006	-10000	0	-10000	0	0
PRDX1	0.023	0.003	-10000	0	-10000	0	0
PELP1	0.021	0.006	-10000	0	-10000	0	0
CTNNB1	0.023	0.005	-10000	0	-10000	0	0
AKT1	0.021	0.009	-10000	0	-10000	0	0
PTK2B	0.02	0.008	-10000	0	-10000	0	0
MED1	0.02	0.009	-10000	0	-10000	0	0
MAK	0.038	0.067	0.28	38	-10000	0	38
response to oxidative stress	0	0.001	-10000	0	-10000	0	0
HIP1	0.02	0.032	-10000	0	-0.35	4	4
GSN	0.019	0.036	-10000	0	-0.35	5	5
NCOA2	0.009	0.065	-10000	0	-0.35	17	17
NCOA6	0.023	0.005	-10000	0	-10000	0	0
DNA-PK	0.036	0.022	-10000	0	-10000	0	0
NCOA4	0.022	0.005	-10000	0	-10000	0	0
PIAS3	0.019	0.009	-10000	0	-10000	0	0
cell proliferation	0.017	0.066	0.21	33	-0.52	2	35
XRCC5	0.021	0.008	-10000	0	-10000	0	0
UBE3A	0.023	0.006	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.028	0.11	0.19	1	-0.22	126	127
FHL2	-0.005	0.092	-10000	0	-0.76	6	6
RANBP9	0.023	0.005	-10000	0	-10000	0	0
JMJD1A	0.005	0.022	0.087	22	-0.11	8	30
CDK6	0.014	0.055	-10000	0	-0.35	12	12
TGFB1I1	-0.09	0.17	-10000	0	-0.35	163	163
T-DHT/AR/CyclinD1	-0.008	0.095	0.19	1	-0.21	90	91
XRCC6	0.02	0.009	-10000	0	-10000	0	0
T-DHT/AR	-0.007	0.11	-10000	0	-0.21	106	106
CTDSP1	0.023	0.004	-10000	0	-10000	0	0
CTDSP2	0.021	0.009	-10000	0	-10000	0	0
BRCA1	0.023	0.006	-10000	0	-10000	0	0
TCF4	0.007	0.069	-10000	0	-0.35	19	19
CDKN2A	0.12	0.13	0.28	216	-10000	0	216
SRF	0.024	0.017	-10000	0	-0.14	4	4
NKX3-1	-0.015	0.053	0.086	3	-0.12	89	92
KLK3	-0.014	0.059	-10000	0	-10000	0	0
TMF1	0.022	0.005	-10000	0	-10000	0	0
HNRNPA1	0.021	0.009	-10000	0	-10000	0	0
AOF2	0.001	0.003	-10000	0	-10000	0	0
APPL1	-0.012	0.004	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.01	0.094	-10000	0	-0.21	89	89
AR	-0.042	0.14	-10000	0	-0.35	91	91
UBA3	0.023	0.005	-10000	0	-10000	0	0
PATZ1	0.02	0.009	-10000	0	-10000	0	0
PAWR	0.023	0.002	-10000	0	-10000	0	0
PRKDC	0.019	0.01	-10000	0	-10000	0	0
PA2G4	0.02	0.009	-10000	0	-10000	0	0
UBE2I	0.022	0.005	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.007	0.085	-10000	0	-0.19	89	89
RPS6KA3	0.023	0.017	-10000	0	-0.35	1	1
T-DHT/AR/ARA70	-0.01	0.095	-10000	0	-0.21	90	90
LATS2	0.02	0.018	-10000	0	-0.35	1	1
T-DHT/AR/PRX1	-0.007	0.085	-10000	0	-0.19	90	90
Cyclin D3/CDK11 p58	0.017	0.003	-10000	0	-10000	0	0
VAV3	0.083	0.11	0.28	125	-10000	0	125
KLK2	-0.044	0.18	-10000	0	-0.74	32	32
CASP8	0.023	0.003	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.001	0.094	-10000	0	-0.2	84	84
TMPRSS2	-0.011	0.12	0.3	1	-0.73	11	12
CCND1	0.024	0.022	0.31	3	-10000	0	3
PIAS1	0.023	0.006	-10000	0	-10000	0	0
mol:T-DHT	-0.001	0.015	-10000	0	-0.051	36	36
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.023	0.008	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.013	0.098	-10000	0	-0.21	97	97
CMTM2	0.021	0.021	0.28	3	-10000	0	3
SNURF	-0.006	0.097	0.28	1	-0.35	39	40
ZMIZ1	0.017	0.036	-10000	0	-0.3	4	4
CCND3	0.023	0.004	-10000	0	-10000	0	0
TGIF1	0.02	0.01	-10000	0	-10000	0	0
FKBP4	0.023	0.005	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.047	0.069	-10000	0	-0.34	8	8
SMARCC2	0.023	0.006	-10000	0	-10000	0	0
SMARCC1	0.022	0.007	-10000	0	-10000	0	0
TBX21	0.055	0.12	0.45	4	-0.65	10	14
SUMO2	0.018	0.014	-10000	0	-10000	0	0
STAT1 (dimer)	0.027	0.016	0.28	2	-10000	0	2
FKBP4	0.022	0.004	-10000	0	-10000	0	0
FKBP5	0.018	0.042	-10000	0	-0.35	7	7
GR alpha/HSP90/FKBP51/HSP90	-0.063	0.1	0.26	2	-0.26	62	64
PRL	0.018	0.24	0.4	24	-1.1	20	44
cortisol/GR alpha (dimer)/TIF2	-0.12	0.16	0.46	4	-0.39	43	47
RELA	0.014	0.078	-10000	0	-0.19	44	44
FGG	-0.12	0.15	0.42	4	-0.37	46	50
GR beta/TIF2	-0.081	0.11	0.27	2	-0.31	70	72
IFNG	0.089	0.15	0.41	11	-0.46	4	15
apoptosis	-0.12	0.2	0.51	6	-0.52	63	69
CREB1	0.03	0.023	-10000	0	-10000	0	0
histone acetylation	0.035	0.071	0.22	1	-0.25	4	5
BGLAP	0.086	0.096	0.35	6	-10000	0	6
GR/PKAc	-0.054	0.097	0.27	1	-0.24	59	60
NF kappa B1 p50/RelA	0.028	0.14	-10000	0	-0.31	66	66
SMARCD1	0.023	0.005	-10000	0	-10000	0	0
MDM2	-0.024	0.047	0.18	4	-10000	0	4
GATA3	0.027	0.057	0.28	13	-0.35	6	19
AKT1	0.02	0.004	-10000	0	-10000	0	0
CSF2	0.023	0.055	-10000	0	-10000	0	0
GSK3B	0.019	0.014	-10000	0	-10000	0	0
NR1I3	-0.078	0.19	0.5	7	-0.53	28	35
CSN2	-0.12	0.13	0.32	4	-0.33	50	54
BRG1/BAF155/BAF170/BAF60A	0.054	0.025	-10000	0	-10000	0	0
NFATC1	0.014	0.057	-10000	0	-0.35	13	13
POU2F1	0.012	0.052	-10000	0	-0.26	17	17
CDKN1A	0.014	0.071	-10000	0	-1	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.006	-10000	0	-10000	0	0
SFN	0.21	0.12	0.28	385	-10000	0	385
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.062	0.15	0.29	23	-0.24	55	78
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.15	0.27	0.46	7	-0.75	76	83
JUN	0.096	0.11	0.3	45	-0.38	3	48
IL4	0.055	0.079	-10000	0	-10000	0	0
CDK5R1	0.021	0.015	0.28	1	-10000	0	1
PRKACA	0.022	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.11	0.1	-10000	0	-0.26	119	119
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.052	0.1	0.28	1	-0.24	61	62
cortisol/GR alpha (monomer)	-0.14	0.18	0.51	6	-0.42	52	58
NCOA2	0.009	0.065	-10000	0	-0.35	17	17
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.04	0.19	0.21	6	-0.33	158	164
AP-1/NFAT1-c-4	0.1	0.19	0.4	59	-0.5	10	69
AFP	0.072	0.091	-10000	0	-10000	0	0
SUV420H1	0.022	0.004	-10000	0	-10000	0	0
IRF1	-0.062	0.09	0.34	1	-0.35	1	2
TP53	0.028	0.038	-10000	0	-0.83	1	1
PPP5C	0.023	0.004	-10000	0	-10000	0	0
KRT17	0.094	0.2	0.41	47	-0.85	10	57
KRT14	0.098	0.12	0.44	8	-10000	0	8
TBP	0.026	0.005	-10000	0	-10000	0	0
CREBBP	-0.009	0.048	-10000	0	-0.25	1	1
HDAC1	0.022	0.004	-10000	0	-10000	0	0
HDAC2	0.022	0.007	-10000	0	-10000	0	0
AP-1	0.1	0.19	0.4	59	-0.5	10	69
MAPK14	0.018	0.014	-10000	0	-10000	0	0
MAPK10	-0.058	0.15	-10000	0	-0.35	111	111
MAPK11	0.016	0.026	-10000	0	-0.35	2	2
KRT5	0.1	0.23	0.4	56	-0.93	14	70
interleukin-1 receptor activity	-0.001	0.002	-10000	0	-10000	0	0
NCOA1	0.023	0.016	-10000	0	-0.35	1	1
STAT1	0.027	0.016	0.28	2	-10000	0	2
CGA	0.074	0.088	0.46	3	-10000	0	3
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.087	0.11	0.29	1	-0.35	33	34
MAPK3	0.018	0.015	-10000	0	-10000	0	0
MAPK1	0.018	0.015	-10000	0	-10000	0	0
ICAM1	0.063	0.13	0.38	5	-0.42	5	10
NFKB1	0.011	0.083	-10000	0	-0.24	22	22
MAPK8	0.1	0.1	0.28	53	-0.3	3	56
MAPK9	0.018	0.014	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.12	0.2	0.51	6	-0.54	65	71
BAX	0.011	0.061	-10000	0	-0.46	1	1
POMC	0.058	0.21	0.58	7	-1.2	10	17
EP300	-0.009	0.047	-10000	0	-0.25	1	1
cortisol/GR alpha (dimer)/p53	-0.12	0.16	0.46	6	-0.42	22	28
proteasomal ubiquitin-dependent protein catabolic process	-0.028	0.043	0.26	3	-10000	0	3
SGK1	-0.037	0.12	-10000	0	-0.74	6	6
IL13	0.065	0.13	0.42	2	-0.61	1	3
IL6	0.043	0.19	0.35	8	-0.84	17	25
PRKACG	0.017	0.005	-10000	0	-10000	0	0
IL5	0.056	0.11	0.38	1	-0.54	2	3
IL2	0.071	0.15	0.37	5	-0.46	8	13
CDK5	0.021	0.008	-10000	0	-10000	0	0
PRKACB	0.019	0.039	-10000	0	-0.35	6	6
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
IL8	0.094	0.15	0.38	9	-0.43	2	11
CDK5R1/CDK5	0.027	0.02	0.21	1	-10000	0	1
NF kappa B1 p50/RelA/PKAc	0.049	0.12	-10000	0	-0.3	26	26
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.11	0.15	0.43	7	-0.37	28	35
SMARCA4	0.022	0.008	-10000	0	-10000	0	0
chromatin remodeling	-0.068	0.1	0.29	5	-0.34	16	21
NF kappa B1 p50/RelA/Cbp	0.012	0.13	-10000	0	-0.32	32	32
JUN (dimer)	0.095	0.11	0.3	45	-0.38	3	48
YWHAH	0.022	0.006	-10000	0	-10000	0	0
VIPR1	0.065	0.092	0.33	10	-0.57	3	13
NR3C1	-0.12	0.15	0.36	3	-0.4	70	73
NR4A1	-0.007	0.12	-10000	0	-0.4	44	44
TIF2/SUV420H1	0.021	0.05	-10000	0	-0.25	17	17
MAPKKK cascade	-0.12	0.2	0.51	6	-0.52	63	69
cortisol/GR alpha (dimer)/Src-1	-0.12	0.16	0.45	6	-0.39	30	36
PBX1	0	0.086	-10000	0	-0.33	32	32
POU1F1	0.01	0.06	0.28	2	-0.29	19	21
SELE	-0.012	0.31	0.36	6	-0.82	64	70
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.068	0.11	0.3	4	-0.34	16	20
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.11	0.15	0.43	7	-0.37	28	35
mol:cortisol	-0.066	0.09	0.28	6	-0.21	30	36
MMP1	0.11	0.16	0.39	4	-0.58	6	10

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.007	0.084	0.77	3	-0.62	1	4
VDR	0.029	0.042	0.29	13	-10000	0	13
FAM120B	0.022	0.004	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.013	0.076	0.26	2	-0.31	4	6
RXRs/LXRs/DNA/Oxysterols	0.029	0.085	0.29	2	-0.37	5	7
MED1	0.021	0.006	-10000	0	-10000	0	0
mol:9cRA	0.005	0.008	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.037	0.1	-10000	0	-0.2	144	144
RXRs/NUR77	0.016	0.1	0.25	5	-0.2	82	87
RXRs/PPAR	-0.015	0.087	0.18	5	-0.21	56	61
NCOR2	0.023	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.023	0.19	9	-10000	0	9
RARs/VDR/DNA/Vit D3	0.047	0.039	0.2	9	-0.18	8	17
RARA	0.022	0.006	-10000	0	-10000	0	0
NCOA1	0.022	0.017	-10000	0	-0.35	1	1
VDR/VDR/DNA	0.029	0.042	0.29	13	-10000	0	13
RARs/RARs/DNA/9cRA	0.036	0.031	-10000	0	-0.17	9	9
RARG	0.023	0.003	-10000	0	-10000	0	0
RPS6KB1	0.014	0.09	0.57	13	-10000	0	13
RARs/THRs/DNA/SMRT	-0.037	0.099	-10000	0	-0.2	142	142
THRA	0.015	0.048	-10000	0	-0.35	9	9
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.019	0.023	0.19	9	-10000	0	9
RXRs/PPAR/9cRA/PGJ2/DNA	0.025	0.081	0.28	5	-0.18	40	45
NR1H4	0.027	0.048	0.28	19	-10000	0	19
RXRs/LXRs/DNA	0.041	0.087	0.34	1	-0.26	2	3
NR1H2	0.027	0.009	-10000	0	-10000	0	0
NR1H3	0.028	0.015	0.28	1	-10000	0	1
RXRs/VDR/DNA/Vit D3	0.029	0.079	0.23	8	-0.17	56	64
NR4A1	-0.001	0.092	-10000	0	-0.35	35	35
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0	0.072	0.19	8	-0.17	45	53
RXRG	-0.014	0.12	0.31	9	-0.34	60	69
RXR alpha/CCPG	0.034	0.013	-10000	0	-10000	0	0
RXRA	0.026	0.011	-10000	0	-10000	0	0
RXRB	0.028	0.01	-10000	0	-10000	0	0
THRB	-0.055	0.15	-10000	0	-0.35	111	111
PPARG	0.004	0.084	0.33	1	-0.35	28	29
PPARD	0.023	0.003	-10000	0	-10000	0	0
TNF	0.029	0.11	0.4	3	-0.77	3	6
mol:Oxysterols	0.005	0.007	-10000	0	-10000	0	0
cholesterol transport	0.029	0.084	0.29	2	-0.37	5	7
PPARA	0.021	0.007	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.016	0.048	-10000	0	-0.35	9	9
RXRs/NUR77/BCL2	-0.034	0.11	0.17	2	-0.25	98	100
SREBF1	0.023	0.077	-10000	0	-0.5	1	1
RXRs/RXRs/DNA/9cRA	0.025	0.081	0.28	5	-0.18	40	45
ABCA1	0.025	0.073	-10000	0	-0.5	1	1
RARs/THRs	0.002	0.11	-10000	0	-0.19	123	123
RXRs/FXR	0.03	0.086	0.25	6	-0.18	54	60
BCL2	-0.008	0.1	-10000	0	-0.35	44	44

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.003	0.036	-10000	0	-0.2	13	13
NFATC2	-0.009	0.061	-10000	0	-0.21	44	44
NFATC3	0.007	0.019	-10000	0	-10000	0	0
CD40LG	-0.052	0.14	0.32	1	-0.36	49	50
PTGS2	-0.058	0.16	0.24	1	-0.38	75	76
JUNB	0.018	0.036	-10000	0	-0.35	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.014	0.016	-10000	0	-10000	0	0
CaM/Ca2+	0.014	0.016	-10000	0	-10000	0	0
CALM1	0.02	0.014	-10000	0	-10000	0	0
JUN	0.016	0.044	-10000	0	-0.35	7	7
mol:Ca2+	0	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.014	0.007	-10000	0	-10000	0	0
FOSL1	0.042	0.069	0.28	42	-10000	0	42
CREM	0.021	0.008	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.007	0.088	0.24	1	-0.28	16	17
FOS	-0.09	0.17	-10000	0	-0.35	160	160
IFNG	-0.039	0.14	0.26	9	-0.33	45	54
AP-1/NFAT1-c-4	-0.027	0.17	0.36	9	-0.37	50	59
FASLG	-0.043	0.13	0.26	5	-0.33	46	51
NFAT1-c-4/ICER1	-0.001	0.074	-10000	0	-0.22	24	24
IL2RA	-0.042	0.13	0.28	6	-0.34	40	46
FKBP12/FK506	0.017	0.003	-10000	0	-10000	0	0
CSF2	-0.046	0.13	0.27	4	-0.33	50	54
JunB/Fra1/NFAT1-c-4	0.018	0.09	0.22	16	-0.23	17	33
IL4	-0.049	0.13	0.32	1	-0.34	39	40
IL2	-0.009	0.16	-10000	0	-0.86	18	18
IL3	-0.003	0.1	-10000	0	-0.66	12	12
FKBP1A	0.022	0.004	-10000	0	-10000	0	0
BATF3	0.02	0.014	0.28	1	-10000	0	1
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.019	0.009	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.026	0.074	0.23	1	-0.42	8	9
Syndecan-4/Syndesmos	0.057	0.11	0.33	9	-0.74	2	11
positive regulation of JNK cascade	-0.034	0.13	0.36	2	-0.43	9	11
Syndecan-4/ADAM12	0.06	0.11	0.32	11	-0.74	2	13
CCL5	0.021	0.045	0.28	6	-0.35	5	11
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
DNM2	0.021	0.006	-10000	0	-10000	0	0
ITGA5	0.023	0.003	-10000	0	-10000	0	0
SDCBP	0.021	0.007	-10000	0	-10000	0	0
PLG	-0.008	0.11	0.27	9	-0.34	45	54
ADAM12	0.027	0.035	0.28	10	-10000	0	10
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.022	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.04	0.023	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.1	0.14	0.36	24	-0.74	2	26
Syndecan-4/CXCL12/CXCR4	-0.035	0.14	0.45	1	-0.46	9	10
Syndecan-4/Laminin alpha3	0.053	0.11	0.33	10	-0.74	2	12
MDK	0.023	0.014	0.33	1	-10000	0	1
Syndecan-4/FZD7	0.041	0.12	0.32	9	-0.74	2	11
Syndecan-4/Midkine	0.058	0.11	0.33	8	-0.74	2	10
FZD7	-0.036	0.14	-10000	0	-0.35	85	85
Syndecan-4/FGFR1/FGF	-0.029	0.13	-10000	0	-0.55	4	4
THBS1	-0.023	0.12	-10000	0	-0.35	65	65
integrin-mediated signaling pathway	0.052	0.11	0.31	9	-0.7	2	11
positive regulation of MAPKKK cascade	-0.034	0.13	0.36	2	-0.43	9	11
Syndecan-4/TACI	0.058	0.11	0.36	8	-0.74	2	10
CXCR4	0.023	0.002	-10000	0	-10000	0	0
cell adhesion	0.008	0.046	0.18	12	-0.23	5	17
Syndecan-4/Dynamin	0.054	0.1	0.33	9	-0.74	2	11
Syndecan-4/TSP1	0.042	0.12	0.33	7	-0.53	5	12
Syndecan-4/GIPC	0.053	0.1	0.33	8	-0.74	2	10
Syndecan-4/RANTES	0.057	0.11	0.32	10	-0.74	2	12
ITGB1	0.022	0.004	-10000	0	-10000	0	0
LAMA1	0.1	0.13	0.28	174	-0.35	4	178
LAMA3	0.013	0.057	-10000	0	-0.35	13	13
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCA	-0.013	0.14	0.72	14	-0.32	29	43
Syndecan-4/alpha-Actinin	0.057	0.11	0.33	10	-0.74	2	12
TFPI	-0.021	0.12	-10000	0	-0.35	63	63
F2	0.05	0.077	0.29	48	-10000	0	48
alpha5/beta1 Integrin	0.033	0.007	-10000	0	-10000	0	0
positive regulation of cell adhesion	0.065	0.12	0.33	16	-0.71	2	18
ACTN1	0.022	0.005	-10000	0	-10000	0	0
TNC	0.014	0.056	0.28	1	-0.35	12	13
Syndecan-4/CXCL12	-0.018	0.13	0.38	2	-0.47	9	11
FGF6	0.016	0.003	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
CXCL12	-0.2	0.18	-10000	0	-0.35	327	327
TNFRSF13B	0.027	0.045	0.28	16	-10000	0	16
FGF2	-0.17	0.19	-10000	0	-0.35	276	276
FGFR1	0.02	0.018	-10000	0	-0.35	1	1
Syndecan-4/PI-4-5-P2	0.039	0.1	0.29	6	-0.74	2	8
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.015	0.04	-10000	0	-0.3	6	6
cell migration	-0.022	0.016	-10000	0	-10000	0	0
PRKCD	0.019	0.019	-10000	0	-0.12	1	1
vasculogenesis	0.042	0.11	0.33	7	-0.51	5	12
SDC4	0.048	0.095	0.31	6	-0.88	1	7
Syndecan-4/Tenascin C	0.053	0.11	0.33	4	-0.74	2	6
Syndecan-4/PI-4-5-P2/PKC alpha	-0.033	0.018	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.055	0.1	0.33	9	-0.74	2	11
MMP9	0.13	0.13	0.28	220	-10000	0	220
Rac1/GTP	0.008	0.047	0.19	12	-0.23	5	17
cytoskeleton organization	0.056	0.1	0.33	9	-0.7	2	11
GIPC1	0.022	0.006	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.043	0.12	0.32	8	-0.55	4	12

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.017	0.084	0.3	12	-0.3	9	21
TBX21	-0.02	0.25	0.64	7	-1	17	24
B2M	0.022	0.01	-10000	0	-10000	0	0
TYK2	0.012	0.031	0.18	1	-10000	0	1
IL12RB1	0.017	0.069	0.35	13	-0.38	4	17
GADD45B	-0.009	0.2	0.58	6	-0.72	17	23
IL12RB2	0.028	0.07	0.28	32	-10000	0	32
GADD45G	-0.022	0.26	0.56	7	-0.9	28	35
natural killer cell activation	0.001	0.02	0.077	13	-0.047	15	28
RELB	0.022	0.005	-10000	0	-10000	0	0
RELA	0.022	0.004	-10000	0	-10000	0	0
IL18	0.027	0.036	0.28	9	-10000	0	9
IL2RA	0.031	0.052	0.28	20	-0.35	1	21
IFNG	0.05	0.081	0.28	60	-10000	0	60
STAT3 (dimer)	-0.015	0.2	0.53	7	-0.64	24	31
HLA-DRB5	-0.006	0.01	-10000	0	-0.023	149	149
FASLG	0.011	0.24	0.71	7	-0.86	16	23
NF kappa B2 p52/RelB	-0.012	0.2	0.45	1	-0.79	17	18
CD4	0.007	0.027	0.23	1	-10000	0	1
SOCS1	0.021	0.017	-10000	0	-0.35	1	1
EntrezGene:6955	-0.007	0.013	0.017	1	-0.027	158	159
CD3D	0.008	0.065	0.26	14	-0.35	7	21
CD3E	0.003	0.06	0.28	5	-0.36	9	14
CD3G	0.007	0.047	0.28	7	-0.36	2	9
IL12Rbeta2/JAK2	0.027	0.073	0.22	30	-0.25	9	39
CCL3	-0.009	0.22	0.72	6	-0.98	10	16
CCL4	-0.014	0.23	0.68	7	-1	13	20
HLA-A	0	0.005	-10000	0	-0.044	7	7
IL18/IL18R	0.056	0.058	0.28	9	-0.22	8	17
NOS2	-0.015	0.24	0.66	6	-0.95	19	25
IL12/IL12R/TYK2/JAK2/SPHK2	0.018	0.082	0.29	13	-0.27	9	22
IL1R1	-0.024	0.25	0.64	6	-1	18	24
IL4	-0.001	0.033	-10000	0	-0.17	2	2
JAK2	0.006	0.058	0.18	1	-0.36	9	10
EntrezGene:6957	-0.006	0.012	-10000	0	-0.023	154	154
TCR/CD3/MHC I/CD8	-0.017	0.12	0.29	3	-0.55	20	23
RAB7A	-0.001	0.2	0.58	4	-0.67	16	20
lysosomal transport	0.001	0.19	0.52	7	-0.63	17	24
FOS	-0.3	0.54	0.54	4	-1.1	172	176
STAT4 (dimer)	0.016	0.2	0.55	7	-0.61	22	29
STAT5A (dimer)	0.008	0.23	0.6	10	-0.76	19	29
GZMA	-0.024	0.26	0.66	6	-1.1	19	25
GZMB	-0.008	0.23	0.64	8	-1.1	11	19
HLX	0.02	0.008	-10000	0	-10000	0	0
LCK	-0.014	0.23	0.62	7	-0.85	18	25
TCR/CD3/MHC II/CD4	-0.042	0.12	0.18	5	-0.22	135	140
IL2/IL2R	0.061	0.057	0.27	25	-0.19	3	28
MAPK14	-0.01	0.23	0.56	7	-0.7	29	36
CCR5	-0.002	0.21	0.59	7	-0.83	16	23
IL1B	0.01	0.046	0.18	1	-0.38	4	5
STAT6	0.015	0.084	0.35	9	-0.29	5	14
STAT4	0.022	0.016	-10000	0	-0.35	1	1
STAT3	0.022	0.006	-10000	0	-10000	0	0
STAT1	0.024	0.016	0.28	2	-10000	0	2
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
NFKB2	0.022	0.005	-10000	0	-10000	0	0
IL12B	0.011	0.035	0.22	3	-10000	0	3
CD8A	0.019	0.052	0.29	4	-0.35	8	12
CD8B	0.03	0.07	0.28	25	-0.35	7	32
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.017	0.084	0.3	9	-0.3	12	21
IL2RB	0.021	0.017	-10000	0	-0.35	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.19	0.53	8	-0.57	22	30
IL2RG	0.024	0.039	0.28	6	-0.35	3	9
IL12	0.022	0.059	0.22	15	-0.26	4	19
STAT5A	0.021	0.017	-10000	0	-0.35	1	1
CD247	0.004	0.035	0.28	1	-0.36	2	3
IL2	0.027	0.046	0.28	17	-10000	0	17
SPHK2	0.023	0.004	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.015	0.06	0.28	12	-0.37	4	16
IL12/IL12R/TYK2/JAK2	-0.014	0.25	0.64	9	-0.92	18	27
MAP2K3	-0.02	0.23	0.56	7	-0.69	32	39
RIPK2	0.021	0.007	-10000	0	-10000	0	0
MAP2K6	-0.005	0.22	0.56	7	-0.68	30	37
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.007	0.012	-10000	0	-0.026	154	154
IL18RAP	0.021	0.041	0.3	3	-0.35	4	7
IL12Rbeta1/TYK2	0.022	0.062	0.29	12	-0.29	4	16
EOMES	-0.017	0.16	-10000	0	-0.79	18	18
STAT1 (dimer)	0.018	0.2	0.59	11	-0.64	18	29
T cell proliferation	0.014	0.17	0.48	7	-0.5	22	29
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.02	0.035	-10000	0	-0.35	4	4
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.005	0.16	0.5	2	-0.56	20	22
ATF2	-0.01	0.21	0.53	7	-0.67	27	34

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.024	0.055	0.18	2	-0.18	34	36
RGS9BP	0.033	0.056	0.29	23	-10000	0	23
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.018	0.013	0.28	1	-10000	0	1
mol:Na +	0.016	0.047	0.18	3	-0.2	21	24
mol:ADP	-0.014	0.009	0.11	2	-10000	0	2
GNAT2	0.023	0.019	0.28	3	-10000	0	3
RGS9-1/Gbeta5/R9AP	-0.007	0.11	0.21	14	-0.21	111	125
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.027	0.013	0.18	3	-10000	0	3
GRK7	0.021	0.012	0.28	1	-10000	0	1
CNGB3	0.004	0.072	-10000	0	-0.35	21	21
Cone Metarhodopsin II/X-Arrestin	0.014	0.008	0.19	1	-10000	0	1
mol:Ca2+	-0.008	0.062	0.18	37	-0.19	20	57
Cone PDE6	0.005	0.1	0.22	5	-0.18	109	114
Cone Metarhodopsin II	0.023	0.012	0.18	2	-10000	0	2
Na + (4 Units)	0.025	0.046	0.19	3	-0.19	21	24
GNAT2/GDP	0.003	0.097	0.2	15	-0.18	111	126
GNB5	0.022	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.012	0.026	0.18	9	-10000	0	9
Cone Transducin	0.026	0.059	0.19	2	-0.19	34	36
SLC24A2	0.019	0.014	0.33	1	-10000	0	1
GNB3/GNGT2	0.013	0.07	-10000	0	-0.25	34	34
GNB3	-0.001	0.09	-10000	0	-0.35	33	33
GNAT2/GTP	0.017	0.013	0.19	3	-10000	0	3
CNGA3	0.022	0.023	0.28	4	-10000	0	4
ARR3	0.019	0.012	0.28	1	-10000	0	1
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.016	0.047	0.19	3	-0.2	21	24
mol:Pi	-0.008	0.11	0.21	14	-0.21	111	125
Cone CNG Channel	0.033	0.048	0.19	1	-0.18	21	22
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.019	0.014	0.33	1	-10000	0	1
RGS9	-0.057	0.15	-10000	0	-0.35	113	113
PDE6C	0.018	0.014	0.33	1	-10000	0	1
GNGT2	0.02	0.028	-10000	0	-0.35	3	3
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.017	0.004	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.015	0.036	-10000	0	-0.2	14	14
EPHB2	0.024	0.019	0.28	3	-10000	0	3
Syndecan-2/TACI	0.019	0.043	0.2	15	-0.19	11	26
LAMA1	0.1	0.13	0.28	174	-0.35	4	178
Syndecan-2/alpha2 ITGB1	0.028	0.056	-10000	0	-0.19	28	28
HRAS	0.022	0.005	-10000	0	-10000	0	0
Syndecan-2/CASK	0.001	0.029	-10000	0	-0.2	11	11
ITGA5	0.023	0.003	-10000	0	-10000	0	0
BAX	-0.01	0.028	-10000	0	-10000	0	0
EPB41	0.022	0.017	-10000	0	-0.35	1	1
positive regulation of cell-cell adhesion	0.014	0.029	-10000	0	-0.18	11	11
LAMA3	0.013	0.057	-10000	0	-0.35	13	13
EZR	0.022	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.008	0.1	-10000	0	-0.35	44	44
Syndecan-2/MMP2	0.008	0.05	-10000	0	-0.21	24	24
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.026	0.04	-10000	0	-0.25	11	11
dendrite morphogenesis	0.017	0.038	0.28	3	-0.2	11	14
Syndecan-2/GM-CSF	0.016	0.038	0.2	7	-0.2	11	18
determination of left/right symmetry	0.002	0.035	-10000	0	-0.24	11	11
Syndecan-2/PKC delta	0.015	0.032	-10000	0	-0.2	11	11
GNB2L1	0.023	0.004	-10000	0	-10000	0	0
MAPK3	0.004	0.061	0.19	45	-0.18	10	55
MAPK1	0.003	0.06	0.19	42	-0.18	11	53
Syndecan-2/RACK1	0.025	0.031	-10000	0	-0.17	11	11
NF1	0.021	0.006	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.002	0.035	-10000	0	-0.24	11	11
ITGA2	0.014	0.053	-10000	0	-0.35	11	11
MAPK8	-0.002	0.032	-10000	0	-0.2	14	14
Syndecan-2/alpha2/beta1 Integrin	0.078	0.095	0.21	150	-0.17	23	173
Syndecan-2/Kininogen	0.022	0.05	0.21	24	-0.2	8	32
ITGB1	0.022	0.004	-10000	0	-10000	0	0
SRC	0.002	0.058	0.18	45	-0.17	11	56
Syndecan-2/CASK/Protein 4.1	0.014	0.03	-10000	0	-0.18	12	12
extracellular matrix organization	0.015	0.033	-10000	0	-0.2	12	12
actin cytoskeleton reorganization	0.015	0.036	-10000	0	-0.2	14	14
Syndecan-2/Caveolin-2/Ras	0.014	0.061	-10000	0	-0.19	41	41
Syndecan-2/Laminin alpha3	0.01	0.047	-10000	0	-0.21	22	22
Syndecan-2/RasGAP	0.032	0.039	-10000	0	-0.17	16	16
alpha5/beta1 Integrin	0.033	0.007	-10000	0	-10000	0	0
PRKCD	0.022	0.005	-10000	0	-10000	0	0
Syndecan-2 dimer	0.017	0.038	0.28	3	-0.2	11	14
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.019	0.037	-10000	0	-0.17	16	16
RHOA	0.022	0.005	-10000	0	-10000	0	0
SDCBP	0.021	0.007	-10000	0	-10000	0	0
TNFRSF13B	0.027	0.045	0.28	16	-10000	0	16
RASA1	0.019	0.036	-10000	0	-0.35	5	5
alpha2/beta1 Integrin	0.026	0.04	-10000	0	-0.25	11	11
Syndecan-2/Synbindin	0.016	0.031	-10000	0	-0.2	10	10
TGFB1	0.022	0.017	-10000	0	-0.35	1	1
CASP3	0.004	0.06	0.19	44	-0.18	11	55
FN1	0.019	0.036	-10000	0	-0.35	5	5
Syndecan-2/IL8	0.066	0.092	0.2	150	-0.2	11	161
SDC2	0.002	0.035	-10000	0	-0.24	11	11
KNG1	0.031	0.058	0.29	25	-10000	0	25
Syndecan-2/Neurofibromin	0.015	0.032	-10000	0	-0.2	11	11
TRAPPC4	0.022	0.005	-10000	0	-10000	0	0
CSF2	0.024	0.032	0.28	8	-10000	0	8
Syndecan-2/TGFB1	0.015	0.034	-10000	0	-0.2	12	12
Syndecan-2/Syntenin/PI-4-5-P2	0.014	0.029	-10000	0	-0.18	11	11
Syndecan-2/Ezrin	0.027	0.033	-10000	0	-0.18	11	11
PRKACA	0.002	0.055	0.19	36	-0.18	10	46
angiogenesis	0.066	0.092	0.2	150	-0.2	11	161
MMP2	0.007	0.071	-10000	0	-0.35	20	20
IL8	0.095	0.12	0.28	152	-10000	0	152
calcineurin-NFAT signaling pathway	0.019	0.043	0.2	15	-0.19	11	26

×

Signaling events mediated by PTP1B

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
PDGFRB	0.009	0.071	-10000	0	-0.35	20	20
Jak2/Leptin Receptor	-0.073	0.17	-10000	0	-0.37	95	95
PTP1B/AKT1	-0.003	0.085	0.26	1	-0.28	27	28
FYN	0.023	0.004	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.014	0.088	0.3	1	-0.3	30	31
EGFR	0.013	0.06	0.32	1	-0.36	13	14
EGF/EGFR	0.007	0.092	0.25	3	-0.25	33	36
CSF1	0.016	0.05	-10000	0	-0.35	10	10
AKT1	0.022	0.007	-10000	0	-10000	0	0
INSR	0.021	0.007	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.024	0.1	-10000	0	-0.29	45	45
Insulin Receptor/Insulin	0.01	0.082	0.24	1	-0.28	19	20
HCK	0.025	0.03	0.28	7	-10000	0	7
CRK	0.021	0.006	-10000	0	-10000	0	0
TYK2	-0.005	0.092	0.23	20	-0.29	25	45
EGF	0.03	0.057	0.28	21	-0.35	2	23
YES1	0.022	0.005	-10000	0	-10000	0	0
CAV1	-0.028	0.11	0.26	4	-0.32	37	41
TXN	0.022	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.01	0.1	-10000	0	-0.28	45	45
cell migration	0.014	0.088	0.3	30	-0.3	1	31
STAT3	0.022	0.006	-10000	0	-10000	0	0
PRLR	-0.05	0.15	-10000	0	-0.35	104	104
ITGA2B	0.017	0.041	0.28	1	-0.35	6	7
CSF1R	0.021	0.03	0.28	1	-0.35	3	4
Prolactin Receptor/Prolactin	-0.028	0.12	0.21	4	-0.25	114	118
FGR	0.016	0.051	-10000	0	-0.35	10	10
PTP1B/p130 Cas	-0.003	0.085	0.27	1	-0.28	30	31
Crk/p130 Cas	0.005	0.087	0.27	1	-0.29	23	24
DOK1	-0.018	0.098	0.23	3	-0.33	30	33
JAK2	-0.055	0.15	0.26	1	-0.37	66	67
Jak2/Leptin Receptor/Leptin	-0.011	0.095	-10000	0	-0.32	24	24
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
PTPN1	-0.014	0.089	0.3	1	-0.3	30	31
LYN	0.021	0.007	-10000	0	-10000	0	0
CDH2	-0.028	0.13	-10000	0	-0.35	73	73
SRC	0	0.11	-10000	0	-0.52	20	20
ITGB3	-0.04	0.14	0.28	2	-0.35	90	92
CAT1/PTP1B	-0.003	0.12	0.29	13	-0.38	22	35
CAPN1	0.022	0.004	-10000	0	-10000	0	0
CSK	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.013	0.078	-10000	0	-0.29	13	13
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.009	0.087	-10000	0	-0.31	20	20
negative regulation of transcription	-0.055	0.15	0.26	1	-0.36	66	67
FCGR2A	0.02	0.014	0.28	1	-10000	0	1
FER	0.023	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.017	0.11	0.21	3	-0.25	96	99
BLK	0.037	0.068	0.28	38	-10000	0	38
Insulin Receptor/Insulin/Shc	0.032	0.019	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
LEPR	-0.086	0.17	-10000	0	-0.35	158	158
BCAR1	0.021	0.007	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.022	0.006	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	0.008	0.11	0.26	12	-0.41	17	29
PRL	0.006	0.071	0.28	5	-0.35	17	22
SOCS3	0.001	0.16	-10000	0	-1.1	11	11
SPRY2	0.019	0.033	-10000	0	-0.36	4	4
Insulin Receptor/Insulin/IRS1	0.015	0.075	-10000	0	-0.21	51	51
CSF1/CSF1R	0.001	0.096	-10000	0	-0.28	33	33
Ras protein signal transduction	0.02	0.12	0.56	24	-10000	0	24
IRS1	-0.013	0.11	-10000	0	-0.35	51	51
INS	0.009	0.015	-10000	0	-10000	0	0
LEP	0.016	0.021	0.28	2	-10000	0	2
STAT5B	-0.033	0.12	0.29	1	-0.37	43	44
STAT5A	-0.032	0.12	0.29	1	-0.36	44	45
GRB2	0.022	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.01	0.096	-10000	0	-0.3	35	35
CSN2	-0.022	0.078	-10000	0	-0.5	2	2
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
LAT	0.008	0.091	-10000	0	-0.54	12	12
YBX1	0.026	0.017	-10000	0	-0.35	1	1
LCK	0.024	0.028	0.28	4	-0.35	1	5
SHC1	0.019	0.009	-10000	0	-10000	0	0
NOX4	0.02	0.034	0.28	1	-0.35	4	5

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.008	0.12	-10000	0	-0.41	39	39
HDAC1	0.021	0.007	-10000	0	-10000	0	0
AES	0.021	0.006	-10000	0	-10000	0	0
FBXW11	0.023	0.004	-10000	0	-10000	0	0
DTX1	0.019	0.039	-10000	0	-0.35	6	6
LRP6/FZD1	0.032	0.018	-10000	0	-0.25	2	2
TLE1	0.022	0.006	-10000	0	-10000	0	0
AP1	-0.048	0.11	-10000	0	-0.22	136	136
NCSTN	0.019	0.009	-10000	0	-10000	0	0
ADAM10	0.02	0.028	-10000	0	-0.35	3	3
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.006	0.15	-10000	0	-0.67	24	24
NICD/RBPSUH	-0.005	0.12	-10000	0	-0.4	38	38
WIF1	0.059	0.15	0.28	127	-0.35	34	161
NOTCH1	-0.007	0.099	-10000	0	-0.42	29	29
PSENEN	0.022	0.005	-10000	0	-10000	0	0
KREMEN2	0.045	0.073	0.28	47	-10000	0	47
DKK1	0.069	0.12	0.28	109	-0.35	8	117
beta catenin/beta TrCP1	0.029	0.069	0.23	1	-0.41	4	5
APH1B	0.018	0.039	-10000	0	-0.35	6	6
APH1A	0.019	0.009	-10000	0	-10000	0	0
AXIN1	-0.012	0.11	-10000	0	-0.45	22	22
CtBP/CBP/TCF1/TLE1/AES	0.01	0.039	-10000	0	-0.2	1	1
PSEN1	0.022	0.004	-10000	0	-10000	0	0
FOS	-0.089	0.17	-10000	0	-0.35	160	160
JUN	0.018	0.042	-10000	0	-0.35	7	7
MAP3K7	0.022	0.004	-10000	0	-10000	0	0
CTNNB1	0.018	0.07	0.23	2	-0.4	5	7
MAPK3	0.022	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.042	0.077	0.21	43	-0.2	30	73
HNF1A	0.026	0.031	0.28	8	-10000	0	8
CTBP1	0.022	0.005	-10000	0	-10000	0	0
MYC	-0.005	0.17	-10000	0	-1.2	11	11
NKD1	0.034	0.081	0.28	38	-0.35	8	46
FZD1	0.021	0.023	-10000	0	-0.35	2	2
NOTCH1 precursor/Deltex homolog 1	-0.007	0.12	-10000	0	-0.4	36	36
apoptosis	-0.047	0.11	-10000	0	-0.22	136	136
Delta 1/NOTCHprecursor	-0.01	0.12	-10000	0	-0.41	39	39
DLL1	0.01	0.067	-10000	0	-0.35	18	18
PPARD	0.017	0.058	-10000	0	-0.88	2	2
Gamma Secretase	0.045	0.04	-10000	0	-0.18	6	6
APC	-0.01	0.11	-10000	0	-0.53	17	17
DVL1	0.011	0.034	-10000	0	-0.37	3	3
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.083	0.084	0.21	144	-0.2	8	152
LRP6	0.023	0.003	-10000	0	-10000	0	0
CSNK1A1	0.023	0.004	-10000	0	-10000	0	0
NLK	0.009	0.005	-10000	0	-10000	0	0
CCND1	0.009	0.11	-10000	0	-0.85	8	8
WNT1	0.025	0.029	0.28	7	-10000	0	7
Axin1/APC/beta catenin	0.016	0.12	0.25	3	-0.43	22	25
DKK2	0.002	0.087	0.28	2	-0.35	30	32
NOTCH1 precursor/DVL1	-0.013	0.13	-10000	0	-0.51	26	26
GSK3B	0.022	0.004	-10000	0	-10000	0	0
FRAT1	0.022	0.005	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.005	0.12	-10000	0	-0.4	36	36
PPP2R5D	0.014	0.033	0.26	1	-0.29	2	3
MAPK1	0.022	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.076	0.097	0.36	3	-0.19	34	37
RBPJ	0.022	0.004	-10000	0	-10000	0	0
CREBBP	0.023	0.007	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.059	0.13	0.28	85	-0.34	20	105
FYN	0.028	0.12	0.26	27	-0.38	23	50
LAT/GRAP2/SLP76	0.031	0.11	0.3	10	-0.35	25	35
IKBKB	0.021	0.007	-10000	0	-10000	0	0
AKT1	0.019	0.1	0.26	18	-0.31	28	46
B2M	0.023	0.008	-10000	0	-10000	0	0
IKBKG	0.009	0.036	0.13	12	-0.11	12	24
MAP3K8	0.02	0.028	-10000	0	-0.35	3	3
mol:Ca2+	-0.013	0.012	0.086	1	-0.078	4	5
integrin-mediated signaling pathway	0.026	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.017	0.14	0.31	14	-0.42	30	44
TRPV6	-0.015	0.18	1.2	9	-10000	0	9
CD28	0.024	0.017	0.28	2	-10000	0	2
SHC1	0.045	0.15	0.29	86	-0.38	24	110
receptor internalization	0.017	0.12	0.28	8	-0.4	30	38
PRF1	0.01	0.17	0.42	4	-0.82	15	19
KRAS	0.023	0.014	0.33	1	-10000	0	1
GRB2	0.022	0.006	-10000	0	-10000	0	0
COT/AKT1	0.027	0.09	0.26	14	-0.26	24	38
LAT	0.021	0.12	0.28	16	-0.38	27	43
EntrezGene:6955	0	0.003	-10000	0	-0.034	1	1
CD3D	0.025	0.061	0.29	14	-0.36	7	21
CD3E	0.02	0.056	0.3	5	-0.36	9	14
CD3G	0.024	0.039	0.29	7	-0.35	2	9
RASGRP2	-0.014	0.058	0.084	2	-0.16	74	76
RASGRP1	0.013	0.12	0.28	19	-0.35	27	46
HLA-A	0.001	0.003	-10000	0	-10000	0	0
RASSF5	0.02	0.008	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.027	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.027	0.067	0.15	77	-0.12	20	97
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.005	0.04	-10000	0	-0.17	22	22
PRKCA	0.004	0.066	0.18	15	-0.2	18	33
GRAP2	0.011	0.061	-10000	0	-0.35	15	15
mol:IP3	0.014	0.086	0.2	38	-0.28	21	59
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.007	0.082	0.27	6	-0.42	13	19
ORAI1	0	0.15	0.4	3	-0.98	9	12
CSK	0.02	0.12	0.26	13	-0.37	29	42
B7 family/CD28	0.053	0.12	0.41	11	-0.39	17	28
CHUK	0.022	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.017	0.13	0.27	11	-0.4	32	43
PTPN6	0.016	0.12	0.25	16	-0.36	29	45
VAV1	0.019	0.12	0.29	10	-0.39	26	36
Monovalent TCR/CD3	0.011	0.053	0.23	8	-0.26	13	21
CBL	0.022	0.005	-10000	0	-10000	0	0
LCK	0.026	0.13	0.26	26	-0.39	24	50
PAG1	0.025	0.12	0.28	14	-0.37	27	41
RAP1A	0.023	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.017	0.13	0.25	15	-0.39	31	46
CD80	0.036	0.059	0.28	29	-10000	0	29
CD86	0.024	0.017	0.29	2	-10000	0	2
PDK1/CARD11/BCL10/MALT1	0.004	0.052	0.16	2	-0.2	23	25
HRAS	0.022	0.005	-10000	0	-10000	0	0
GO:0035030	0.018	0.094	0.27	11	-0.34	17	28
CD8A	0.02	0.052	0.3	4	-0.36	8	12
CD8B	0.031	0.071	0.28	25	-0.36	7	32
PTPRC	0.015	0.047	0.28	1	-0.35	8	9
PDK1/PKC theta	0.015	0.12	0.29	21	-0.37	27	48
CSK/PAG1	0.025	0.12	0.29	16	-0.38	24	40
SOS1	0.023	0.003	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.008	-10000	0	-10000	0	0
GRAP2/SLP76	0.034	0.12	0.36	6	-0.4	26	32
STIM1	0.002	0.062	1.2	1	-10000	0	1
RAS family/GTP	0.036	0.072	0.2	29	-0.16	16	45
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.016	0.12	0.31	6	-0.42	30	36
mol:DAG	-0.004	0.062	0.096	6	-0.24	26	32
RAP1A/GDP	0.015	0.032	0.085	33	-0.062	11	44
PLCG1	0.022	0.005	-10000	0	-10000	0	0
CD247	0.019	0.027	0.3	1	-0.35	2	3
cytotoxic T cell degranulation	0.011	0.16	0.41	4	-0.78	15	19
RAP1A/GTP	-0.006	0.022	-10000	0	-0.059	76	76
mol:PI-3-4-5-P3	0.019	0.12	0.28	18	-0.36	30	48
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.028	0.11	0.22	36	-0.34	21	57
NRAS	0.023	0.001	-10000	0	-10000	0	0
ZAP70	0.03	0.05	0.28	16	-0.35	2	18
GRB2/SOS1	0.032	0.009	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	0.022	0.1	0.32	5	-0.34	24	29
MALT1	0.022	0.005	-10000	0	-10000	0	0
TRAF6	0.022	0.005	-10000	0	-10000	0	0
CD8 heterodimer	0.038	0.069	0.24	26	-0.27	14	40
CARD11	0.027	0.042	0.28	12	-0.35	1	13
PRKCB	0.004	0.072	0.18	17	-0.23	23	40
PRKCE	0.009	0.062	0.18	15	-0.2	17	32
PRKCQ	0.014	0.13	0.3	18	-0.4	30	48
LCP2	0.023	0.012	0.28	1	-10000	0	1
BCL10	0.023	0.002	-10000	0	-10000	0	0
regulation of survival gene product expression	0.02	0.095	0.24	21	-0.27	27	48
IKK complex	0.015	0.058	0.19	27	-0.11	10	37
RAS family/GDP	-0.001	0.009	-10000	0	-0.039	7	7
MAP3K14	0.019	0.07	0.2	16	-0.21	21	37
PDPK1	0.019	0.1	0.27	17	-0.3	27	44
TCR/CD3/MHC I/CD8/Fyn	-0.006	0.15	0.39	4	-0.49	33	37

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.013	0.1	0.21	2	-0.24	89	91
AKT1	-0.015	0.15	0.33	6	-0.48	37	43
PTK2B	-0.055	0.13	-10000	0	-0.5	31	31
VEGFR2 homodimer/Frs2	-0.006	0.13	-10000	0	-0.53	31	31
CAV1	-0.04	0.14	-10000	0	-0.35	89	89
CALM1	0.022	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.009	0.12	-10000	0	-0.49	31	31
endothelial cell proliferation	-0.021	0.15	0.34	15	-0.44	44	59
mol:Ca2+	-0.044	0.12	0.18	4	-0.49	32	36
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.019	0.12	-10000	0	-0.46	31	31
RP11-342D11.1	-0.042	0.12	0.17	6	-0.49	32	38
CDH5	0.016	0.04	-10000	0	-0.35	6	6
VEGFA homodimer	0.044	0.029	-10000	0	-0.19	1	1
SHC1	0.019	0.009	-10000	0	-10000	0	0
SHC2	-0.025	0.12	-10000	0	-0.35	67	67
HRAS/GDP	-0.004	0.11	-10000	0	-0.43	30	30
SH2D2A	0.029	0.053	0.29	21	-10000	0	21
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.002	0.14	-10000	0	-0.44	36	36
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.009	0.12	0.22	3	-0.47	31	34
VEGFR1 homodimer	0.022	0.005	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.009	0.13	-10000	0	-0.47	30	30
GRB10	-0.044	0.12	-10000	0	-0.51	31	31
PTPN11	0.023	0.003	-10000	0	-10000	0	0
GRB2	0.022	0.006	-10000	0	-10000	0	0
PAK1	0.022	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.025	0.13	-10000	0	-0.48	30	30
HRAS	0.022	0.005	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.03	0.11	-10000	0	-0.35	37	37
HIF1A	0.023	0.004	-10000	0	-10000	0	0
FRS2	0.023	0.003	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.018	0.12	-10000	0	-0.46	31	31
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.009	0.069	-10000	0	-0.35	19	19
Nck/Pak	0.031	0.019	-10000	0	-0.25	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.009	0.12	-10000	0	-0.48	31	31
mol:GDP	0.002	0.12	-10000	0	-0.45	30	30
mol:NADP	-0.008	0.12	0.33	8	-0.38	37	45
eNOS/Hsp90	0	0.12	0.35	6	-0.37	36	42
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
mol:IP3	-0.045	0.12	0.18	4	-0.5	32	36
HIF1A/ARNT	0.026	0.015	-10000	0	-10000	0	0
SHB	0.022	0.004	-10000	0	-10000	0	0
VEGFA	0.023	0.004	-10000	0	-10000	0	0
VEGFC	0.017	0.045	-10000	0	-0.35	8	8
FAK1/Vinculin	-0.029	0.16	0.26	3	-0.56	32	35
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.015	0.15	-10000	0	-0.5	33	33
PTPN6	0.023	0.014	0.33	1	-10000	0	1
EPAS1	0.008	0.078	-10000	0	-0.31	31	31
mol:L-citrulline	-0.008	0.12	0.33	8	-0.38	37	45
ITGAV	0.023	0.003	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.02	0.12	-10000	0	-0.44	31	31
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.14	-10000	0	-0.53	32	32
VEGFR2/3 heterodimer	-0.014	0.14	-10000	0	-0.43	47	47
VEGFB	0.022	0.004	-10000	0	-10000	0	0
MAPK11	-0.041	0.14	0.31	3	-0.51	35	38
VEGFR2 homodimer	-0.021	0.14	-10000	0	-0.61	30	30
FLT1	0.022	0.005	-10000	0	-10000	0	0
NEDD4	-0.003	0.094	-10000	0	-0.35	37	37
MAPK3	-0.04	0.13	0.29	11	-0.44	37	48
MAPK1	-0.041	0.13	0.29	10	-0.44	37	47
VEGFA145/NRP2	0.021	0.058	-10000	0	-0.24	24	24
VEGFR1/2 heterodimer	-0.006	0.13	-10000	0	-0.53	31	31
KDR	-0.021	0.14	-10000	0	-0.61	30	30
VEGFA165/NRP1/VEGFR2 homodimer	-0.009	0.14	-10000	0	-0.49	35	35
SRC	0.022	0.005	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.041	0.14	0.29	11	-0.44	39	50
PI3K	-0.017	0.14	-10000	0	-0.54	31	31
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.008	0.12	-10000	0	-0.48	31	31
FES	-0.046	0.13	0.18	6	-0.5	33	39
GAB1	-0.004	0.15	-10000	0	-0.54	32	32
VEGFR2 homodimer/VEGFA homodimer/Src	0.008	0.12	-10000	0	-0.48	31	31
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
SOS1	0.023	0.003	-10000	0	-10000	0	0
ARNT	0.018	0.01	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.019	0.14	0.31	4	-0.42	37	41
VEGFR2 homodimer/VEGFA homodimer/Yes	0.008	0.12	-10000	0	-0.48	31	31
PI3K/GAB1	-0.002	0.14	-10000	0	-0.5	32	32
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.03	0.12	-10000	0	-0.43	31	31
PRKACA	0.022	0.005	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.003	0.14	-10000	0	-0.39	52	52
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
CDC42	-0.045	0.12	0.18	6	-0.5	32	38
actin cytoskeleton reorganization	0.009	0.12	0.22	3	-0.47	31	34
PTK2	-0.043	0.15	0.25	3	-0.6	31	34
EDG1	-0.042	0.12	0.17	6	-0.49	32	38
mol:DAG	-0.045	0.12	0.18	4	-0.5	32	36
CaM/Ca2+	-0.013	0.12	-10000	0	-0.46	32	32
MAP2K3	-0.041	0.11	-10000	0	-0.48	29	29
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.002	0.14	-10000	0	-0.52	32	32
PLCG1	-0.045	0.12	0.18	4	-0.5	32	36
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.019	0.12	-10000	0	-0.46	31	31
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
YES1	0.022	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.009	0.12	-10000	0	-0.49	31	31
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.009	0.12	-10000	0	-0.49	31	31
cell migration	-0.027	0.14	0.26	2	-0.5	34	36
mol:PI-3-4-5-P3	-0.015	0.13	-10000	0	-0.5	31	31
FYN	0.023	0.004	-10000	0	-10000	0	0
VEGFB/NRP1	-0.02	0.12	-10000	0	-0.46	32	32
mol:NO	-0.008	0.12	0.33	8	-0.38	37	45
PXN	0.023	0.003	-10000	0	-10000	0	0
HRAS/GTP	-0.014	0.11	-10000	0	-0.43	30	30
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.011	0.14	-10000	0	-0.52	32	32
VHL	0.022	0.017	-10000	0	-0.35	1	1
ITGB3	-0.04	0.14	0.28	2	-0.35	90	92
NOS3	-0.011	0.14	0.36	6	-0.43	37	43
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.02	0.14	-10000	0	-0.49	32	32
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCA	-0.051	0.12	-10000	0	-0.47	34	34
PRKCB	-0.051	0.12	-10000	0	-0.48	34	34
VCL	0.022	0.005	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.018	0.13	-10000	0	-0.49	32	32
VEGFR1/2 heterodimer/VEGFA homodimer	0.008	0.12	-10000	0	-0.48	31	31
VEGFA165/NRP2	0.021	0.058	-10000	0	-0.24	24	24
MAPKKK cascade	-0.013	0.13	0.33	2	-0.46	27	29
NRP2	0.006	0.077	-10000	0	-0.35	24	24
VEGFC homodimer	0.017	0.045	-10000	0	-0.35	8	8
NCK1	0.021	0.023	-10000	0	-0.35	2	2
ROCK1	0.023	0.004	-10000	0	-10000	0	0
FAK1/Paxillin	-0.03	0.16	0.26	3	-0.55	33	36
MAP3K13	-0.043	0.12	0.18	4	-0.5	30	34
PDPK1	-0.024	0.12	0.25	1	-0.45	31	32

×

TCGA08_rtk_signaling

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
PDGFRA	-0.075	0.16	-10000	0	-0.35	141	141
HRAS	0.022	0.005	-10000	0	-10000	0	0
EGFR	0.014	0.059	0.33	1	-0.35	13	14
AKT	-0.041	0.13	0.29	4	-0.25	125	129
FOXO3	0.023	0.003	-10000	0	-10000	0	0
AKT1	0.023	0.004	-10000	0	-10000	0	0
FOXO1	0.021	0.023	-10000	0	-0.35	2	2
AKT3	-0.096	0.17	-10000	0	-0.35	166	166
FOXO4	0.022	0.023	-10000	0	-0.35	2	2
MET	0.021	0.042	0.28	4	-0.35	5	9
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
PIK3CB	0.022	0.005	-10000	0	-10000	0	0
NRAS	0.023	0.001	-10000	0	-10000	0	0
PIK3CG	0.013	0.062	0.28	2	-0.35	14	16
PIK3R3	0.023	0.012	0.28	1	-10000	0	1
PIK3R2	0.022	0.005	-10000	0	-10000	0	0
NF1	0.021	0.006	-10000	0	-10000	0	0
RAS	-0.011	0.066	0.16	9	-0.13	106	115
ERBB2	0.029	0.049	0.33	14	-10000	0	14
proliferation/survival/translation	0.004	0.088	0.27	15	-0.28	5	20
PI3K	0.003	0.07	0.21	20	-0.22	9	29
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
KRAS	0.023	0.014	0.33	1	-10000	0	1
FOXO	0.032	0.048	0.24	7	-10000	0	7
AKT2	0.022	0.005	-10000	0	-10000	0	0
PTEN	0.021	0.006	-10000	0	-10000	0	0

×

Insulin 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
CBL/APS/CAP	-0.041	0.12	-10000	0	-0.2	175	175
TC10/GTP	-0.026	0.094	-10000	0	-0.17	155	155
Insulin Receptor/Insulin/IRS1/Shp2	0.028	0.075	-10000	0	-0.19	51	51
HRAS	0.022	0.005	-10000	0	-10000	0	0
APS homodimer	0.022	0.005	-10000	0	-10000	0	0
GRB14	0.11	0.13	0.28	190	-0.35	3	193
FOXO3	0.016	0.066	-10000	0	-0.57	6	6
AKT1	-0.006	0.079	0.24	14	-0.3	2	16
INSR	0.024	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.045	0.032	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.022	0.017	-10000	0	-0.35	1	1
SORBS1	-0.096	0.17	-10000	0	-0.35	170	170
CRK	0.021	0.006	-10000	0	-10000	0	0
PTPN1	-0.004	0.027	0.15	16	-10000	0	16
CAV1	-0.05	0.088	0.16	5	-0.21	107	112
CBL/APS/CAP/Crk-II/C3G	-0.017	0.11	-10000	0	-0.18	158	158
Insulin Receptor/Insulin/IRS1/NCK2	0.029	0.075	-10000	0	-0.19	51	51
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.019	0.063	-10000	0	-0.18	44	44
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.008	0.089	-10000	0	-0.32	28	28
RPS6KB1	-0.012	0.072	0.23	13	-0.28	2	15
PARD6A	0.021	0.007	-10000	0	-10000	0	0
CBL	0.022	0.005	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.014	0.027	-10000	0	-0.57	1	1
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.007	0.064	-10000	0	-0.29	2	2
HRAS/GTP	-0.025	0.038	-10000	0	-0.17	28	28
Insulin Receptor	0.024	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.033	0.064	-10000	0	-0.18	33	33
PRKCI	0.005	0.07	-10000	0	-0.38	1	1
Insulin Receptor/Insulin/GRB14/PDK1	0.021	0.065	-10000	0	-0.17	40	40
SHC1	0.019	0.009	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.034	0.041	-10000	0	-0.35	4	4
PI3K	0.026	0.067	-10000	0	-0.18	44	44
NCK2	0.023	0.002	-10000	0	-10000	0	0
RHOQ	0.023	0.003	-10000	0	-10000	0	0
mol:H2O2	0	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.016	0.004	-10000	0	-10000	0	0
AKT2	-0.008	0.077	0.25	12	-0.3	2	14
PRKCZ	0.002	0.077	-10000	0	-0.3	14	14
SH2B2	0.022	0.005	-10000	0	-10000	0	0
SHC/SHIP	0.007	0.05	-10000	0	-0.17	33	33
F2RL2	0.003	0.088	0.28	3	-0.35	30	33
TRIP10	0.021	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.032	0.021	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.029	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.048	0.032	-10000	0	-10000	0	0
RAPGEF1	0.022	0.006	-10000	0	-10000	0	0
RASA1	0.019	0.036	-10000	0	-0.35	5	5
NCK1	0.021	0.023	-10000	0	-0.35	2	2
CBL/APS/CAP/Crk-II	-0.025	0.11	-10000	0	-0.19	163	163
TC10/GDP	0.017	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.042	0.029	-10000	0	-0.2	1	1
INPP5D	-0.027	0.053	0.15	4	-0.18	50	54
SOS1	0.023	0.003	-10000	0	-10000	0	0
SGK1	0.005	0.068	-10000	0	-0.7	5	5
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.023	0.003	-10000	0	-10000	0	0
IRS1	-0.013	0.11	-10000	0	-0.35	51	51
p62DOK/RasGAP	0.034	0.042	-10000	0	-0.36	4	4
INS	0.018	0.009	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.027	0.052	0.15	4	-0.18	50	54
GRB2	0.022	0.006	-10000	0	-10000	0	0
EIF4EBP1	-0.011	0.075	0.25	16	-0.28	2	18
PTPRA	0.024	0.007	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
TC10/GTP/CIP4	0.029	0.009	-10000	0	-10000	0	0
PDPK1	0.022	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.001	0.056	-10000	0	-0.19	40	40
Insulin Receptor/Insulin/IRS1	0.017	0.069	-10000	0	-0.19	51	51
Insulin Receptor/Insulin/IRS3	0.031	0.013	-10000	0	-10000	0	0
Par3/Par6	0.034	0.055	-10000	0	-0.18	28	28

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.01	0.005	-10000	0	-10000	0	0
SMARCC1	0.009	0.014	-10000	0	-10000	0	0
REL	0.021	0.009	-10000	0	-10000	0	0
HDAC7	-0.012	0.062	0.2	8	-0.26	8	16
JUN	0.018	0.042	-10000	0	-0.35	7	7
EP300	0.022	0.006	-10000	0	-10000	0	0
KAT2B	0.017	0.045	-10000	0	-0.35	8	8
KAT5	0.022	0.004	-10000	0	-10000	0	0
MAPK14	0.007	0.045	0.12	62	-10000	0	62
FOXO1	0.021	0.023	-10000	0	-0.35	2	2
T-DHT/AR	0.021	0.075	0.27	5	-0.26	8	13
MAP2K6	0.052	0.087	0.28	66	-10000	0	66
BRM/BAF57	0.025	0.043	-10000	0	-0.24	13	13
MAP2K4	0.018	0.02	-10000	0	-0.34	1	1
SMARCA2	0.013	0.06	-10000	0	-0.35	14	14
PDE9A	-0.003	0.1	-10000	0	-0.63	9	9
NCOA2	0.008	0.066	-10000	0	-0.35	17	17
CEBPA	0.021	0.032	0.28	2	-0.35	3	5
EHMT2	0.023	0.004	-10000	0	-10000	0	0
cell proliferation	0.003	0.14	0.35	19	-0.37	23	42
NR0B1	0.033	0.06	0.28	30	-10000	0	30
EGR1	-0.024	0.12	-10000	0	-0.35	68	68
RXRs/9cRA	0.012	0.075	0.21	8	-0.19	59	67
AR/RACK1/Src	0.002	0.074	0.22	11	-0.25	8	19
AR/GR	-0.038	0.12	0.21	3	-0.22	127	130
GNB2L1	0.021	0.009	-10000	0	-10000	0	0
PKN1	0.022	0.006	-10000	0	-10000	0	0
RCHY1	0.023	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-10000	0	-0.013	6	6
MAPK8	-0.009	0.024	-10000	0	-0.25	4	4
T-DHT/AR/TIF2/CARM1	0.009	0.074	0.22	2	-0.28	10	12
SRC	-0.003	0.05	0.18	29	-0.18	3	32
NR3C1	-0.031	0.13	-10000	0	-0.35	77	77
KLK3	0.023	0.11	0.39	2	-0.46	2	4
APPBP2	0.022	0.009	-10000	0	-10000	0	0
TRIM24	0.023	0.005	-10000	0	-10000	0	0
T-DHT/AR/TIP60	0.001	0.064	0.21	12	-0.25	4	16
TMPRSS2	-0.006	0.14	0.39	1	-0.8	13	14
RXRG	-0.018	0.12	0.31	9	-0.35	60	69
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.022	0.006	-10000	0	-10000	0	0
RXRB	0.023	0.003	-10000	0	-10000	0	0
CARM1	0.02	0.01	-10000	0	-10000	0	0
NR2C2	0.016	0.051	-10000	0	-0.35	10	10
KLK2	-0.015	0.13	-10000	0	-0.49	28	28
AR	-0.02	0.086	0.15	18	-0.22	74	92
SENP1	0.023	0.004	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
MDM2	0.021	0.009	-10000	0	-10000	0	0
SRY	-0.001	0.003	-10000	0	-0.016	19	19
GATA2	-0.012	0.11	-10000	0	-0.35	50	50
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	0.19	0.12	0.28	349	-10000	0	349
T-DHT/AR/RACK1/Src	-0.003	0.072	0.22	19	-0.23	6	25
positive regulation of transcription	-0.012	0.11	-10000	0	-0.35	50	50
DNAJA1	0.022	0.009	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.004	-10000	0	-10000	0	0
NCOA1	0.026	0.022	-10000	0	-0.38	1	1
SPDEF	0.083	0.15	0.28	160	-0.35	24	184
T-DHT/AR/TIF2	-0.002	0.093	0.23	14	-0.32	23	37
T-DHT/AR/Hsp90	0.003	0.065	0.21	13	-0.24	4	17
GSK3B	0.023	0.006	-10000	0	-10000	0	0
NR2C1	0.023	0.002	-10000	0	-10000	0	0
mol:T-DHT	-0.008	0.035	0.21	8	-0.19	3	11
SIRT1	0.021	0.023	-10000	0	-0.35	2	2
ZMIZ2	0.02	0.01	-10000	0	-10000	0	0
POU2F1	0.024	0.025	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	0.003	0.075	0.22	21	-0.27	3	24
CREBBP	0.022	0.005	-10000	0	-10000	0	0
SMARCE1	0.022	0.006	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.12	0.18	0.28	2	-0.35	209	211
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.023	0.012	0.28	1	-10000	0	1
TCEB1	0.021	0.007	-10000	0	-10000	0	0
HIF1A/p53	0.024	0.062	0.25	1	-0.26	17	18
HIF1A	0.007	0.056	-10000	0	-0.27	17	17
COPS5	0.021	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.056	0.03	-10000	0	-0.18	1	1
FIH (dimer)	0.022	0.005	-10000	0	-10000	0	0
CDKN2A	0.13	0.13	0.28	216	-10000	0	216
ARNT/IPAS	-0.058	0.12	0.21	2	-0.25	163	165
HIF1AN	0.022	0.005	-10000	0	-10000	0	0
GNB2L1	0.023	0.004	-10000	0	-10000	0	0
HIF1A/ARNT	0.01	0.052	-10000	0	-0.26	14	14
CUL2	0.022	0.004	-10000	0	-10000	0	0
OS9	0.023	0.001	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.041	0.018	0.2	1	-10000	0	1
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.023	0.062	-10000	0	-0.26	18	18
PHD1-3/OS9	0.047	0.03	0.21	3	-0.19	1	4
HIF1A/RACK1/Elongin B/Elongin C	0.038	0.06	0.23	1	-0.25	15	16
VHL	0.022	0.017	-10000	0	-0.35	1	1
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
HIF1A/JAB1	0.022	0.058	-10000	0	-0.26	14	14
EGLN3	0.023	0.025	0.28	3	-0.35	1	4
EGLN2	0.022	0.005	-10000	0	-10000	0	0
EGLN1	0.02	0.009	-10000	0	-10000	0	0
TP53	0.021	0.006	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.017	0.1	-10000	0	-0.54	16	16
ARNT	0.018	0.01	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.022	0.006	-10000	0	-10000	0	0
HIF1A/p19ARF	0.082	0.1	0.25	40	-0.26	17	57

×

Canonical Wnt signaling pathway

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
HDAC1	0.026	0.024	0.22	4	-10000	0	4
AES	0.024	0.021	0.19	4	-10000	0	4
FBXW11	0.023	0.004	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.032	0.019	-10000	0	-0.25	2	2
SMAD4	0.022	0.005	-10000	0	-10000	0	0
DKK2	0.002	0.087	0.28	2	-0.35	30	32
TLE1	0.024	0.021	0.2	4	-10000	0	4
MACF1	0.022	0.004	-10000	0	-10000	0	0
CTNNB1	0.009	0.082	0.31	7	-0.34	8	15
WIF1	0.059	0.15	0.28	127	-0.35	34	161
beta catenin/RanBP3	0.016	0.12	0.41	31	-0.34	3	34
KREMEN2	0.045	0.074	0.28	47	-10000	0	47
DKK1	0.069	0.12	0.28	109	-0.35	8	117
beta catenin/beta TrCP1	0.017	0.079	0.29	6	-0.31	8	14
FZD1	0.021	0.023	-10000	0	-0.35	2	2
AXIN2	-0.046	0.28	0.65	10	-1.2	27	37
AXIN1	0.022	0.005	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.11	-10000	0	-0.54	19	19
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.025	0.18	0.3	2	-0.57	39	41
Axin1/APC/GSK3	0.006	0.057	0.25	3	-0.32	4	7
Axin1/APC/GSK3/beta catenin/Macf1	0.011	0.065	0.29	4	-0.34	8	12
HNF1A	0.029	0.037	0.26	11	-10000	0	11
CTBP1	0.024	0.02	0.2	3	-10000	0	3
MYC	0.066	0.27	0.59	79	-1.1	10	89
RANBP3	0.022	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.042	0.077	0.21	43	-0.2	30	73
NKD1	0.034	0.082	0.28	38	-0.35	8	46
TCF4	0.012	0.07	0.2	4	-0.35	18	22
TCF3	0.024	0.022	0.2	4	-10000	0	4
WNT1/LRP6/FZD1/Axin1	0.055	0.027	-10000	0	-0.19	2	2
Ran/GTP	0.017	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.004	0.14	0.47	22	-0.43	14	36
LEF1	0.023	0.039	0.22	5	-0.33	4	9
DVL1	0.009	0.06	0.24	2	-0.53	4	6
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.037	0.19	-10000	0	-0.58	43	43
DKK1/LRP6/Kremen 2	0.083	0.084	0.21	144	-0.2	8	152
LRP6	0.023	0.003	-10000	0	-10000	0	0
CSNK1A1	0.025	0.022	0.22	3	-10000	0	3
NLK	0.02	0.011	-10000	0	-10000	0	0
CCND1	0.002	0.1	0.58	9	-0.6	3	12
WNT1	0.024	0.03	0.28	7	-10000	0	7
GSK3A	0.023	0.004	-10000	0	-10000	0	0
GSK3B	0.023	0.004	-10000	0	-10000	0	0
FRAT1	0.022	0.006	-10000	0	-10000	0	0
PPP2R5D	0.015	0.046	0.26	6	-0.27	3	9
APC	-0.01	0.041	0.18	21	-0.18	1	22
WNT1/LRP6/FZD1	0.003	0.06	0.18	28	-0.2	6	34
CREBBP	0.024	0.021	0.2	3	-10000	0	3

×

IL2 signaling events mediated by STAT5

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
GAB2	0.02	0.032	-10000	0	-0.35	4	4
ELF1	0.026	0.042	-10000	0	-0.34	5	5
CCNA2	0.077	0.1	0.28	114	-10000	0	114
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
JAK3	0.024	0.023	0.28	4	-10000	0	4
PIK3R1	0.019	0.036	-10000	0	-0.35	5	5
JAK1	0.023	0.016	-10000	0	-0.35	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.039	0.076	-10000	0	-0.44	4	4
SHC1	0.019	0.009	-10000	0	-10000	0	0
SP1	-0.035	0.13	-10000	0	-0.31	98	98
IL2RA	0.016	0.052	0.21	20	-0.32	5	25
IL2RB	0.021	0.017	-10000	0	-0.35	1	1
SOS1	0.023	0.003	-10000	0	-10000	0	0
IL2RG	0.024	0.039	0.28	6	-0.35	3	9
G1/S transition of mitotic cell cycle	-0.088	0.27	0.28	4	-0.61	99	103
PTPN11	0.023	0.003	-10000	0	-10000	0	0
CCND2	-0.095	0.23	-10000	0	-0.61	92	92
LCK	0.024	0.028	0.28	4	-0.35	1	5
GRB2	0.022	0.006	-10000	0	-10000	0	0
IL2	0.027	0.046	0.28	17	-10000	0	17
CDK6	0.014	0.055	-10000	0	-0.35	12	12
CCND3	0.039	0.081	0.35	2	-0.46	2	4

×

BARD1 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
BARD1/CSTF1	0.026	0.04	-10000	0	-0.25	11	11
ATM	0.022	0.005	-10000	0	-10000	0	0
UBE2D3	0.022	0.004	-10000	0	-10000	0	0
PRKDC	0.021	0.007	-10000	0	-10000	0	0
ATR	0.022	0.004	-10000	0	-10000	0	0
UBE2L3	0.022	0.005	-10000	0	-10000	0	0
FANCD2	0.015	0.011	0.24	1	-10000	0	1
protein ubiquitination	0.093	0.079	0.21	36	-0.17	10	46
XRCC5	0.023	0.003	-10000	0	-10000	0	0
XRCC6	0.022	0.006	-10000	0	-10000	0	0
M/R/N Complex	0.041	0.016	-10000	0	-10000	0	0
MRE11A	0.022	0.004	-10000	0	-10000	0	0
DNA-PK	0.04	0.017	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.01	0.095	-10000	0	-0.46	13	13
FANCF	0.021	0.023	-10000	0	-0.35	2	2
BRCA1	0.022	0.006	-10000	0	-10000	0	0
CCNE1	0.13	0.13	0.29	217	-10000	0	217
CDK2/Cyclin E1	0.1	0.089	0.22	207	-10000	0	207
FANCG	0.022	0.005	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.026	0.04	-10000	0	-0.25	11	11
FANCE	0.023	0.004	-10000	0	-10000	0	0
FANCC	0.022	0.006	-10000	0	-10000	0	0
NBN	0.021	0.007	-10000	0	-10000	0	0
FANCA	0.079	0.11	0.28	123	-10000	0	123
DNA repair	0.012	0.078	0.27	7	-0.36	8	15
BRCA1/BARD1/ubiquitin	0.026	0.04	-10000	0	-0.25	11	11
BARD1/DNA-PK	0.045	0.041	-10000	0	-0.19	11	11
FANCL	0.023	0.003	-10000	0	-10000	0	0
mRNA polyadenylation	-0.026	0.04	0.24	11	-10000	0	11
BRCA1/BARD1/CTIP/M/R/N Complex	0.011	0.049	-10000	0	-0.2	21	21
BRCA1/BACH1/BARD1/TopBP1	0.038	0.038	-10000	0	-0.21	11	11
BRCA1/BARD1/P53	0.046	0.04	-10000	0	-0.19	11	11
BARD1/CSTF1/BRCA1	0.037	0.038	-10000	0	-0.21	11	11
BRCA1/BACH1	0.022	0.006	-10000	0	-10000	0	0
BARD1	0.015	0.053	-10000	0	-0.35	11	11
PCNA	0.022	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.038	0.038	-10000	0	-0.21	11	11
BRCA1/BARD1/UbcH7	0.037	0.038	-10000	0	-0.21	11	11
BRCA1/BARD1/RAD51/PCNA	0.084	0.081	0.21	133	-0.18	11	144
BARD1/DNA-PK/P53	0.051	0.043	-10000	0	-0.18	11	11
BRCA1/BARD1/Ubiquitin	0.026	0.04	-10000	0	-0.25	11	11
BRCA1/BARD1/CTIP	0.028	0.034	-10000	0	-0.19	11	11
FA complex	0.025	0.059	0.24	2	-0.28	3	5
BARD1/EWS	0.026	0.04	-10000	0	-0.25	11	11
RBBP8	-0.011	0.003	-10000	0	-10000	0	0
TP53	0.021	0.006	-10000	0	-10000	0	0
TOPBP1	0.023	0.004	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.045	0.039	0.19	11	-10000	0	11
BRCA1/BARD1	0.1	0.084	0.23	36	-0.18	10	46
CSTF1	0.022	0.005	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.012	0.037	-10000	0	-0.24	11	11
CDK2	0.023	0.004	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.099	0.12	0.28	160	-10000	0	160
RAD50	0.023	0.003	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.026	0.04	-10000	0	-0.25	11	11
EWSR1	0.022	0.006	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.023	0.004	-10000	0	-10000	0	0
HDAC2	0.023	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.038	0.039	0.2	1	-0.21	11	12
forebrain development	-0.093	0.21	-10000	0	-0.48	103	103
GNAO1	-0.066	0.16	-10000	0	-0.35	124	124
SMO/beta Arrestin2	0.026	0.03	-10000	0	-0.24	4	4
SMO	0.017	0.034	-10000	0	-0.35	4	4
ARRB2	0.02	0.01	-10000	0	-10000	0	0
GLI3/SPOP	-0.036	0.13	-10000	0	-0.42	16	16
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.022	0.004	-10000	0	-10000	0	0
GNAI2	0.021	0.007	-10000	0	-10000	0	0
SIN3/HDAC complex	0.052	0.021	-10000	0	-10000	0	0
GNAI1	0.017	0.045	-10000	0	-0.35	8	8
XPO1	0.021	0.012	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.065	0.18	-10000	0	-0.55	44	44
SAP30	0.022	0.004	-10000	0	-10000	0	0
mol:GDP	0.017	0.034	-10000	0	-0.35	4	4
MIM/GLI2A	0.015	0.032	-10000	0	-10000	0	0
IFT88	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.005	-10000	0	-10000	0	0
GLI2	-0.037	0.099	0.18	1	-0.34	22	23
GLI3	-0.044	0.13	-10000	0	-0.45	16	16
CSNK1D	0.022	0.006	-10000	0	-10000	0	0
CSNK1E	0.022	0.006	-10000	0	-10000	0	0
SAP18	0.022	0.005	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.022	0.005	-10000	0	-10000	0	0
GNG2	0.017	0.049	0.28	1	-0.35	9	10
Gi family/GTP	-0.043	0.11	-10000	0	-0.22	124	124
SIN3B	0.022	0.006	-10000	0	-10000	0	0
SIN3A	0.022	0.005	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.026	0.11	-10000	0	-0.4	18	18
GLI2/Su(fu)	-0.029	0.1	-10000	0	-0.32	33	33
FOXA2	-0.075	0.29	-10000	0	-0.92	54	54
neural tube patterning	-0.093	0.21	-10000	0	-0.48	103	103
SPOP	0.022	0.005	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.021	0.036	-10000	0	-10000	0	0
GNB1	0.022	0.004	-10000	0	-10000	0	0
CSNK1G2	0.021	0.006	-10000	0	-10000	0	0
CSNK1G3	0.023	0.004	-10000	0	-10000	0	0
MTSS1	0.015	0.032	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.093	0.21	-10000	0	-0.48	103	103
SUFU	0.013	0.016	-10000	0	-10000	0	0
LGALS3	0.021	0.023	-10000	0	-0.35	2	2
catabolic process	-0.06	0.15	-10000	0	-0.33	74	74
GLI3A/CBP	-0.03	0.12	-10000	0	-0.31	88	88
KIF3A	0.022	0.016	-10000	0	-0.35	1	1
GLI1	-0.096	0.21	-10000	0	-0.49	103	103
RAB23	0.019	0.036	-10000	0	-0.35	5	5
CSNK1A1	0.023	0.004	-10000	0	-10000	0	0
IFT172	0.022	0.004	-10000	0	-10000	0	0
RBBP7	0.023	0.003	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.019	0.042	-10000	0	-0.17	2	2
GNAZ	0.01	0.065	-10000	0	-0.35	17	17
RBBP4	0.02	0.028	-10000	0	-0.35	3	3
CSNK1G1	0.022	0.005	-10000	0	-10000	0	0
PIAS1	0.022	0.005	-10000	0	-10000	0	0
PRKACA	0.022	0.005	-10000	0	-10000	0	0
GLI2/SPOP	-0.027	0.1	-10000	0	-0.33	25	25
STK36	0.021	0.012	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.044	0.1	-10000	0	-0.34	28	28
PTCH1	-0.086	0.19	-10000	0	-0.56	46	46
MIM/GLI1	-0.088	0.22	-10000	0	-0.53	85	85
CREBBP	-0.03	0.12	-10000	0	-0.31	88	88
Su(fu)/SIN3/HDAC complex	0.007	0.083	0.19	1	-0.42	13	14

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.073	0.15	0.48	4	-0.76	3	7
CRP	0.089	0.18	0.51	22	-0.69	4	26
cell cycle arrest	0.066	0.16	0.47	6	-0.72	6	12
TIMP1	0.064	0.15	0.44	5	-0.62	7	12
IL6ST	-0.027	0.13	-10000	0	-0.34	79	79
Rac1/GDP	0.021	0.12	0.28	5	-0.34	29	34
AP1	0.014	0.14	-10000	0	-0.53	12	12
GAB2	0.021	0.032	-10000	0	-0.35	4	4
TNFSF11	0.077	0.16	0.47	3	-0.69	4	7
HSP90B1	0.044	0.092	-10000	0	-0.65	6	6
GAB1	0.02	0.032	-10000	0	-0.35	4	4
MAPK14	-0.005	0.12	-10000	0	-0.38	25	25
AKT1	0.026	0.06	-10000	0	-0.44	4	4
FOXO1	0.026	0.06	0.32	1	-0.45	3	4
MAP2K6	-0.007	0.11	0.22	6	-0.37	29	35
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	0.034	0.12	0.31	9	-0.36	20	29
MITF	-0.015	0.13	0.23	6	-0.36	44	50
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.021	0.007	-10000	0	-10000	0	0
A2M	0.002	0.15	-10000	0	-1.1	9	9
CEBPB	0.026	0.008	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.022	0.11	-10000	0	-0.52	11	11
STAT3	0.062	0.17	0.47	6	-0.77	6	12
STAT1	0.024	0.059	-10000	0	-0.82	2	2
CEBPD	0.074	0.16	0.46	7	-0.77	4	11
PIK3CA	0.021	0.018	-10000	0	-0.35	1	1
PI3K	0.028	0.029	-10000	0	-0.24	5	5
JUN	0.018	0.042	-10000	0	-0.35	7	7
PIAS3/MITF	-0.014	0.13	0.27	1	-0.35	43	44
MAPK11	-0.005	0.11	0.24	1	-0.38	24	25
STAT3 (dimer)/FOXO1	0.065	0.15	0.41	10	-0.52	9	19
GRB2/SOS1/GAB family	0.024	0.12	-10000	0	-0.35	26	26
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.01	0.11	0.21	5	-0.35	30	35
GRB2	0.022	0.006	-10000	0	-10000	0	0
JAK2	0.016	0.048	-10000	0	-0.35	9	9
LBP	0.084	0.17	0.48	16	-0.63	6	22
PIK3R1	0.019	0.036	-10000	0	-0.35	5	5
JAK1	0.025	0.018	-10000	0	-0.34	1	1
MYC	0.078	0.2	0.5	6	-0.9	10	16
FGG	0.062	0.15	0.5	4	-0.76	3	7
macrophage differentiation	0.066	0.16	0.47	6	-0.72	6	12
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.01	0.12	0.23	5	-0.25	64	69
JUNB	0.062	0.17	0.49	1	-0.83	8	9
FOS	-0.088	0.17	-10000	0	-0.35	160	160
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.002	0.12	0.26	4	-0.37	31	35
STAT1/PIAS1	0.033	0.12	0.31	5	-0.34	22	27
GRB2/SOS1/GAB family/SHP2/PI3K	0.029	0.06	-10000	0	-0.43	5	5
STAT3 (dimer)	0.064	0.17	0.47	6	-0.75	6	12
PRKCD	0.049	0.14	0.37	14	-0.5	7	21
IL6R	-0.006	0.096	-10000	0	-0.35	39	39
SOCS3	-0.012	0.13	-10000	0	-0.71	6	6
gp130 (dimer)/JAK1/JAK1/LMO4	0.02	0.093	-10000	0	-0.2	78	78
Rac1/GTP	0.026	0.12	0.28	6	-0.36	24	30
HCK	0.025	0.03	0.28	7	-10000	0	7
MAPKKK cascade	0.037	0.11	-10000	0	-0.55	11	11
bone resorption	0.077	0.16	0.45	6	-0.65	4	10
IRF1	0.061	0.15	0.56	2	-0.76	3	5
mol:GDP	0.004	0.11	0.24	7	-0.36	28	35
SOS1	0.023	0.004	-10000	0	-10000	0	0
VAV1	0	0.11	0.24	7	-0.36	28	35
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.021	0.15	-10000	0	-0.47	40	40
PTPN11	0.022	0.064	-10000	0	-0.66	4	4
IL6/IL6RA	0.008	0.09	0.22	6	-0.26	49	55
gp130 (dimer)/TYK2/TYK2/LMO4	0.014	0.089	-10000	0	-0.2	75	75
gp130 (dimer)/JAK2/JAK2/LMO4	0.011	0.096	-10000	0	-0.2	85	85
IL6	0.023	0.071	0.29	9	-0.35	14	23
PIAS3	0.019	0.009	-10000	0	-10000	0	0
PTPRE	0	0.03	0.26	1	-0.35	1	2
PIAS1	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.023	0.005	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.02	0.11	0.2	2	-0.28	64	66
LMO4	0.029	0.012	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	0.036	0.15	0.42	1	-0.66	8	9
MCL1	0.059	0.1	0.39	4	-0.52	1	5

×

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	-0.01	0.014	0.3	1	-10000	0	1
BAD/BCL-XL/YWHAZ	0.03	0.017	0.21	1	-10000	0	1
CDKN1B	0.002	0.047	0.19	1	-0.29	7	8
CDKN1A	0.009	0.046	0.19	8	-0.29	8	16
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.021	0.007	-10000	0	-10000	0	0
FOXO3	0.008	0.037	0.19	2	-0.28	6	8
AKT1	0.007	0.036	-10000	0	-0.3	7	7
BAD	0.022	0.004	-10000	0	-10000	0	0
AKT3	-0.068	0.12	-10000	0	-0.26	155	155
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.006	0.042	0.19	1	-0.29	8	9
AKT1/ASK1	0.029	0.051	0.23	3	-0.28	8	11
BAD/YWHAZ	0.039	0.018	-10000	0	-10000	0	0
RICTOR	0.021	0.023	-10000	0	-0.35	2	2
RAF1	0.022	0.004	-10000	0	-10000	0	0
JNK cascade	-0.026	0.047	0.27	8	-10000	0	8
TSC1	0.009	0.024	-10000	0	-0.27	2	2
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
AKT1/RAF1	0.032	0.051	0.24	2	-0.28	7	9
EP300	0.021	0.006	-10000	0	-10000	0	0
mol:GDP	0.009	0.04	-10000	0	-0.29	8	8
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.007	0.038	0.19	1	-0.29	7	8
YWHAQ	0.022	0.005	-10000	0	-10000	0	0
TBC1D4	0.001	0.012	-10000	0	-0.19	2	2
MAP3K5	0.022	0.016	-10000	0	-0.35	1	1
MAPKAP1	0.022	0.005	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.046	0.079	0.37	8	-0.24	14	22
YWHAH	0.022	0.006	-10000	0	-10000	0	0
AKT1S1	0.007	0.042	-10000	0	-0.29	8	8
CASP9	0.009	0.035	0.19	3	-0.28	5	8
YWHAB	0.022	0.005	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.023	0.067	0.28	7	-0.28	8	15
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.042	0.015	-10000	0	-10000	0	0
YWHAE	0.021	0.007	-10000	0	-10000	0	0
SRC	0.022	0.005	-10000	0	-10000	0	0
AKT2/p21CIP1	0.014	0.047	0.2	11	-0.26	7	18
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.005	0.047	-10000	0	-0.28	13	13
CHUK	0.009	0.04	-10000	0	-0.28	6	6
BAD/BCL-XL	0.03	0.043	0.26	1	-0.28	5	6
mTORC2	0.026	0.016	-10000	0	-0.18	2	2
AKT2	0.01	0.003	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.054	0.09	0.27	15	-0.37	10	25
PDPK1	0.022	0.005	-10000	0	-10000	0	0
MDM2	0.008	0.04	0.19	3	-0.29	7	10
MAPKKK cascade	-0.032	0.05	0.28	7	-0.24	2	9
MDM2/Cbp/p300	0.039	0.055	0.28	2	-0.27	7	9
TSC1/TSC2	0.007	0.039	0.26	4	-0.26	5	9
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.053	0.27	2	-0.25	8	10
glucose import	-0.08	0.091	0.2	5	-0.18	242	247
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.008	0.037	0.18	3	-0.18	11	14
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.082	0.09	0.2	2	-0.18	242	244
GSK3A	0.008	0.043	0.19	5	-0.29	8	13
FOXO1	0.007	0.036	-10000	0	-0.29	6	6
GSK3B	0.008	0.043	0.19	4	-0.29	8	12
SFN	0.21	0.12	0.28	385	-10000	0	385
G1/S transition of mitotic cell cycle	0.015	0.058	0.24	11	-0.28	8	19
p27Kip1/14-3-3 family	0.054	0.083	0.28	4	-0.51	6	10
PRKACA	0.022	0.005	-10000	0	-10000	0	0
KPNA1	0.022	0.004	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
RHEB	0.022	0.005	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.023	0.004	-10000	0	-10000	0	0
HDAC3	0.023	0.003	-10000	0	-10000	0	0
VDR	0.029	0.042	0.29	13	-10000	0	13
Cbp/p300/PCAF	0.038	0.033	-10000	0	-0.2	8	8
EP300	0.021	0.006	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.002	0.075	0.16	2	-0.28	25	27
KAT2B	0.017	0.045	-10000	0	-0.35	8	8
MAPK14	0.023	0.004	-10000	0	-10000	0	0
AKT1	0.004	0.07	0.18	21	-0.22	19	40
RAR alpha/9cRA/Cyclin H	0.016	0.095	0.22	1	-0.26	39	40
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.003	0.087	0.16	1	-0.28	34	35
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.004	0.079	-10000	0	-0.21	50	50
NCOR2	0.023	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.023	0.19	9	-10000	0	9
RXRs/RARs/NRIP1/9cRA	-0.011	0.15	0.28	3	-0.43	47	50
NCOA2	0.009	0.065	-10000	0	-0.35	17	17
NCOA3	0.022	0.015	0.33	1	-10000	0	1
NCOA1	0.022	0.017	-10000	0	-0.35	1	1
VDR/VDR/DNA	0.029	0.042	0.29	13	-10000	0	13
RARG	0.023	0.004	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.029	0.008	-10000	0	-10000	0	0
MAPK3	0.022	0.006	-10000	0	-10000	0	0
MAPK1	0.022	0.005	-10000	0	-10000	0	0
MAPK8	0.019	0.036	-10000	0	-0.35	5	5
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.007	0.13	0.27	4	-0.37	40	44
RARA	0.006	0.066	0.18	5	-0.22	33	38
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.009	0.089	0.16	1	-0.27	38	39
PRKCA	0.001	0.087	-10000	0	-0.35	31	31
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.011	0.16	0.26	1	-0.43	46	47
RXRG	-0.016	0.12	0.23	11	-0.27	80	91
RXRA	0.004	0.061	0.18	6	-0.2	34	40
RXRB	0.009	0.081	0.22	5	-0.26	35	40
VDR/Vit D3/DNA	0.019	0.023	0.19	9	-10000	0	9
RBP1	0.008	0.072	-10000	0	-0.35	21	21
CRBP1/9-cic-RA	0.007	0.05	-10000	0	-0.24	21	21
RARB	0.017	0.048	-10000	0	-0.35	9	9
PRKCG	0.05	0.095	0.28	65	-0.35	6	71
MNAT1	0.022	0.004	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.014	0.14	0.27	3	-0.42	42	45
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.004	0.13	0.25	4	-0.36	49	53
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.11	0.21	8	-0.32	37	45
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.012	0.16	0.26	2	-0.43	46	48
positive regulation of DNA binding	0.007	0.086	-10000	0	-0.25	39	39
NRIP1	-0.013	0.16	-10000	0	-0.66	17	17
RXRs/RARs	-0.009	0.16	0.26	1	-0.42	47	48
RXRs/RXRs/DNA/9cRA	-0.018	0.12	0.2	3	-0.37	43	46
PRKACA	0.022	0.005	-10000	0	-10000	0	0
CDK7	0.022	0.005	-10000	0	-10000	0	0
TFIIH	0.044	0.012	-10000	0	-10000	0	0
RAR alpha/9cRA	0.029	0.075	-10000	0	-0.25	17	17
CCNH	0.022	0.005	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.04	0.017	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.029	0.009	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.054	0.085	0.28	66	-10000	0	66
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.02	0.017	-10000	0	-0.35	1	1
RAC1-CDC42/GTP/PAK family	-0.014	0.062	-10000	0	-0.17	70	70
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.022	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	0.022	0.005	-10000	0	-10000	0	0
FYN	0.023	0.004	-10000	0	-10000	0	0
MAP3K12	0.02	0.032	-10000	0	-0.35	4	4
FGR	0.016	0.051	-10000	0	-0.35	10	10
p38 alpha/TAB1	-0.022	0.073	-10000	0	-0.31	22	22
PRKG1	-0.14	0.18	-10000	0	-0.35	226	226
DUSP8	0.019	0.036	-10000	0	-0.35	5	5
PGK/cGMP/p38 alpha	-0.046	0.11	-10000	0	-0.3	41	41
apoptosis	-0.021	0.069	-10000	0	-0.29	23	23
RAL/GTP	0.03	0.006	-10000	0	-10000	0	0
LYN	0.021	0.007	-10000	0	-10000	0	0
DUSP1	-0.062	0.16	-10000	0	-0.35	122	122
PAK1	0.022	0.004	-10000	0	-10000	0	0
SRC	0.022	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.051	0.021	-10000	0	-10000	0	0
TRAF6	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.005	-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	0.023	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.029	0.008	-10000	0	-10000	0	0
MAPK11	0.021	0.097	0.25	13	-0.38	13	26
BLK	0.037	0.068	0.28	38	-10000	0	38
HCK	0.025	0.03	0.28	7	-10000	0	7
MAP2K3	0.021	0.006	-10000	0	-10000	0	0
DUSP16	0.023	0.003	-10000	0	-10000	0	0
DUSP10	0.02	0.008	-10000	0	-10000	0	0
TRAF6/MEKK3	0.027	0.009	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.019	0.1	0.22	16	-0.36	18	34
positive regulation of innate immune response	0.024	0.11	0.28	14	-0.45	14	28
LCK	0.024	0.028	0.28	4	-0.35	1	5
p38alpha-beta/MKP7	0.032	0.11	0.28	12	-0.43	14	26
p38alpha-beta/MKP5	0.023	0.11	0.3	9	-0.43	14	23
PGK/cGMP	-0.092	0.13	-10000	0	-0.24	226	226
PAK2	0.021	0.007	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.009	0.12	0.29	9	-0.39	24	33
CDC42	0.022	0.005	-10000	0	-10000	0	0
RALB	0.023	0.003	-10000	0	-10000	0	0
RALA	0.023	0.004	-10000	0	-10000	0	0
PAK3	-0.034	0.13	-10000	0	-0.35	80	80

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.009	0.12	0.31	11	-0.32	34	45
IKBKB	0.021	0.087	0.27	12	-0.3	9	21
AKT1	0.014	0.098	0.27	32	-0.22	16	48
IKBKG	0.019	0.081	0.25	4	-0.33	6	10
CALM1	0.012	0.097	0.23	7	-0.35	10	17
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
MAP3K1	0.002	0.16	0.33	10	-0.45	41	51
MAP3K7	0.023	0.003	-10000	0	-10000	0	0
mol:Ca2+	0.015	0.099	0.23	5	-0.37	10	15
DOK1	0.023	0.003	-10000	0	-10000	0	0
AP-1	-0.006	0.089	0.26	8	-0.23	17	25
LYN	0.021	0.007	-10000	0	-10000	0	0
BLNK	0.021	0.026	0.28	1	-0.35	2	3
SHC1	0.019	0.009	-10000	0	-10000	0	0
BCR complex	0.034	0.085	0.21	51	-0.26	25	76
CD22	-0.024	0.12	0.23	4	-0.45	28	32
CAMK2G	0.017	0.098	0.26	16	-0.37	6	22
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
INPP5D	0.022	0.016	-10000	0	-0.35	1	1
SHC/GRB2/SOS1	0.018	0.041	-10000	0	-0.18	12	12
GO:0007205	0.014	0.1	0.23	5	-0.36	11	16
SYK	0.022	0.012	0.28	1	-10000	0	1
ELK1	0.012	0.1	0.25	8	-0.35	11	19
NFATC1	0.004	0.13	0.26	15	-0.37	30	45
B-cell antigen/BCR complex	0.034	0.085	0.21	51	-0.26	25	76
PAG1/CSK	0.029	0.02	-10000	0	-0.25	2	2
NFKBIB	0.022	0.046	0.15	9	-0.13	19	28
HRAS	0.016	0.094	0.25	10	-0.32	14	24
NFKBIA	0.022	0.045	0.16	8	-0.12	17	25
NF-kappa-B/RelA/I kappa B beta	0.025	0.04	0.15	9	-0.13	1	10
RasGAP/Csk	0.05	0.077	0.29	2	-0.19	25	27
mol:GDP	0.012	0.1	0.23	3	-0.35	12	15
PTEN	0.021	0.006	-10000	0	-10000	0	0
CD79B	0.005	0.077	-10000	0	-0.35	24	24
NF-kappa-B/RelA/I kappa B alpha	0.025	0.039	0.15	9	-0.13	1	10
GRB2	0.022	0.006	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.011	0.16	0.38	6	-0.45	36	42
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
mol:IP3	0.018	0.096	0.23	5	-0.39	9	14
CSK	0.022	0.005	-10000	0	-10000	0	0
FOS	-0.032	0.12	0.28	6	-0.33	26	32
CHUK	0.013	0.098	0.25	6	-0.36	18	24
IBTK	0.023	0.003	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.029	0.093	0.26	2	-0.33	8	10
PTPN6	-0.027	0.11	0.22	4	-0.44	26	30
RELA	0.022	0.004	-10000	0	-10000	0	0
BCL2A1	0.02	0.028	0.12	4	-10000	0	4
VAV2	0.009	0.12	0.46	1	-0.43	24	25
ubiquitin-dependent protein catabolic process	0.023	0.045	0.15	9	-0.12	21	30
BTK	0.007	0.12	-10000	0	-0.94	8	8
CD19	-0.003	0.094	0.2	4	-0.4	23	27
MAP4K1	0.028	0.04	0.29	12	-10000	0	12
CD72	0.024	0.02	0.28	3	-10000	0	3
PAG1	0.02	0.024	-10000	0	-0.35	2	2
MAPK14	0.007	0.14	0.3	12	-0.39	38	50
SH3BP5	-0.03	0.13	-10000	0	-0.35	76	76
PIK3AP1	0.02	0.099	0.26	9	-0.35	10	19
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.015	0.091	0.24	1	-0.49	9	10
RAF1	0.014	0.092	0.24	12	-0.31	13	25
RasGAP/p62DOK/SHIP	0.048	0.074	0.32	1	-0.19	26	27
CD79A	0.045	0.084	0.28	53	-0.35	4	57
re-entry into mitotic cell cycle	-0.006	0.088	0.25	9	-0.23	17	26
RASA1	0.019	0.036	-10000	0	-0.35	5	5
MAPK3	0.013	0.082	0.25	11	-0.28	8	19
MAPK1	0.011	0.079	0.24	8	-0.28	8	16
CD72/SHP1	0.004	0.14	0.3	9	-0.42	26	35
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
MAPK8	0.004	0.15	0.36	11	-0.38	41	52
actin cytoskeleton organization	0.01	0.12	0.32	9	-0.37	27	36
NF-kappa-B/RelA	0.051	0.078	0.27	10	-0.2	6	16
Calcineurin	0.026	0.088	0.24	1	-0.33	7	8
PI3K	-0.02	0.095	-10000	0	-0.36	23	23
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.024	0.1	0.25	8	-0.34	15	23
SOS1	0.023	0.003	-10000	0	-10000	0	0
Bam32/HPK1	-0.013	0.22	-10000	0	-0.62	53	53
DAPP1	-0.035	0.24	-10000	0	-0.71	52	52
cytokine secretion	0.005	0.12	0.26	15	-0.35	30	45
mol:DAG	0.018	0.096	0.23	5	-0.39	9	14
PLCG2	0.02	0.021	0.28	1	-0.35	1	2
MAP2K1	0.013	0.084	0.24	9	-0.29	10	19
B-cell antigen/BCR complex/FcgammaRIIB	0.04	0.075	0.21	47	-0.22	20	67
mol:PI-3-4-5-P3	-0.014	0.084	0.21	7	-0.28	18	25
ETS1	0.014	0.094	0.26	16	-0.34	6	22
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.058	0.073	0.29	2	-0.19	19	21
B-cell antigen/BCR complex/LYN	0.001	0.097	0.22	2	-0.4	24	26
MALT1	0.022	0.005	-10000	0	-10000	0	0
TRAF6	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.008	0.12	0.35	4	-0.4	24	28
B-cell antigen/BCR complex/LYN/SYK	0.008	0.13	0.35	4	-0.41	26	30
CARD11	0.014	0.1	0.26	10	-0.35	12	22
FCGR2B	0.018	0.027	0.28	1	-0.35	2	3
PPP3CA	0.022	0.004	-10000	0	-10000	0	0
BCL10	0.023	0.002	-10000	0	-10000	0	0
IKK complex	0.021	0.055	0.18	28	-0.13	10	38
PTPRC	0.015	0.047	0.28	1	-0.35	8	9
PDPK1	0.002	0.083	0.24	25	-0.21	14	39
PPP3CB	0.022	0.005	-10000	0	-10000	0	0
PPP3CC	0.017	0.033	-10000	0	-0.35	4	4
POU2F2	0.02	0.031	0.14	9	-10000	0	9

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.012	0.019	-10000	0	-10000	0	0
HSPA8	0.023	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.002	0.092	-10000	0	-0.23	57	57
AKT1	0.024	0.006	-10000	0	-10000	0	0
GSC	0.055	0.1	0.47	2	-0.45	3	5
NKX2-5	-0.005	0.018	-10000	0	-0.12	1	1
muscle cell differentiation	-0.015	0.11	0.43	10	-10000	0	10
SMAD2-3/SMAD4/SP1	0.059	0.061	-10000	0	-0.25	4	4
SMAD4	0.013	0.038	-10000	0	-10000	0	0
CBFB	0.02	0.008	-10000	0	-10000	0	0
SAP18	0.022	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.038	0.04	0.2	13	-0.21	3	16
SMAD3/SMAD4/VDR	0.051	0.052	0.24	2	-0.18	1	3
MYC	0.012	0.046	-10000	0	-0.35	8	8
CDKN2B	-0.008	0.1	-10000	0	-0.53	10	10
AP1	-0.027	0.11	-10000	0	-0.3	22	22
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.019	0.072	-10000	0	-0.45	8	8
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.027	0.048	0.18	3	-0.24	4	7
SP3	0.024	0.003	-10000	0	-10000	0	0
CREB1	0.023	0.003	-10000	0	-10000	0	0
FOXH1	0.088	0.12	0.29	134	-10000	0	134
SMAD3/SMAD4/GR	-0.008	0.1	-10000	0	-0.23	77	77
GATA3	0.028	0.057	0.28	13	-0.35	6	19
SKI/SIN3/HDAC complex/NCoR1	0.008	0.075	-10000	0	-0.38	13	13
MEF2C/TIF2	0.008	0.11	0.28	6	-0.34	41	47
endothelial cell migration	-0.014	0.12	0.92	7	-10000	0	7
MAX	0.022	0.005	-10000	0	-10000	0	0
RBBP7	0.023	0.003	-10000	0	-10000	0	0
RBBP4	0.021	0.028	-10000	0	-0.35	3	3
RUNX2	0.029	0.045	0.28	15	-0.35	1	16
RUNX3	0.029	0.041	0.28	14	-10000	0	14
RUNX1	0.023	0.003	-10000	0	-10000	0	0
CTBP1	0.022	0.005	-10000	0	-10000	0	0
NR3C1	-0.031	0.13	-10000	0	-0.35	77	77
VDR	0.029	0.042	0.29	13	-10000	0	13
CDKN1A	0.008	0.063	-10000	0	-0.84	2	2
KAT2B	0.016	0.046	-10000	0	-0.35	8	8
SMAD2/SMAD2/SMAD4/FOXH1	0.087	0.1	0.25	82	-10000	0	82
DCP1A	0.022	0.005	-10000	0	-10000	0	0
SKI	0.023	0.004	-10000	0	-10000	0	0
SERPINE1	0.014	0.12	-10000	0	-0.93	7	7
SMAD3/SMAD4/ATF2	0.028	0.058	-10000	0	-0.29	5	5
SMAD3/SMAD4/ATF3	0.007	0.083	-10000	0	-0.24	41	41
SAP30	0.023	0.004	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.022	0.03	-10000	0	-10000	0	0
JUN	-0.037	0.1	-10000	0	-0.32	18	18
SMAD3/SMAD4/IRF7	0.033	0.062	0.3	6	-0.25	3	9
TFE3	0.024	0.01	-10000	0	-10000	0	0
COL1A2	0.02	0.074	-10000	0	-0.54	7	7
mesenchymal cell differentiation	-0.032	0.061	0.24	4	-0.24	12	16
DLX1	0.05	0.082	0.28	60	-10000	0	60
TCF3	0.021	0.006	-10000	0	-10000	0	0
FOS	-0.088	0.17	-10000	0	-0.36	160	160
SMAD3/SMAD4/Max	0.028	0.052	-10000	0	-0.25	3	3
Cbp/p300/SNIP1	0.04	0.016	-10000	0	-10000	0	0
ZBTB17	0.02	0.009	-10000	0	-10000	0	0
LAMC1	0.007	0.043	0.2	8	-0.22	3	11
TGIF2/HDAC complex/SMAD3/SMAD4	0.028	0.052	-10000	0	-0.25	3	3
IRF7	0.028	0.037	0.29	10	-10000	0	10
ESR1	-0.017	0.11	-10000	0	-0.35	55	55
HNF4A	0.058	0.092	0.28	76	-10000	0	76
MEF2C	0.009	0.12	0.22	35	-0.35	41	76
SMAD2-3/SMAD4	0.033	0.062	-10000	0	-0.27	3	3
Cbp/p300/Src-1	0.037	0.02	-10000	0	-0.19	1	1
IGHV3OR16-13	0.005	0.034	-10000	0	-0.34	5	5
TGIF2/HDAC complex	0.022	0.005	-10000	0	-10000	0	0
CREBBP	0.014	0.017	-10000	0	-10000	0	0
SKIL	0.021	0.007	-10000	0	-10000	0	0
HDAC1	0.023	0.004	-10000	0	-10000	0	0
HDAC2	0.023	0.003	-10000	0	-10000	0	0
SNIP1	0.023	0.004	-10000	0	-10000	0	0
GCN5L2	-0.002	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.033	0.054	-10000	0	-0.25	3	3
MSG1/HSC70	0.038	0.038	0.21	16	-0.25	3	19
SMAD2	0.022	0.027	-10000	0	-10000	0	0
SMAD3	0.009	0.046	-10000	0	-0.37	4	4
SMAD3/E2F4-5/DP1/p107/SMAD4	0.013	0.031	-10000	0	-0.21	5	5
SMAD2/SMAD2/SMAD4	0.001	0.057	0.18	4	-0.24	14	18
NCOR1	0.021	0.007	-10000	0	-10000	0	0
NCOA2	0.009	0.065	-10000	0	-0.35	17	17
NCOA1	0.022	0.017	-10000	0	-0.35	1	1
MYOD/E2A	0.04	0.046	0.21	35	-10000	0	35
SMAD2-3/SMAD4/SP1/MIZ-1	0.067	0.062	-10000	0	-0.27	2	2
IFNB1	0.004	0.048	0.24	10	-0.23	2	12
SMAD3/SMAD4/MEF2C	0.026	0.12	0.24	7	-0.36	39	46
CITED1	0.029	0.053	0.28	17	-0.35	3	20
SMAD2-3/SMAD4/ARC105	0.043	0.062	-10000	0	-0.24	3	3
RBL1	0.022	0.005	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.016	0.047	0.22	1	-0.34	3	4
RUNX1-3/PEBPB2	0.044	0.028	0.2	11	-10000	0	11
SMAD7	-0.025	0.12	-10000	0	-0.44	14	14
MYC/MIZ-1	0.02	0.037	-10000	0	-0.25	8	8
SMAD3/SMAD4	-0.011	0.068	-10000	0	-0.38	8	8
IL10	0.015	0.069	0.24	24	-0.22	5	29
PIASy/HDAC complex	0.023	0.008	-10000	0	-10000	0	0
PIAS3	0.018	0.009	-10000	0	-10000	0	0
CDK2	0.018	0.012	-10000	0	-10000	0	0
IL5	0.005	0.05	0.2	7	-0.21	8	15
CDK4	0.014	0.017	-10000	0	-10000	0	0
PIAS4	0.023	0.008	-10000	0	-10000	0	0
ATF3	-0.008	0.097	-10000	0	-0.35	40	40
SMAD3/SMAD4/SP1	0.035	0.057	-10000	0	-0.24	5	5
FOXG1	0.14	0.13	0.28	254	-10000	0	254
FOXO3	0.009	0.007	-10000	0	-10000	0	0
FOXO1	0.007	0.017	-10000	0	-0.24	2	2
FOXO4	0.007	0.017	-10000	0	-0.24	2	2
heart looping	0.009	0.12	0.22	35	-0.35	41	76
CEBPB	0.023	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.044	0.074	0.23	35	-0.24	3	38
MYOD1	0.041	0.075	0.28	47	-10000	0	47
SMAD3/SMAD4/HNF4	0.049	0.079	0.22	48	-0.24	3	51
SMAD3/SMAD4/GATA3	0.037	0.07	0.25	4	-0.23	9	13
SnoN/SIN3/HDAC complex/NCoR1	0.021	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.058	0.052	0.27	2	-0.21	3	5
SMAD3/SMAD4/SP1-3	0.058	0.049	-10000	0	-0.21	5	5
MED15	0.022	0.005	-10000	0	-10000	0	0
SP1	0.025	0.016	-10000	0	-0.14	2	2
SIN3B	0.022	0.006	-10000	0	-10000	0	0
SIN3A	0.022	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.078	0.11	0.24	78	-0.2	36	114
ITGB5	0.007	0.044	0.32	1	-0.22	2	3
TGIF/SIN3/HDAC complex/CtBP	0.016	0.054	-10000	0	-0.36	6	6
SMAD3/SMAD4/AR	-0.013	0.11	-10000	0	-0.22	91	91
AR	-0.04	0.14	-10000	0	-0.35	90	90
negative regulation of cell growth	0.006	0.069	-10000	0	-0.3	9	9
SMAD3/SMAD4/MYOD	0.038	0.071	0.23	29	-0.25	3	32
E2F5	0.021	0.007	-10000	0	-10000	0	0
E2F4	0.02	0.008	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.091	0.093	0.27	42	-10000	0	42
SMAD2-3/SMAD4/FOXO1-3a-4	0.015	0.039	-10000	0	-0.27	3	3
TFDP1	0.022	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.012	0.12	-10000	0	-0.32	18	18
SMAD3/SMAD4/RUNX2	0.033	0.061	0.24	12	-0.24	4	16
TGIF2	0.022	0.005	-10000	0	-10000	0	0
TGIF1	0.022	0.005	-10000	0	-10000	0	0
ATF2	0.021	0.028	-10000	0	-0.35	3	3

×

EPO signaling pathway

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
BCL2L1	0	0.11	-10000	0	-0.41	8	8
CRKL	-0.01	0.068	0.2	14	-0.24	5	19
mol:DAG	0.003	0.066	0.19	1	-0.25	17	18
HRAS	0.013	0.094	0.28	21	-0.23	5	26
MAPK8	0	0.073	0.18	60	-0.19	19	79
RAP1A	-0.01	0.07	0.2	14	-0.24	5	19
GAB1	-0.012	0.071	0.2	12	-0.25	7	19
MAPK14	0.002	0.07	0.18	60	-0.18	14	74
EPO	0.008	0.067	0.29	1	-0.35	16	17
PLCG1	0.003	0.067	0.19	1	-0.25	17	18
EPOR/TRPC2/IP3 Receptors	0.021	0.037	0.29	7	-10000	0	7
RAPGEF1	0.022	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.031	0.055	0.21	8	-0.2	18	26
GAB1/SHC/GRB2/SOS1	0.019	0.06	0.26	1	-0.23	5	6
EPO/EPOR (dimer)	0.021	0.057	0.22	7	-0.25	16	23
IRS2	-0.031	0.083	0.19	13	-0.26	15	28
STAT1	-0.001	0.087	-10000	0	-0.28	21	21
STAT5B	0	0.079	-10000	0	-0.26	23	23
cell proliferation	0.003	0.081	0.2	66	-0.2	5	71
GAB1/SHIP/PIK3R1/SHP2/SHC	0.012	0.06	-10000	0	-0.24	9	9
TEC	-0.011	0.068	0.22	11	-0.24	5	16
SOCS3	0.021	0.023	-10000	0	-0.35	2	2
STAT1 (dimer)	-0.001	0.087	0.28	1	-0.27	21	22
JAK2	0.013	0.051	-10000	0	-0.35	9	9
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
EPO/EPOR (dimer)/JAK2	0.038	0.072	-10000	0	-0.19	23	23
EPO/EPOR	0.021	0.057	0.22	7	-0.25	16	23
LYN	0.017	0.015	-10000	0	-10000	0	0
TEC/VAV2	0.014	0.065	0.27	3	-0.24	5	8
elevation of cytosolic calcium ion concentration	0.021	0.037	0.29	7	-10000	0	7
SHC1	0.019	0.009	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.03	0.054	0.21	6	-0.2	15	21
mol:IP3	0.003	0.066	0.19	1	-0.25	17	18
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.001	0.095	0.28	4	-0.27	18	22
SH2B3	0.019	0.024	-10000	0	-0.35	1	1
NFKB1	0.001	0.071	0.19	38	-0.18	16	54
EPO/EPOR (dimer)/JAK2/SOCS3	0.001	0.053	0.2	1	-0.21	27	28
PTPN6	-0.009	0.066	0.16	33	-0.23	7	40
TEC/VAV2/GRB2	0.022	0.064	0.27	2	-0.24	5	7
EPOR	0.021	0.037	0.29	7	-10000	0	7
INPP5D	0.022	0.016	-10000	0	-0.35	1	1
mol:GDP	0.018	0.061	0.26	1	-0.24	5	6
SOS1	0.023	0.003	-10000	0	-10000	0	0
PLCG2	0.02	0.021	0.28	1	-0.35	1	2
CRKL/CBL/C3G	0.023	0.066	0.27	3	-0.23	5	8
VAV2	-0.011	0.067	0.21	13	-0.24	5	18
CBL	-0.01	0.069	0.22	10	-0.24	5	15
SHC/Grb2/SOS1	0.013	0.052	-10000	0	-0.24	4	4
STAT5A	0	0.078	-10000	0	-0.26	22	22
GRB2	0.022	0.006	-10000	0	-10000	0	0
STAT5 (dimer)	0.004	0.1	-10000	0	-0.32	34	34
LYN/PLCgamma2	0.025	0.023	0.21	1	-0.24	1	2
PTPN11	0.023	0.003	-10000	0	-10000	0	0
BTK	-0.01	0.072	0.32	4	-0.28	5	9
BCL2	-0.04	0.23	-10000	0	-0.74	50	50

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.065	0.059	-10000	0	-0.17	10	10
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.022	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.037	0.039	0.27	2	-10000	0	2
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.042	0.038	-10000	0	-0.21	10	10
antigen processing and presentation of peptide antigen via MHC class I	-0.032	0.055	-10000	0	-0.21	6	6
CaM/Ca2+	0.063	0.053	-10000	0	-0.17	7	7
RAP1A	0.023	0.002	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.026	0.036	0.17	4	-0.17	8	12
AKT1	0.008	0.072	0.27	14	-0.28	1	15
MAP2K1	-0.01	0.039	0.19	9	-10000	0	9
MAP3K11	-0.005	0.043	0.21	7	-0.17	2	9
IFNGR1	0.023	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.15	0.18	0.26	1	-0.31	275	276
Rap1/GTP	-0.019	0.024	-10000	0	-10000	0	0
CRKL/C3G	0.031	0.01	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.074	0.061	-10000	0	-0.18	10	10
CEBPB	-0.006	0.13	0.31	7	-0.54	21	28
STAT3	0.022	0.006	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.051	0.15	-10000	0	-0.68	19	19
STAT1	-0.006	0.045	0.19	11	-10000	0	11
CALM1	0.022	0.004	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.045	0.088	0.29	60	-10000	0	60
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
STAT1 (dimer)/PIAS1	0.018	0.044	0.27	3	-10000	0	3
CEBPB/PTGES2/Cbp/p300	0.011	0.08	-10000	0	-0.37	16	16
mol:Ca2+	0.062	0.056	-10000	0	-0.17	10	10
MAPK3	-0.016	0.14	-10000	0	-0.64	22	22
STAT1 (dimer)	-0.037	0.075	-10000	0	-0.28	6	6
MAPK1	-0.029	0.17	-10000	0	-0.68	32	32
JAK2	0.017	0.049	-10000	0	-0.35	9	9
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
JAK1	0.023	0.018	-10000	0	-0.35	1	1
CAMK2D	0.022	0.017	-10000	0	-0.35	1	1
DAPK1	0.001	0.087	0.3	4	-0.38	15	19
SMAD7	-0.011	0.05	0.17	13	-0.2	3	16
CBL/CRKL/C3G	0.032	0.04	0.27	3	-10000	0	3
PI3K	0.052	0.053	-10000	0	-0.2	4	4
IFNG	0.045	0.088	0.29	60	-10000	0	60
apoptosis	0.001	0.075	0.26	2	-0.31	15	17
CAMK2G	0.022	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	0.022	0.006	-10000	0	-10000	0	0
CAMK2A	-0.18	0.18	-10000	0	-0.35	292	292
CAMK2B	0.064	0.097	0.28	86	-0.35	1	87
FRAP1	0.006	0.067	0.23	20	-0.26	1	21
PRKCD	0.007	0.074	0.24	20	-0.29	1	21
RAP1B	0.023	0.002	-10000	0	-10000	0	0
negative regulation of cell growth	-0.032	0.055	-10000	0	-0.21	6	6
PTPN2	0.022	0.004	-10000	0	-10000	0	0
EP300	0.022	0.006	-10000	0	-10000	0	0
IRF1	-0.004	0.046	0.28	5	-0.31	1	6
STAT1 (dimer)/PIASy	0.016	0.043	0.27	3	-10000	0	3
SOCS1	-0.014	0.19	-10000	0	-1	19	19
mol:GDP	0.03	0.038	0.25	3	-10000	0	3
CASP1	-0.01	0.05	0.17	13	-0.16	4	17
PTGES2	0.022	0.006	-10000	0	-10000	0	0
IRF9	0.01	0.04	0.17	6	-0.15	11	17
mol:PI-3-4-5-P3	0.038	0.044	-10000	0	-0.18	9	9
RAP1/GDP	0.029	0.031	-10000	0	-10000	0	0
CBL	-0.006	0.043	0.2	9	-0.17	7	16
MAP3K1	-0.006	0.042	0.2	9	-0.17	2	11
PIAS1	0.022	0.005	-10000	0	-10000	0	0
PIAS4	0.021	0.007	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.032	0.055	-10000	0	-0.21	6	6
PTPN11	-0.004	0.045	0.17	19	-0.17	9	28
CREBBP	0.022	0.005	-10000	0	-10000	0	0
RAPGEF1	0.022	0.006	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.071	-10000	0	-0.35	20	20
alphaV beta3 Integrin	-0.013	0.1	0.21	2	-0.24	89	91
PTK2	-0.018	0.096	-10000	0	-0.37	23	23
positive regulation of JNK cascade	0.002	0.081	-10000	0	-0.29	22	22
CDC42/GDP	0.01	0.11	-10000	0	-0.39	28	28
Rac1/GDP	0.007	0.12	0.3	2	-0.39	29	31
RAP1B	0.023	0.002	-10000	0	-10000	0	0
RAP1A	0.023	0.002	-10000	0	-10000	0	0
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
CDC42/GTP	0.008	0.1	-10000	0	-0.36	22	22
nectin-3/I-afadin	0.021	0.056	-10000	0	-0.25	22	22
RAPGEF1	-0.002	0.1	0.31	4	-0.4	26	30
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.007	0.11	-10000	0	-0.45	27	27
PDGFB-D/PDGFRB	0.009	0.071	-10000	0	-0.35	20	20
TLN1	-0.02	0.058	-10000	0	-0.27	23	23
Rap1/GTP	-0.002	0.078	-10000	0	-0.3	25	25
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.042	0.011	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.021	0.056	-10000	0	-0.25	22	22
PVR	0.022	0.005	-10000	0	-10000	0	0
Necl-5(dimer)	0.022	0.005	-10000	0	-10000	0	0
mol:GDP	-0.003	0.13	0.33	1	-0.47	30	31
MLLT4	0.022	0.005	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
PI3K	0.042	0.066	-10000	0	-0.2	31	31
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.032	0.014	0.21	2	-10000	0	2
positive regulation of lamellipodium assembly	-0.004	0.096	-10000	0	-0.32	31	31
PVRL1	0.023	0.016	0.28	2	-10000	0	2
PVRL3	0.007	0.074	-10000	0	-0.35	22	22
PVRL2	0.022	0.005	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
CDH1	0.019	0.024	-10000	0	-0.35	2	2
CLDN1	-0.02	0.12	-10000	0	-0.35	59	59
JAM-A/CLDN1	0.013	0.082	-10000	0	-0.2	61	61
SRC	-0.01	0.12	-10000	0	-0.49	29	29
ITGB3	-0.04	0.14	0.28	2	-0.35	90	92
nectin-1(dimer)/I-afadin/I-afadin	0.032	0.014	0.21	2	-10000	0	2
FARP2	0.002	0.13	-10000	0	-0.46	25	25
RAC1	0.022	0.005	-10000	0	-10000	0	0
CTNNA1	0.023	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.033	0.051	-10000	0	-0.21	21	21
nectin-1/I-afadin	0.032	0.014	0.21	2	-10000	0	2
nectin-2/I-afadin	0.031	0.01	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.029	0.008	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.032	0.051	-10000	0	-0.21	22	22
CDC42/GTP/IQGAP1/filamentous actin	0.03	0.008	-10000	0	-10000	0	0
F11R	0.019	0.018	-10000	0	-0.35	1	1
positive regulation of filopodium formation	0.002	0.081	-10000	0	-0.29	22	22
alphaV/beta3 Integrin/Talin	-0.021	0.11	0.31	4	-0.3	35	39
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.031	0.01	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.031	0.01	-10000	0	-10000	0	0
PIP5K1C	-0.015	0.064	-10000	0	-0.22	43	43
VAV2	-0.013	0.16	0.34	1	-0.51	35	36
RAP1/GDP	0.013	0.11	0.3	1	-0.36	26	27
ITGAV	0.023	0.003	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.032	0.051	-10000	0	-0.21	21	21
nectin-3(dimer)/I-afadin/I-afadin	0.021	0.056	-10000	0	-0.25	22	22
Rac1/GTP	-0.002	0.12	-10000	0	-0.39	29	29
PTPRM	-0.013	0.075	-10000	0	-0.24	48	48
E-cadherin/beta catenin/alpha catenin	0.054	0.033	-10000	0	-0.17	2	2
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.022	0.005	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.004	0.08	0.18	1	-0.18	82	83
MAPK9	0.005	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.005	0.021	0.12	12	-10000	0	12
GNB1/GNG2	0.026	0.031	0.19	1	-0.2	9	10
GNB1	0.022	0.004	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.005	0.001	-10000	0	-10000	0	0
Gs family/GTP	-0.013	0.068	-10000	0	-0.18	77	77
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.008	0.018	0.051	77	-10000	0	77
GNAL	-0.031	0.13	-10000	0	-0.35	77	77
GNG2	0.017	0.049	0.28	1	-0.35	9	10
CRH	0.022	0.04	0.28	12	-10000	0	12
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.003	0.025	-10000	0	-0.26	5	5
MAPK11	0.004	0.016	-10000	0	-0.26	2	2

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.023	0.004	-10000	0	-10000	0	0
mol:PIP3	-0.029	0.069	-10000	0	-0.25	46	46
FRAP1	0.008	0.058	0.28	2	-0.38	6	8
AKT1	-0.01	0.077	0.16	38	-0.22	40	78
INSR	0.021	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	0.011	0.073	0.27	2	-0.26	4	6
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.036	-10000	0	-0.18	8	8
TSC2	0.022	0.005	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.051	-10000	0	-0.26	3	3
TSC1	0.021	0.017	-10000	0	-0.35	1	1
Insulin Receptor/IRS1	-0.012	0.093	-10000	0	-0.28	58	58
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.006	0.045	-10000	0	-0.2	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.022	0.005	-10000	0	-10000	0	0
RPS6KB1	0.007	0.08	0.26	9	-0.3	11	20
MAP3K5	0.004	0.032	0.2	7	-0.21	6	13
PIK3R1	0.019	0.036	-10000	0	-0.35	5	5
apoptosis	0.004	0.032	0.2	7	-0.21	6	13
mol:LY294002	0	0	-10000	0	-0.001	57	57
EIF4B	0.008	0.077	0.24	12	-0.28	9	21
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.022	0.069	0.26	6	-0.26	8	14
eIF4E/eIF4G1/eIF4A1	0.007	0.032	-10000	0	-0.26	4	4
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.001	0.086	-10000	0	-0.26	49	49
mTOR/RHEB/GTP/Raptor/GBL	0	0.052	0.2	14	-0.15	6	20
FKBP1A	0.023	0.004	-10000	0	-10000	0	0
RHEB/GTP	0.014	0.062	-10000	0	-0.25	3	3
mol:Amino Acids	0	0	-10000	0	-0.001	57	57
FKBP12/Rapamycin	0.017	0.004	-10000	0	-10000	0	0
PDPK1	-0.02	0.077	0.15	34	-0.24	42	76
EIF4E	0.022	0.005	-10000	0	-10000	0	0
ASK1/PP5C	0.023	0.085	-10000	0	-0.52	9	9
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	-0.003	0.079	-10000	0	-0.29	27	27
TSC1/TSC2	0.013	0.079	0.3	3	-0.27	4	7
tumor necrosis factor receptor activity	0	0	0.001	57	-10000	0	57
RPS6	0.022	0.005	-10000	0	-10000	0	0
PPP5C	0.023	0.004	-10000	0	-10000	0	0
EIF4G1	0.021	0.007	-10000	0	-10000	0	0
IRS1	-0.025	0.093	-10000	0	-0.29	58	58
INS	0.016	0.004	-10000	0	-10000	0	0
PTEN	0.021	0.006	-10000	0	-10000	0	0
PDK2	-0.019	0.078	0.15	35	-0.24	40	75
EIF4EBP1	-0.025	0.23	-10000	0	-1	27	27
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
PPP2R5D	0.009	0.064	0.27	9	-0.35	6	15
peptide biosynthetic process	-0.012	0.017	0.18	4	-10000	0	4
RHEB	0.022	0.005	-10000	0	-10000	0	0
EIF4A1	0.021	0.006	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.004	23	-10000	0	23
EEF2	-0.012	0.017	0.18	4	-10000	0	4
eIF4E/4E-BP1	-0.014	0.22	-10000	0	-0.94	27	27

×

Syndecan-3-mediated signaling events

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
CTTN	0.023	0.004	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	0.011	0.098	-10000	0	-0.35	9	9
Syndecan-3/Neurocan	0.018	0.06	0.28	3	-0.37	8	11
POMC	0.027	0.075	0.28	24	-0.35	10	34
EGFR	0.014	0.059	0.33	1	-0.35	13	14
Syndecan-3/EGFR	0.011	0.062	0.3	1	-0.35	11	12
AGRP	0.019	0.017	0.28	2	-10000	0	2
NCSTN	0.019	0.009	-10000	0	-10000	0	0
PSENEN	0.022	0.005	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.018	0.039	-10000	0	-0.35	6	6
APH1A	0.019	0.009	-10000	0	-10000	0	0
NCAN	0.027	0.047	0.29	16	-10000	0	16
long-term memory	0.044	0.064	-10000	0	-0.33	11	11
Syndecan-3/IL8	0.064	0.1	0.26	29	-0.35	11	40
PSEN1	0.022	0.004	-10000	0	-10000	0	0
Src/Cortactin	0.032	0.009	-10000	0	-10000	0	0
FYN	0.023	0.004	-10000	0	-10000	0	0
limb bud formation	0	0.051	-10000	0	-0.39	9	9
MC4R	0.026	0.042	0.28	14	-10000	0	14
SRC	0.022	0.005	-10000	0	-10000	0	0
PTN	-0.06	0.15	-10000	0	-0.35	118	118
FGFR/FGF/Syndecan-3	0	0.051	-10000	0	-0.39	9	9
neuron projection morphogenesis	-0.016	0.084	0.32	3	-0.34	8	11
Syndecan-3/AgRP	0.011	0.055	-10000	0	-0.34	11	11
Syndecan-3/AgRP/MC4R	0.041	0.069	0.27	1	-0.34	10	11
Fyn/Cortactin	0.033	0.007	-10000	0	-10000	0	0
SDC3	0	0.052	-10000	0	-0.39	9	9
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.064	0.1	0.26	29	-0.34	11	40
IL8	0.095	0.12	0.28	152	-10000	0	152
Syndecan-3/Fyn/Cortactin	0.045	0.065	-10000	0	-0.33	11	11
Syndecan-3/CASK	-0.001	0.051	-10000	0	-0.35	11	11
alpha-MSH/MC4R	0.036	0.061	0.22	32	-0.25	10	42
Gamma Secretase	0.045	0.04	-10000	0	-0.18	6	6

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.014	0.091	0.26	8	-0.33	23	31
PDGFB-D/PDGFRB/SLAP	0.025	0.043	0.21	1	-0.24	12	13
PDGFB-D/PDGFRB/APS/CBL	0.036	0.044	-10000	0	-0.2	16	16
AKT1	0.014	0.098	0.31	34	-0.3	1	35
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.02	0.11	0.26	17	-0.36	25	42
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
FGR	-0.013	0.12	0.33	1	-0.54	19	20
mol:Ca2+	0.01	0.11	0.26	15	-0.39	28	43
MYC	0.035	0.15	0.37	20	-0.7	11	31
SHC1	0.019	0.009	-10000	0	-10000	0	0
HRAS/GDP	0.021	0.048	0.17	2	-0.18	17	19
LRP1/PDGFRB/PDGFB	0.034	0.05	-10000	0	-0.21	20	20
GRB10	0.022	0.017	-10000	0	-0.35	1	1
PTPN11	0.023	0.003	-10000	0	-10000	0	0
GO:0007205	0.009	0.11	0.26	15	-0.4	28	43
PTEN	0.021	0.006	-10000	0	-10000	0	0
GRB2	0.022	0.006	-10000	0	-10000	0	0
GRB7	0.038	0.074	0.32	31	-0.35	2	33
PDGFB-D/PDGFRB/SHP2	0.024	0.052	-10000	0	-0.24	19	19
PDGFB-D/PDGFRB/GRB10	0.023	0.053	-10000	0	-0.24	20	20
cell cycle arrest	0.024	0.043	0.21	1	-0.24	12	13
HRAS	0.022	0.005	-10000	0	-10000	0	0
HIF1A	0.01	0.092	0.28	37	-0.27	1	38
GAB1	0.016	0.11	0.29	11	-0.37	25	36
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.018	0.11	0.28	25	-0.32	24	49
PDGFB-D/PDGFRB	0.036	0.043	-10000	0	-0.21	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.024	0.05	-10000	0	-0.24	18	18
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.013	0.077	0.21	4	-0.32	16	20
positive regulation of MAPKKK cascade	0.024	0.051	-10000	0	-0.24	19	19
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
mol:IP3	0.009	0.12	0.26	15	-0.4	28	43
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.02	0.009	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.03	0.069	0.24	22	-0.24	21	43
SHB	0.022	0.004	-10000	0	-10000	0	0
BLK	-0.016	0.14	0.38	2	-0.48	35	37
PTPN2	0.022	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.024	0.05	-10000	0	-0.24	18	18
BCAR1	0.021	0.007	-10000	0	-10000	0	0
VAV2	0.018	0.12	0.29	14	-0.38	25	39
CBL	0.022	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.023	0.052	-10000	0	-0.24	20	20
LCK	-0.001	0.087	0.33	1	-0.5	9	10
PDGFRB	0.009	0.071	-10000	0	-0.35	20	20
ACP1	0.022	0.005	-10000	0	-10000	0	0
HCK	0.006	0.063	0.32	1	-0.91	1	2
ABL1	0.015	0.1	0.25	18	-0.33	25	43
PDGFB-D/PDGFRB/CBL	0.013	0.12	0.3	8	-0.41	31	39
PTPN1	0.021	0.009	-10000	0	-10000	0	0
SNX15	0.022	0.004	-10000	0	-10000	0	0
STAT3	0.022	0.006	-10000	0	-10000	0	0
STAT1	0.024	0.016	0.28	2	-10000	0	2
cell proliferation	0.036	0.14	0.36	21	-0.62	11	32
SLA	0.021	0.013	0.28	1	-10000	0	1
actin cytoskeleton reorganization	-0.005	0.066	0.31	8	-0.33	1	9
SRC	0.003	0.07	0.33	1	-0.82	2	3
PI3K	-0.021	0.025	-10000	0	-0.19	8	8
PDGFB-D/PDGFRB/GRB7/SHC	0.036	0.06	0.23	21	-0.2	16	37
SH2B2	0.022	0.005	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.02	0.11	0.27	16	-0.38	25	41
LYN	0.003	0.055	0.33	1	-0.44	2	3
LRP1	0.022	0.023	-10000	0	-0.35	2	2
SOS1	0.023	0.003	-10000	0	-10000	0	0
STAT5B	0.02	0.023	-10000	0	-0.35	2	2
STAT5A	0.021	0.017	-10000	0	-0.35	1	1
NCK1-2/p130 Cas	0.05	0.049	-10000	0	-0.18	12	12
SPHK1	0.024	0.022	0.31	3	-10000	0	3
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.009	0.12	0.26	15	-0.4	28	43
PLCG1	0.009	0.12	0.26	15	-0.41	28	43
NHERF/PDGFRB	0.037	0.047	0.2	4	-0.2	17	21
YES1	-0.005	0.087	-10000	0	-0.43	15	15
cell migration	0.036	0.047	0.2	4	-0.2	17	21
SHC/Grb2/SOS1	0.044	0.045	-10000	0	-0.17	9	9
SLC9A3R2	0.022	0.005	-10000	0	-10000	0	0
SLC9A3R1	0.024	0.023	0.28	4	-10000	0	4
NHERF1-2/PDGFRB/PTEN	0.045	0.047	-10000	0	-0.18	16	16
FYN	0.003	0.068	0.33	1	-0.61	3	4
DOK1	-0.007	0.05	0.17	26	-0.19	13	39
HRAS/GTP	0.016	0.004	-10000	0	-10000	0	0
PDGFB	0.022	0.006	-10000	0	-10000	0	0
RAC1	0.016	0.13	0.34	10	-0.44	25	35
PRKCD	-0.005	0.051	0.18	29	-0.19	11	40
FER	-0.006	0.051	0.18	28	-0.19	12	40
MAPKKK cascade	0.028	0.098	0.19	119	-0.18	1	120
RASA1	-0.007	0.056	0.18	29	-0.2	16	45
NCK1	0.021	0.023	-10000	0	-0.35	2	2
NCK2	0.023	0.002	-10000	0	-10000	0	0
p62DOK/Csk	0.023	0.044	0.16	21	-0.18	12	33
PDGFB-D/PDGFRB/SHB	0.023	0.051	-10000	0	-0.24	19	19
chemotaxis	0.015	0.099	0.25	19	-0.32	25	44
STAT1-3-5/STAT1-3-5	0.043	0.044	-10000	0	-0.19	10	10
Bovine Papilomavirus E5/PDGFRB	0.008	0.049	-10000	0	-0.24	20	20
PTPRJ	0.022	0.004	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.069	0.13	-10000	0	-0.36	39	39
CaM/Ca2+	0.017	0.003	-10000	0	-10000	0	0
AKT1	0.023	0.004	-10000	0	-10000	0	0
AKT2	0.022	0.005	-10000	0	-10000	0	0
STXBP4	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.077	0.14	0.25	2	-0.38	44	46
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
CALM1	0.022	0.004	-10000	0	-10000	0	0
YWHAQ	0.022	0.005	-10000	0	-10000	0	0
TBC1D4	-0.012	0.015	-10000	0	-0.25	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.022	0.006	-10000	0	-10000	0	0
YWHAB	0.022	0.005	-10000	0	-10000	0	0
SNARE/Synip	0.041	0.016	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
ASIP	0.02	0.013	0.28	1	-10000	0	1
PRKCI	0.021	0.007	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.017	0.003	-10000	0	-10000	0	0
RHOQ	0.023	0.003	-10000	0	-10000	0	0
GYS1	0.006	0.014	0.24	2	-10000	0	2
PRKCZ	0.022	0.02	0.28	1	-0.35	1	2
TRIP10	0.021	0.006	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.029	0.009	-10000	0	-10000	0	0
AS160/14-3-3	0.052	0.055	0.24	6	-0.25	6	12
VAMP2	0.021	0.007	-10000	0	-10000	0	0
SLC2A4	-0.085	0.15	0.31	1	-0.42	44	45
STX4	0.022	0.005	-10000	0	-10000	0	0
GSK3B	0.014	0.005	-10000	0	-10000	0	0
SFN	0.21	0.12	0.28	385	-10000	0	385
LNPEP	0.022	0.004	-10000	0	-10000	0	0
YWHAE	0.021	0.007	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.019	0.055	-10000	0	-10000	0	0
UGCG	-0.03	0.18	-10000	0	-0.64	42	42
AKT1/mTOR/p70S6K/Hsp90/TERT	0.043	0.14	0.28	8	-0.5	17	25
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.028	0.18	-10000	0	-0.62	43	43
mol:DAG	0.004	0.094	-10000	0	-0.77	7	7
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.15	0.26	2	-0.39	44	46
FRAP1	0.007	0.17	0.28	2	-0.44	48	50
FOXO3	0.02	0.14	0.32	7	-0.5	16	23
AKT1	0.02	0.15	0.29	2	-0.53	17	19
GAB2	0.018	0.033	-10000	0	-0.35	4	4
SMPD1	-0.007	0.14	-10000	0	-0.63	23	23
SGMS1	0.012	0.072	-10000	0	-0.58	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	-0.008	0.02	-10000	0	-0.21	5	5
CALM1	0.022	0.004	-10000	0	-10000	0	0
cell proliferation	0.01	0.14	0.25	3	-0.45	29	32
EIF3A	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.026	0.032	-10000	0	-0.25	5	5
RPS6KB1	0.005	0.14	-10000	0	-0.81	15	15
mol:sphingomyelin	0.004	0.094	-10000	0	-0.77	7	7
natural killer cell activation	0	0.003	-10000	0	-0.016	1	1
JAK3	0.023	0.024	0.28	4	-10000	0	4
PIK3R1	0.018	0.037	-10000	0	-0.35	5	5
JAK1	0.022	0.018	-10000	0	-0.35	1	1
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
MYC	0.039	0.17	0.38	5	-0.85	11	16
MYB	0.052	0.082	0.48	2	-0.78	1	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.025	0.094	0.24	1	-0.46	8	9
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.027	0.13	-10000	0	-0.72	15	15
mol:PI-3-4-5-P3	0.029	0.095	0.24	1	-0.44	8	9
Rac1/GDP	0.011	0.023	-10000	0	-0.18	5	5
T cell proliferation	0.028	0.094	0.23	9	-0.4	9	18
SHC1	0.018	0.011	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.007	0.016	0.055	53	-10000	0	53
PRKCZ	0.027	0.095	0.24	5	-0.42	9	14
NF kappa B1 p50/RelA	0.026	0.15	-10000	0	-0.4	40	40
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.014	0.048	-10000	0	-0.41	3	3
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
RELA	0.022	0.004	-10000	0	-10000	0	0
IL2RA	0.029	0.053	0.28	20	-0.35	1	21
IL2RB	0.021	0.018	-10000	0	-0.35	1	1
TERT	0.12	0.13	0.28	194	-10000	0	194
E2F1	0.055	0.08	0.3	7	-0.9	1	8
SOS1	0.021	0.01	-10000	0	-10000	0	0
RPS6	0.022	0.005	-10000	0	-10000	0	0
mol:cAMP	-0.004	0.008	-10000	0	-0.028	52	52
PTPN11	0.02	0.012	-10000	0	-10000	0	0
IL2RG	0.023	0.04	0.28	6	-0.35	3	9
actin cytoskeleton organization	0.028	0.094	0.23	9	-0.4	9	18
GRB2	0.02	0.01	-10000	0	-10000	0	0
IL2	0.024	0.048	0.28	17	-10000	0	17
PIK3CA	0.019	0.019	-10000	0	-0.35	1	1
Rac1/GTP	0.032	0.032	-10000	0	-0.17	5	5
LCK	0.023	0.029	0.28	4	-0.35	1	5
BCL2	-0.03	0.26	-10000	0	-0.76	54	54

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.003	0.12	0.41	2	-0.49	2	4
RAD9A	0.022	0.004	-10000	0	-10000	0	0
AP1	-0.047	0.13	-10000	0	-0.25	162	162
IFNAR2	0.028	0.018	-10000	0	-0.34	1	1
AKT1	0.009	0.061	0.18	6	-0.16	38	44
ER alpha/Oestrogen	-0.007	0.079	-10000	0	-0.24	56	56
NFX1/SIN3/HDAC complex	0.018	0.059	-10000	0	-0.35	9	9
EGF	0.033	0.055	0.28	21	-0.34	2	23
SMG5	0.019	0.009	-10000	0	-10000	0	0
SMG6	0.021	0.006	-10000	0	-10000	0	0
SP3/HDAC2	0.042	0.013	-10000	0	-10000	0	0
TERT/c-Abl	0.001	0.12	0.39	1	-0.57	1	2
SAP18	0.023	0.005	-10000	0	-10000	0	0
MRN complex	0.041	0.016	-10000	0	-10000	0	0
WT1	-0.24	0.17	-10000	0	-0.35	384	384
WRN	0.02	0.008	-10000	0	-10000	0	0
SP1	0.03	0.01	-10000	0	-10000	0	0
SP3	0.025	0.004	-10000	0	-10000	0	0
TERF2IP	0.02	0.008	-10000	0	-10000	0	0
Telomerase/Nucleolin	0	0.11	-10000	0	-0.51	1	1
Mad/Max	0.039	0.012	-10000	0	-10000	0	0
TERT	0.003	0.13	0.45	1	-0.5	2	3
CCND1	0.005	0.12	0.41	2	-0.5	1	3
MAX	0.025	0.005	-10000	0	-10000	0	0
RBBP7	0.024	0.004	-10000	0	-10000	0	0
RBBP4	0.021	0.028	-10000	0	-0.35	3	3
TERF2	0.018	0.01	-10000	0	-10000	0	0
PTGES3	0.023	0.003	-10000	0	-10000	0	0
SIN3A	0.023	0.005	-10000	0	-10000	0	0
Telomerase/911	0.025	0.042	0.21	2	-0.29	2	4
CDKN1B	-0.001	0.1	-10000	0	-0.46	23	23
RAD1	0.022	0.004	-10000	0	-10000	0	0
XRCC5	0.023	0.003	-10000	0	-10000	0	0
XRCC6	0.022	0.006	-10000	0	-10000	0	0
SAP30	0.023	0.005	-10000	0	-10000	0	0
TRF2/PARP2	0.029	0.013	-10000	0	-10000	0	0
UBE3A	0.024	0.006	-10000	0	-10000	0	0
JUN	0.02	0.042	-10000	0	-0.35	7	7
E6	0.002	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.022	0.008	-10000	0	-10000	0	0
FOS	-0.086	0.17	-10000	0	-0.35	160	160
IFN-gamma/IRF1	0.05	0.084	0.22	60	-0.25	23	83
PARP2	0.022	0.004	-10000	0	-10000	0	0
BLM	0.051	0.081	0.28	59	-10000	0	59
Telomerase	0.027	0.085	0.22	4	-0.46	6	10
IRF1	0.02	0.036	-10000	0	-0.15	23	23
ESR1	-0.016	0.11	-10000	0	-0.35	56	56
KU/TER	0.032	0.009	-10000	0	-10000	0	0
ATM/TRF2	0.03	0.012	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.021	0.058	-10000	0	-0.3	11	11
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.021	0.059	-10000	0	-0.31	11	11
HDAC1	0.024	0.004	-10000	0	-10000	0	0
HDAC2	0.029	0.009	-10000	0	-10000	0	0
ATM	0.015	0.019	-10000	0	-10000	0	0
SMAD3	-0.015	0.021	-10000	0	-0.25	4	4
ABL1	0.02	0.023	-10000	0	-0.35	2	2
MXD1	0.025	0.005	-10000	0	-10000	0	0
MRE11A	0.022	0.004	-10000	0	-10000	0	0
HUS1	0.022	0.004	-10000	0	-10000	0	0
RPS6KB1	0.022	0.005	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.022	0.12	0.38	1	-0.48	2	3
NR2F2	-0.011	0.078	-10000	0	-0.35	25	25
MAPK3	0.002	0.025	0.11	17	-10000	0	17
MAPK1	0.002	0.024	0.11	16	-10000	0	16
TGFB1/TGF beta receptor Type II	0.02	0.017	-10000	0	-0.35	1	1
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
HNRNPC	0.022	0.004	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.015	0.019	-10000	0	-10000	0	0
NBN	0.021	0.007	-10000	0	-10000	0	0
EGFR	0.016	0.059	0.33	1	-0.35	13	14
mol:Oestrogen	0.001	0.002	-10000	0	-10000	0	0
EGF/EGFR	0.036	0.058	0.21	21	-0.24	14	35
MYC	0.016	0.046	-10000	0	-0.35	8	8
IL2	0.034	0.047	0.29	17	-10000	0	17
KU	0.032	0.009	-10000	0	-10000	0	0
RAD50	0.023	0.003	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
TGFB1	0.02	0.017	-10000	0	-0.35	1	1
TRF2/BLM	0.044	0.051	0.2	48	-10000	0	48
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.009	0.12	0.41	1	-0.53	1	2
SP1/HDAC2	0.048	0.02	-10000	0	-10000	0	0
PINX1	0.02	0.008	-10000	0	-10000	0	0
Telomerase/EST1A	-0.003	0.11	-10000	0	-0.51	1	1
Smad3/Myc	0.003	0.036	-10000	0	-0.23	9	9
911 complex	0.043	0.013	-10000	0	-10000	0	0
IFNG	0.047	0.091	0.28	60	-0.15	23	83
Telomerase/PinX1	-0.005	0.11	-10000	0	-0.51	1	1
Telomerase/AKT1/mTOR/p70S6K	0.018	0.076	0.27	3	-0.36	10	13
SIN3B	0.023	0.006	-10000	0	-10000	0	0
YWHAE	0.021	0.007	-10000	0	-10000	0	0
Telomerase/EST1B	0.001	0.1	-10000	0	-0.51	1	1
response to DNA damage stimulus	0.004	0.019	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.052	0.028	-10000	0	-10000	0	0
TRF2/WRN	0.027	0.015	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.001	0.11	-10000	0	-0.51	1	1
E2F1	0.077	0.1	0.29	100	-10000	0	100
ZNFX1	0.023	0.005	-10000	0	-10000	0	0
PIF1	0.087	0.11	0.28	135	-10000	0	135
NCL	0.023	0.003	-10000	0	-10000	0	0
DKC1	0.023	0.003	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	-0.007	0.009	-10000	0	-10000	0	0
RAS family/GTP	0.042	0.075	0.24	2	-0.22	7	9
NFATC4	-0.004	0.077	0.34	15	-0.2	1	16
ERBB2IP	0.021	0.009	-10000	0	-10000	0	0
HSP90 (dimer)	0.022	0.004	-10000	0	-10000	0	0
mammary gland morphogenesis	0.004	0.051	0.19	1	-0.21	10	11
JUN	0.007	0.085	0.25	5	-0.33	4	9
HRAS	0.022	0.005	-10000	0	-10000	0	0
DOCK7	-0.016	0.054	0.29	3	-0.21	7	10
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.027	0.045	0.21	12	-0.2	8	20
AKT1	-0.003	0.008	-10000	0	-10000	0	0
BAD	-0.008	0.005	-10000	0	-10000	0	0
MAPK10	-0.023	0.076	0.21	19	-0.18	9	28
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.007	0.058	0.34	2	-0.22	10	12
RAF1	0.035	0.088	0.27	14	-0.25	6	20
ErbB2/ErbB3/neuregulin 2	-0.003	0.081	0.2	10	-0.2	68	78
STAT3	-0.011	0.17	-10000	0	-0.78	25	25
cell migration	-0.011	0.089	0.24	28	-0.2	9	37
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.025	0.23	0.37	4	-0.56	32	36
FOS	-0.076	0.26	0.32	6	-0.44	168	174
NRAS	0.023	0.002	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.051	0.19	1	-0.21	10	11
MAPK3	0	0.19	0.35	7	-0.57	24	31
MAPK1	-0.005	0.2	0.34	4	-0.6	24	28
JAK2	-0.018	0.053	0.29	3	-0.21	5	8
NF2	0.005	0.028	-10000	0	-0.64	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.009	0.041	0.18	5	-0.22	9	14
NRG1	0.014	0.05	0.28	1	-0.35	9	10
GRB2/SOS1	0.032	0.01	-10000	0	-10000	0	0
MAPK8	-0.002	0.067	0.28	4	-0.24	14	18
MAPK9	0	0.062	0.22	23	-10000	0	23
ERBB2	-0.009	0.056	0.32	14	-10000	0	14
ERBB3	0.02	0.028	-10000	0	-0.35	3	3
SHC1	0.019	0.009	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
apoptosis	0.007	0.008	-10000	0	-10000	0	0
STAT3 (dimer)	-0.011	0.17	-10000	0	-0.76	26	26
RNF41	-0.01	0.008	-10000	0	-10000	0	0
FRAP1	-0.003	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.017	0.031	-10000	0	-0.16	9	9
ErbB2/ErbB2/HSP90 (dimer)	-0.01	0.035	0.21	12	-10000	0	12
CHRNA1	0.025	0.16	0.34	7	-0.37	20	27
myelination	0.013	0.1	0.32	39	-10000	0	39
PPP3CB	-0.016	0.049	0.29	2	-0.2	7	9
KRAS	0.023	0.014	0.33	1	-10000	0	1
RAC1-CDC42/GDP	0.044	0.056	0.22	4	-0.2	8	12
NRG2	-0.03	0.13	-10000	0	-0.35	75	75
mol:GDP	0.009	0.041	0.18	5	-0.22	9	14
SOS1	0.023	0.004	-10000	0	-10000	0	0
MAP2K2	0.028	0.092	0.21	40	-0.28	5	45
SRC	0.022	0.005	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.016	0.053	0.29	3	-0.2	7	10
MAP2K1	-0.008	0.19	0.39	2	-0.56	26	28
heart morphogenesis	0.004	0.051	0.19	1	-0.21	10	11
RAS family/GDP	0.048	0.069	0.24	4	-0.22	6	10
GRB2	0.022	0.006	-10000	0	-10000	0	0
PRKACA	0.008	0.039	-10000	0	-0.61	2	2
CHRNE	0.006	0.025	0.097	1	-0.16	4	5
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
activation of caspase activity	0.003	0.008	-10000	0	-10000	0	0
nervous system development	0.004	0.051	0.19	1	-0.21	10	11
CDC42	0.022	0.005	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.011	0.011	-10000	0	-0.25	1	1
MAP4K4	0.007	0.057	0.21	4	-0.28	7	11
BAG4	0.019	0.024	-10000	0	-0.35	2	2
PKC zeta/ceramide	0.013	0.041	0.2	1	-0.19	18	19
NFKBIA	0.022	0.004	-10000	0	-10000	0	0
BIRC3	0.018	0.045	0.28	2	-0.35	7	9
BAX	0.003	0.049	-10000	0	-0.33	10	10
RIPK1	0.022	0.004	-10000	0	-10000	0	0
AKT1	0	0.081	0.65	8	-10000	0	8
BAD	-0.001	0.044	0.2	10	-0.18	19	29
SMPD1	0.012	0.058	0.16	24	-0.22	14	38
RB1	-0.005	0.036	0.2	1	-0.18	20	21
FADD/Caspase 8	0.011	0.065	0.23	4	-0.31	10	14
MAP2K4	-0.006	0.039	0.18	6	-0.17	20	26
NSMAF	0.021	0.007	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.003	0.047	0.2	12	-0.17	21	33
EGF	0.031	0.055	0.28	21	-0.35	2	23
mol:ceramide	-0.001	0.038	0.12	2	-0.19	19	21
MADD	0.022	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.01	0.011	-10000	0	-0.25	1	1
ASAH1	0.02	0.008	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.005	0.036	0.2	1	-0.18	20	21
cell proliferation	-0.013	0.075	0.18	1	-0.22	16	17
BID	-0.013	0.17	-10000	0	-0.62	33	33
MAP3K1	-0.004	0.038	0.18	4	-0.18	19	23
EIF2A	0.002	0.055	0.18	34	-0.17	14	48
TRADD	0.02	0.008	-10000	0	-10000	0	0
CRADD	0.023	0.002	-10000	0	-10000	0	0
MAPK3	-0.004	0.048	0.2	11	-0.18	11	22
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.007	0.051	0.19	12	-0.19	12	24
Cathepsin D/ceramide	0.014	0.039	0.18	1	-0.18	18	19
FADD	0.007	0.06	0.21	6	-0.28	8	14
KSR1	-0.003	0.043	0.2	7	-0.18	21	28
MAPK8	-0.003	0.051	-10000	0	-0.2	12	12
PRKRA	-0.002	0.04	0.19	6	-0.18	18	24
PDGFA	0.021	0.017	-10000	0	-0.35	1	1
TRAF2	0.022	0.006	-10000	0	-10000	0	0
IGF1	-0.046	0.14	-10000	0	-0.35	100	100
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.001	0.037	0.12	2	-0.19	19	21
CTSD	0.022	0.012	0.28	1	-10000	0	1
regulation of nitric oxide biosynthetic process	0.032	0.015	-10000	0	-0.24	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.013	0.079	0.2	1	-0.23	16	17
PRKCD	0.022	0.005	-10000	0	-10000	0	0
PRKCZ	0.022	0.02	0.28	1	-0.35	1	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.01	0.011	-10000	0	-0.25	1	1
RelA/NF kappa B1	0.032	0.015	-10000	0	-0.25	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.023	0.002	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.011	0.052	0.23	1	-0.38	2	3
TNFR1A/BAG4/TNF-alpha	0.054	0.054	0.2	51	-0.21	2	53
mol:Sphingosine-1-phosphate	-0.011	0.011	-10000	0	-0.24	1	1
MAP2K1	-0.006	0.046	0.19	13	-0.17	16	29
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.022	0.004	-10000	0	-10000	0	0
CYCS	0.016	0.051	0.14	41	-0.17	5	46
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
TNFR1A/BAG4	0.029	0.021	-10000	0	-0.25	2	2
EIF2AK2	-0.003	0.044	0.2	12	-0.18	17	29
TNF-alpha/TNFR1A/FAN	0.056	0.052	0.2	52	-0.21	1	53
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.019	0.058	-10000	0	-0.36	7	7
MAP2K2	-0.006	0.046	0.19	12	-0.17	16	28
SMPD3	0.003	0.088	0.2	8	-0.27	39	47
TNF	0.053	0.088	0.28	66	-0.35	2	68
PKC zeta/PAR4	0.033	0.016	0.21	1	-0.25	1	2
mol:PHOSPHOCHOLINE	-0.001	0.036	0.14	4	-0.13	13	17
NF kappa B1/RelA/I kappa B alpha	0.061	0.026	-10000	0	-0.18	2	2
AIFM1	0.014	0.052	0.15	16	-0.16	7	23
BCL2	-0.008	0.1	-10000	0	-0.35	44	44

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	0.048	0.051	0.23	10	-0.19	14	24
MAP4K1	0.028	0.04	0.29	12	-10000	0	12
MAP3K8	0.02	0.028	-10000	0	-0.35	3	3
PRKCB	0.001	0.087	-10000	0	-0.35	31	31
DBNL	0.023	0.004	-10000	0	-10000	0	0
CRKL	0.022	0.005	-10000	0	-10000	0	0
MAP3K1	0.007	0.045	-10000	0	-0.24	4	4
JUN	-0.044	0.19	-10000	0	-0.56	60	60
MAP3K7	0.006	0.047	-10000	0	-0.26	3	3
GRAP2	0.011	0.061	-10000	0	-0.35	15	15
CRK	0.021	0.006	-10000	0	-10000	0	0
MAP2K4	0.005	0.061	-10000	0	-0.25	14	14
LAT	0.022	0.005	-10000	0	-10000	0	0
LCP2	0.023	0.012	0.28	1	-10000	0	1
MAPK8	-0.04	0.2	-10000	0	-0.58	60	60
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.014	0.049	-10000	0	-0.2	11	11
LAT/GRAP2/SLP76/HPK1/HIP-55	0.056	0.049	0.27	3	-0.18	11	14

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.022	0.015	0.33	1	-10000	0	1
NFATC1	0.012	0.08	0.27	4	-0.39	5	9
NFATC2	-0.001	0.066	0.14	9	-0.21	22	31
NFATC3	0.012	0.016	-10000	0	-0.3	1	1
YWHAE	0.021	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.022	0.12	0.21	4	-0.35	35	39
Exportin 1/Ran/NUP214	0.043	0.014	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.001	0.1	-10000	0	-0.32	27	27
BCL2/BAX	0.009	0.077	-10000	0	-0.25	44	44
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.015	0.01	-10000	0	-10000	0	0
BAX	0.023	0.004	-10000	0	-10000	0	0
MAPK14	0.022	0.005	-10000	0	-10000	0	0
BAD	0.022	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.009	0.1	-10000	0	-0.35	26	26
Calcineurin A alpha-beta B1/BCL2	-0.008	0.1	-10000	0	-0.35	44	44
FKBP8	0.022	0.005	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.009	0.1	0.35	26	-10000	0	26
KPNB1	0.022	0.005	-10000	0	-10000	0	0
KPNA2	0.035	0.059	0.3	25	-10000	0	25
XPO1	0.023	0.003	-10000	0	-10000	0	0
SFN	0.21	0.12	0.28	385	-10000	0	385
MAP3K8	0.02	0.028	-10000	0	-0.35	3	3
NFAT4/CK1 alpha	0.017	0.022	-10000	0	-0.16	1	1
MEF2D/NFAT1/Cbp/p300	0.012	0.088	-10000	0	-0.24	34	34
CABIN1	-0.023	0.12	0.21	4	-0.36	34	38
CALM1	0.02	0.01	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
MAP3K1	0.022	0.005	-10000	0	-10000	0	0
CAMK4	0.023	0.037	0.28	5	-0.35	3	8
mol:Ca2+	0	0.003	-10000	0	-10000	0	0
MAPK3	0.022	0.005	-10000	0	-10000	0	0
YWHAH	0.022	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.03	0.019	-10000	0	-0.25	2	2
YWHAB	0.022	0.005	-10000	0	-10000	0	0
MAPK8	0.018	0.036	-10000	0	-0.35	5	5
MAPK9	0.023	0.004	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
FKBP1A	0.022	0.004	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.013	0.085	0.26	3	-0.37	7	10
PRKCH	0.021	0.023	-10000	0	-0.35	2	2
CABIN1/Cbp/p300	0.028	0.019	-10000	0	-10000	0	0
CASP3	0.022	0.006	-10000	0	-10000	0	0
PIM1	0.023	0.003	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.014	0.007	-10000	0	-10000	0	0
apoptosis	0.008	0.031	0.19	1	-0.25	2	3
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.049	0.058	0.2	6	-0.29	6	12
PRKCB	0.001	0.087	-10000	0	-0.35	31	31
PRKCE	0.023	0.003	-10000	0	-10000	0	0
JNK2/NFAT4	0.012	0.053	-10000	0	-0.27	1	1
BAD/BCL-XL	0.032	0.014	0.24	1	-10000	0	1
PRKCD	0.022	0.005	-10000	0	-10000	0	0
NUP214	0.022	0.006	-10000	0	-10000	0	0
PRKCZ	0.022	0.02	0.28	1	-0.35	1	2
PRKCA	0	0.087	-10000	0	-0.35	31	31
PRKCG	0.049	0.095	0.28	65	-0.35	6	71
PRKCQ	-0.007	0.1	0.28	1	-0.35	43	44
FKBP38/BCL2	0.009	0.077	-10000	0	-0.25	44	44
EP300	0.019	0.012	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
NFATc/JNK1	0.023	0.079	0.28	3	-0.37	5	8
CaM/Ca2+/FKBP38	0.026	0.015	-10000	0	-10000	0	0
FKBP12/FK506	0.017	0.003	-10000	0	-10000	0	0
CSNK1A1	0.008	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.027	0.027	0.19	5	-0.2	3	8
NFATc/ERK1	0.023	0.078	0.28	3	-0.37	5	8
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.002	0.11	-10000	0	-0.32	33	33
NR4A1	0.01	0.13	0.23	16	-0.38	32	48
GSK3B	0.022	0.006	-10000	0	-10000	0	0
positive T cell selection	0.012	0.016	-10000	0	-0.3	1	1
NFAT1/CK1 alpha	0.002	0.048	0.12	1	-0.18	13	14
RCH1/ KPNB1	0.04	0.04	0.22	24	-10000	0	24
YWHAQ	0.022	0.005	-10000	0	-10000	0	0
PRKACA	0.021	0.006	-10000	0	-10000	0	0
AKAP5	0.021	0.023	-10000	0	-0.35	2	2
MEF2D	0.017	0.013	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
NFATc/p38 alpha	0.022	0.078	0.28	3	-0.37	5	8
CREBBP	0.019	0.012	-10000	0	-10000	0	0
BCL2	-0.008	0.1	-10000	0	-0.35	44	44

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.004	0.048	-10000	0	-10000	0	0
PLK1	0.13	0.19	0.47	12	-0.61	5	17
CDKN1B	0.06	0.16	0.38	7	-0.41	28	35
FOXO3	0.1	0.18	0.41	20	-0.55	11	31
KAT2B	0.028	0.056	-10000	0	-0.34	8	8
FOXO1/SIRT1	0.012	0.046	0.25	1	-0.21	1	2
CAT	0.093	0.18	0.52	4	-0.66	5	9
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
AKT1	0.035	0.033	-10000	0	-10000	0	0
FOXO1	0.007	0.052	0.25	4	-0.22	1	5
MAPK10	-0.016	0.081	0.2	11	-0.17	108	119
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
FOXO4	0.007	0.079	0.3	3	-0.35	2	5
response to oxidative stress	0.017	0.023	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.083	0.17	0.37	14	-0.45	19	33
XPO1	0.023	0.003	-10000	0	-10000	0	0
EP300	0.022	0.007	-10000	0	-10000	0	0
BCL2L11	0.037	0.092	-10000	0	-0.74	6	6
FOXO1/SKP2	0.018	0.048	0.28	1	-10000	0	1
mol:GDP	0.017	0.023	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
GADD45A	0.071	0.12	-10000	0	-0.64	2	2
YWHAQ	0.022	0.005	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.034	0.14	0.24	3	-0.53	25	28
MST1	0.036	0.043	0.29	6	-10000	0	6
CSNK1D	0.022	0.006	-10000	0	-10000	0	0
CSNK1E	0.022	0.006	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.049	0.12	0.24	1	-0.45	21	22
YWHAB	0.022	0.005	-10000	0	-10000	0	0
MAPK8	0.018	0.036	0.21	10	-0.16	5	15
MAPK9	0.021	0.033	0.2	13	-10000	0	13
YWHAG	0.022	0.004	-10000	0	-10000	0	0
YWHAE	0.021	0.007	-10000	0	-10000	0	0
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
SIRT1	0.013	0.027	-10000	0	-0.35	2	2
SOD2	0.078	0.14	0.44	5	-0.49	4	9
RBL2	0.031	0.26	0.45	1	-0.69	41	42
RAL/GDP	0.04	0.025	-10000	0	-10000	0	0
CHUK	0.033	0.032	-10000	0	-10000	0	0
Ran/GTP	0.018	0.003	-10000	0	-10000	0	0
CSNK1G2	0.021	0.006	-10000	0	-10000	0	0
RAL/GTP	0.041	0.024	-10000	0	-10000	0	0
CSNK1G1	0.022	0.005	-10000	0	-10000	0	0
FASLG	0.038	0.11	-10000	0	-1.2	4	4
SKP2	0.022	0.005	-10000	0	-10000	0	0
USP7	0.023	0.005	-10000	0	-10000	0	0
IKBKB	0.029	0.032	-10000	0	-10000	0	0
CCNB1	0.1	0.18	0.45	11	-0.62	5	16
FOXO1-3a-4/beta catenin	0.07	0.12	0.37	8	-0.37	5	13
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.048	0.28	1	-10000	0	1
CSNK1A1	0.023	0.004	-10000	0	-10000	0	0
SGK1	0.033	0.037	-10000	0	-0.37	1	1
CSNK1G3	0.023	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.033	0.007	-10000	0	-10000	0	0
ZFAND5	0.007	0.071	0.32	1	-10000	0	1
SFN	0.21	0.12	0.28	385	-10000	0	385
CDK2	0.022	0.005	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.068	0.12	0.25	5	-0.44	18	23
CREBBP	0.022	0.006	-10000	0	-10000	0	0
FBXO32	0.023	0.4	0.5	29	-0.96	68	97
BCL6	0.085	0.16	0.45	1	-0.67	5	6
RALB	0.023	0.003	-10000	0	-10000	0	0
RALA	0.023	0.004	-10000	0	-10000	0	0
YWHAH	0.022	0.006	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.019	0.024	-10000	0	-0.35	2	2
Caspase 8 (4 units)	0.029	0.048	-10000	0	-0.24	6	6
NEF	0.001	0.019	-10000	0	-0.2	4	4
NFKBIA	0.022	0.014	-10000	0	-10000	0	0
BIRC3	0.011	0.057	0.2	2	-0.41	7	9
CYCS	0.024	0.067	0.17	71	-0.24	6	77
RIPK1	0.022	0.004	-10000	0	-10000	0	0
CD247	0.02	0.03	0.33	1	-0.25	4	5
MAP2K7	0.004	0.19	-10000	0	-0.67	33	33
protein ubiquitination	0.01	0.076	0.28	7	-0.29	8	15
CRADD	0.023	0.002	-10000	0	-10000	0	0
DAXX	0.023	0.003	-10000	0	-10000	0	0
FAS	0.019	0.032	-10000	0	-0.35	4	4
BID	0.03	0.069	0.18	72	-0.25	6	78
NF-kappa-B/RelA/I kappa B alpha	0.044	0.037	-10000	0	-0.22	8	8
TRADD	0.02	0.008	-10000	0	-10000	0	0
MAP3K5	0.022	0.016	-10000	0	-0.35	1	1
CFLAR	0.023	0.003	-10000	0	-10000	0	0
FADD	0.022	0.004	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.044	0.037	-10000	0	-0.23	8	8
MAPK8	0.006	0.18	0.4	5	-0.62	33	38
APAF1	0.023	0.002	-10000	0	-10000	0	0
TRAF1	0.022	0.005	-10000	0	-10000	0	0
TRAF2	0.022	0.006	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.037	0.071	0.19	72	-0.26	6	78
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.004	0.089	0.21	3	-0.34	15	18
CHUK	0.011	0.078	0.29	7	-0.31	8	15
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.058	0.033	-10000	0	-0.18	5	5
TCRz/NEF	0.018	0.03	0.16	7	-0.24	4	11
TNF	0.053	0.088	0.28	66	-0.35	2	68
FASLG	0.012	0.045	0.25	8	-0.33	4	12
NFKB1	0.021	0.021	-10000	0	-0.35	1	1
TNFR1A/BAG4/TNF-alpha	0.054	0.054	0.2	51	-0.21	2	53
CASP6	0.041	0.1	-10000	0	-0.46	14	14
CASP7	0.031	0.1	0.35	9	-0.43	9	18
RELA	0.022	0.014	-10000	0	-10000	0	0
CASP2	0.022	0.005	-10000	0	-10000	0	0
CASP3	0.03	0.1	0.36	10	-0.4	12	22
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.029	0.021	-10000	0	-0.25	2	2
CASP8	0.023	0.003	-10000	0	-10000	0	0
CASP9	0.022	0.005	-10000	0	-10000	0	0
MAP3K14	0.009	0.081	0.2	2	-0.33	12	14
APAF-1/Caspase 9	0.029	0.058	-10000	0	-0.29	7	7
BCL2	-0.006	0.17	0.38	4	-0.58	32	36

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	0.19	0.26	0.66	8	-1.2	7	15
IL23A	0.2	0.24	0.72	9	-1.2	4	13
NF kappa B1 p50/RelA/I kappa B alpha	0.18	0.22	0.58	3	-1.1	5	8
positive regulation of T cell mediated cytotoxicity	0.21	0.26	0.66	20	-1.2	5	25
ITGA3	0.19	0.24	0.65	9	-1.2	4	13
IL17F	0.15	0.19	0.49	31	-0.68	5	36
IL12B	0.063	0.049	0.2	9	-10000	0	9
STAT1 (dimer)	0.19	0.24	0.61	8	-1.2	5	13
CD4	0.2	0.23	0.64	9	-1.1	4	13
IL23	0.19	0.24	0.67	8	-1.2	4	12
IL23R	0.1	0.097	0.44	2	-0.58	2	4
IL1B	0.2	0.25	0.72	8	-1.1	7	15
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.22	0.25	0.67	21	-1.1	4	25
TYK2	0.044	0.034	-10000	0	-10000	0	0
STAT4	0.022	0.016	-10000	0	-0.35	1	1
STAT3	0.022	0.006	-10000	0	-10000	0	0
IL18RAP	0.022	0.038	0.29	3	-0.35	4	7
IL12RB1	0.049	0.067	0.35	13	-0.38	4	17
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
IL12Rbeta1/TYK2	0.058	0.059	0.28	12	-0.27	4	16
IL23R/JAK2	0.13	0.12	0.45	2	-0.48	1	3
positive regulation of chronic inflammatory response	0.21	0.26	0.66	20	-1.2	5	25
natural killer cell activation	-0.007	0.008	-10000	0	-0.042	2	2
JAK2	0.057	0.072	0.19	6	-0.35	9	15
PIK3R1	0.019	0.036	-10000	0	-0.35	5	5
NFKB1	0.026	0.018	-10000	0	-0.35	1	1
RELA	0.026	0.008	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.19	0.23	0.66	8	-1.1	4	12
ALOX12B	0.19	0.23	0.66	8	-1.1	4	12
CXCL1	0.2	0.28	0.68	16	-1.1	12	28
T cell proliferation	0.21	0.26	0.66	20	-1.2	5	25
NFKBIA	0.026	0.008	-10000	0	-10000	0	0
IL17A	0.15	0.17	0.44	42	-0.55	4	46
PI3K	0.16	0.23	0.58	3	-1.1	5	8
IFNG	0.027	0.038	0.11	49	-0.11	2	51
STAT3 (dimer)	0.16	0.22	0.56	3	-1	5	8
IL18R1	0.021	0.032	-10000	0	-0.35	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.17	0.2	0.53	28	-0.75	5	33
IL18/IL18R	0.048	0.049	0.26	10	-0.21	8	18
macrophage activation	0.012	0.017	0.041	65	-0.044	4	69
TNF	0.2	0.25	0.68	13	-1.3	4	17
STAT3/STAT4	0.18	0.23	0.6	5	-1.1	5	10
STAT4 (dimer)	0.19	0.24	0.62	6	-1.2	5	11
IL18	0.027	0.034	0.29	9	-10000	0	9
IL19	0.23	0.25	0.68	18	-1.1	4	22
STAT5A (dimer)	0.18	0.24	0.61	7	-1.2	5	12
STAT1	0.024	0.016	0.28	2	-10000	0	2
SOCS3	0.021	0.023	-10000	0	-0.35	2	2
CXCL9	0.2	0.27	0.68	13	-1.2	8	21
MPO	0.2	0.24	0.68	8	-1.1	4	12
positive regulation of humoral immune response	0.21	0.26	0.66	20	-1.2	5	25
IL23/IL23R/JAK2/TYK2	0.21	0.26	0.68	16	-1.2	5	21
IL6	0.18	0.29	0.65	11	-1.1	17	28
STAT5A	0.021	0.017	-10000	0	-0.35	1	1
IL2	0.009	0.055	0.28	17	-10000	0	17
positive regulation of tyrosine phosphorylation of STAT protein	-0.007	0.008	-10000	0	-0.042	2	2
CD3E	0.18	0.27	0.66	9	-1.1	12	21
keratinocyte proliferation	0.21	0.26	0.66	20	-1.2	5	25
NOS2	0.18	0.27	0.66	9	-1	12	21

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.13	0.13	0.29	217	-10000	0	217
mol:Halofuginone	0.002	0	-10000	0	-10000	0	0
ITGA1	0.021	0.023	-10000	0	-0.35	2	2
CDKN1A	0.002	0.042	-10000	0	-0.31	6	6
PRL-3/alpha Tubulin	0.031	0.011	-10000	0	-10000	0	0
mol:Ca2+	-0.036	0.075	0.15	7	-0.25	53	60
AGT	-0.022	0.13	0.29	8	-0.35	65	73
CCNA2	-0.021	0.057	0.21	6	-10000	0	6
TUBA1B	0.023	0.002	-10000	0	-10000	0	0
EGR1	-0.022	0.082	-10000	0	-0.24	68	68
CDK2/Cyclin E1	0.091	0.1	0.29	19	-0.27	9	28
MAPK3	-0.01	0.004	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.033	0.006	-10000	0	-10000	0	0
MAPK1	-0.01	0.004	-10000	0	-10000	0	0
PTP4A1	-0.027	0.056	-10000	0	-10000	0	0
PTP4A3	0.021	0.007	-10000	0	-10000	0	0
PTP4A2	0.023	0.004	-10000	0	-10000	0	0
ITGB1	-0.01	0.004	-10000	0	-10000	0	0
SRC	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.001	0.046	-10000	0	-0.33	7	7
Rab GGTase beta/Rab GGTase alpha	0.033	0.007	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.001	0.071	0.35	1	-10000	0	1
RABGGTA	0.022	0.004	-10000	0	-10000	0	0
BCAR1	-0.016	0.008	-10000	0	-10000	0	0
RHOC	0.002	0.04	-10000	0	-0.35	4	4
RHOA	-0.001	0.052	-10000	0	-0.34	9	9
cell motility	0.012	0.06	0.34	1	-0.35	5	6
PRL-1/alpha Tubulin	-0.001	0.071	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.03	0.017	-10000	0	-0.25	1	1
ROCK1	0.012	0.06	0.34	1	-0.35	5	6
RABGGTB	0.023	0.002	-10000	0	-10000	0	0
CDK2	0.023	0.004	-10000	0	-10000	0	0
mitosis	-0.027	0.055	-10000	0	-10000	0	0
ATF5	0.024	0.022	0.28	4	-10000	0	4

×

Caspase cascade in apoptosis

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
TOP1	0.009	0.091	0.22	1	-0.41	16	17
ACTA1	0.012	0.066	0.21	8	-0.26	10	18
NUMA1	0.008	0.094	0.22	1	-0.41	17	18
SPTAN1	0.002	0.062	0.22	3	-0.27	10	13
LIMK1	0.004	0.069	0.24	12	-0.26	12	24
BIRC3	0.018	0.045	0.28	2	-0.35	7	9
BIRC2	0.022	0.004	-10000	0	-10000	0	0
BAX	0.023	0.004	-10000	0	-10000	0	0
CASP10	-0.008	0.04	0.26	3	-0.27	6	9
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.023	0.001	-10000	0	-10000	0	0
PTK2	0.009	0.09	0.22	1	-0.4	16	17
DIABLO	0.023	0.003	-10000	0	-10000	0	0
apoptotic nuclear changes	0.002	0.062	0.22	3	-0.27	10	13
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.023	0.002	-10000	0	-10000	0	0
GSN	0	0.062	0.21	3	-0.27	11	14
MADD	0.022	0.005	-10000	0	-10000	0	0
TFAP2A	0.15	0.12	0.33	50	-0.62	6	56
BID	0.004	0.023	0.16	3	-0.17	5	8
MAP3K1	-0.008	0.1	-10000	0	-0.41	28	28
TRADD	0.02	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.033	0.007	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.002	0.067	0.23	8	-0.26	12	20
CASP9	0.022	0.005	-10000	0	-10000	0	0
DNA repair	-0.015	0.044	0.26	4	-0.16	3	7
neuron apoptosis	0.008	0.11	-10000	0	-0.83	8	8
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.004	0.087	0.22	2	-0.41	13	15
APAF1	0.023	0.002	-10000	0	-10000	0	0
CASP6	-0.004	0.17	-10000	0	-0.88	17	17
TRAF2	0.022	0.006	-10000	0	-10000	0	0
ICAD/CAD	0	0.064	0.26	6	-0.33	5	11
CASP7	-0.002	0.058	0.25	6	-0.25	5	11
KRT18	0.018	0.057	-10000	0	-0.64	2	2
apoptosis	0.003	0.11	0.4	12	-0.42	18	30
DFFA	0.003	0.065	0.25	6	-0.27	10	16
DFFB	0.001	0.062	0.2	4	-0.27	11	15
PARP1	0.015	0.044	0.16	3	-0.27	4	7
actin filament polymerization	-0.002	0.072	0.28	6	-0.28	13	19
TNF	0.053	0.088	0.28	66	-0.35	2	68
CYCS	0.007	0.042	0.16	10	-0.2	8	18
SATB1	-0.027	0.17	0.33	1	-0.83	18	19
SLK	0.004	0.072	0.31	10	-0.27	10	20
p15 BID/BAX	0.015	0.042	-10000	0	-0.17	8	8
CASP2	0.012	0.055	0.21	9	-0.29	6	15
JNK cascade	0.007	0.1	0.41	28	-10000	0	28
CASP3	0.004	0.066	0.21	5	-0.28	12	17
LMNB2	-0.014	0.16	0.28	2	-0.47	45	47
RIPK1	0.022	0.004	-10000	0	-10000	0	0
CASP4	0.022	0.017	-10000	0	-0.35	1	1
Mammalian IAPs/DIABLO	0.054	0.033	0.21	2	-0.19	7	9
negative regulation of DNA binding	0.15	0.11	0.33	51	-0.61	6	57
stress fiber formation	0.004	0.072	0.31	10	-0.28	9	19
GZMB	-0.001	0.05	0.12	51	-0.29	5	56
CASP1	0.009	0.02	-10000	0	-0.26	3	3
LMNB1	0.006	0.12	0.27	3	-0.5	20	23
APP	0.008	0.11	-10000	0	-0.85	8	8
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.006	0.001	-10000	0	-10000	0	0
VIM	0.002	0.1	0.31	10	-0.43	18	28
LMNA	0.01	0.085	0.27	2	-0.36	17	19
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.014	0.058	0.22	3	-0.32	6	9
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	0.004	0.064	0.2	6	-0.34	5	11
APAF-1/Caspase 9	0.007	0.097	-10000	0	-0.64	11	11
nuclear fragmentation during apoptosis	0.009	0.092	0.22	1	-0.4	17	18
CFL2	0.002	0.072	0.28	13	-0.27	7	20
GAS2	-0.01	0.075	0.21	3	-0.28	15	18
positive regulation of apoptosis	0.001	0.13	0.24	5	-0.49	25	30
PRF1	0.022	0.036	0.28	4	-0.35	3	7

×

ErbB4 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
ErbB4/ErbB4/HBEGF/HBEGF	0.027	0.054	-10000	0	-10000	0	0
epithelial cell differentiation	-0.01	0.09	0.24	1	-0.31	6	7
ITCH	0.016	0.024	-10000	0	-10000	0	0
WWP1	0.019	0.056	0.31	2	-10000	0	2
FYN	0.023	0.004	-10000	0	-10000	0	0
EGFR	0.014	0.059	0.33	1	-0.35	13	14
PRL	0.012	0.07	0.28	5	-0.35	17	22
neuron projection morphogenesis	0.035	0.094	0.26	34	-10000	0	34
PTPRZ1	0.035	0.062	0.28	32	-10000	0	32
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.028	0.051	-10000	0	-0.24	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.008	0.042	-10000	0	-0.27	2	2
ADAM17	0.016	0.024	-10000	0	-10000	0	0
ErbB4/ErbB4	0.017	0.05	0.23	2	-10000	0	2
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.031	0.066	0.25	11	-10000	0	11
NCOR1	0.021	0.007	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.017	0.046	-10000	0	-0.25	2	2
GRIN2B	0.016	0.063	0.24	17	-0.24	2	19
ErbB4/ErbB2/betacellulin	0.022	0.06	0.25	7	-0.22	1	8
STAT1	0.024	0.016	0.28	2	-10000	0	2
HBEGF	0.023	0.004	-10000	0	-10000	0	0
PRLR	-0.05	0.15	-10000	0	-0.35	104	104
E4ICDs/ETO2	0.006	0.077	-10000	0	-0.29	6	6
axon guidance	0.012	0.049	0.24	1	-10000	0	1
NEDD4	-0.014	0.094	-10000	0	-0.35	37	37
Prolactin receptor/Prolactin receptor/Prolactin	-0.028	0.12	0.21	4	-0.25	114	118
CBFA2T3	-0.025	0.12	-10000	0	-0.35	65	65
ErbB4/ErbB2/HBEGF	0.028	0.05	0.25	7	-10000	0	7
MAPK3	0.03	0.083	0.25	17	-10000	0	17
STAT1 (dimer)	0.026	0.055	0.25	1	-10000	0	1
MAPK1	0.03	0.084	0.25	18	-10000	0	18
JAK2	0.016	0.048	-10000	0	-0.35	9	9
ErbB4/ErbB2/neuregulin 1 beta	0.011	0.051	0.23	11	-0.25	2	13
NRG1	-0.012	0.034	-10000	0	-0.25	9	9
NRG3	0.03	0.052	0.29	21	-10000	0	21
NRG2	-0.03	0.13	-10000	0	-0.35	75	75
NRG4	0.045	0.073	0.28	47	-10000	0	47
heart development	0.012	0.049	0.24	1	-10000	0	1
neural crest cell migration	0.011	0.051	0.23	11	-0.25	2	13
ERBB2	0.001	0.051	0.3	14	-10000	0	14
WWOX/E4ICDs	0.025	0.05	-10000	0	-10000	0	0
SHC1	0.019	0.009	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.043	0.078	0.34	2	-0.28	2	4
apoptosis	-0.033	0.061	0.31	2	-0.27	2	4
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.004	0.083	-10000	0	-0.29	10	10
ErbB4/ErbB2/epiregulin	0.049	0.082	0.31	16	-10000	0	16
ErbB4/ErbB4/betacellulin/betacellulin	0.02	0.065	-10000	0	-0.24	4	4
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.005	0.11	0.28	1	-0.29	23	24
MDM2	0.013	0.048	0.26	3	-10000	0	3
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.015	0.037	-10000	0	-0.23	2	2
STAT5A	0.01	0.052	0.28	1	-10000	0	1
ErbB4/EGFR/neuregulin 1 beta	0.014	0.057	0.31	1	-0.29	6	7
DLG4	0.02	0.023	-10000	0	-0.35	2	2
GRB2/SHC	0.026	0.015	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.022	0.048	-10000	0	-10000	0	0
STAT5A (dimer)	-0.003	0.1	0.29	1	-0.34	5	6
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.024	0.058	-10000	0	-0.27	2	2
LRIG1	0.02	0.028	-10000	0	-0.35	3	3
EREG	0.054	0.086	0.28	68	-10000	0	68
BTC	0.011	0.065	-10000	0	-0.35	17	17
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.009	0.041	0.23	1	-10000	0	1
ERBB4	0.017	0.05	0.23	2	-10000	0	2
STAT5B	0.02	0.023	-10000	0	-0.35	2	2
YAP1	0.013	0.073	-10000	0	-0.47	10	10
GRB2	0.022	0.006	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.042	0.073	0.32	14	-10000	0	14
glial cell differentiation	-0.022	0.047	-10000	0	-10000	0	0
WWOX	0.02	0.008	-10000	0	-10000	0	0
cell proliferation	0.014	0.088	0.28	11	-0.36	3	14

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.023	0.004	-10000	0	-10000	0	0
SPHK1	0.024	0.022	0.31	3	-10000	0	3
GNAI2	0.022	0.005	-10000	0	-10000	0	0
mol:S1P	0.01	0.01	0.21	1	-10000	0	1
GNAO1	-0.065	0.16	-10000	0	-0.35	124	124
mol:Sphinganine-1-P	-0.01	0.02	0.23	3	-10000	0	3
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.041	0.038	-10000	0	-0.19	5	5
GNAI3	0.023	0.002	-10000	0	-10000	0	0
G12/G13	0.031	0.01	-10000	0	-10000	0	0
S1PR3	0.01	0.065	-10000	0	-0.35	17	17
S1PR2	0.022	0.006	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.001	0.03	0.14	1	-0.22	5	6
S1PR5	0.025	0.053	0.29	13	-0.35	4	17
S1PR4	0.02	0.026	0.28	1	-0.35	2	3
GNAI1	0.017	0.045	-10000	0	-0.35	8	8
S1P/S1P5/G12	0.034	0.044	0.2	8	-0.19	8	16
S1P/S1P3/Gq	-0.014	0.11	-10000	0	-0.31	53	53
S1P/S1P4/Gi	-0.038	0.11	-10000	0	-0.35	29	29
GNAQ	0.021	0.017	-10000	0	-0.35	1	1
GNAZ	0.01	0.065	-10000	0	-0.35	17	17
GNA14	-0.01	0.1	-10000	0	-0.35	45	45
GNA15	0.025	0.03	0.28	7	-10000	0	7
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
GNA11	0.014	0.051	-10000	0	-0.35	10	10
ABCC1	0.022	0.005	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.017	0.002	-10000	0	-10000	0	0
PRKCZ	0.022	0.02	0.28	1	-0.35	1	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.022	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.012	0.041	-10000	0	-0.22	12	12
IRAK/TOLLIP	0.023	0.007	-10000	0	-10000	0	0
IKBKB	0.021	0.007	-10000	0	-10000	0	0
IKBKG	0.023	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.053	0.07	0.23	62	-0.25	4	66
IL1A	0.038	0.063	0.28	34	-10000	0	34
IL1B	-0.014	0.028	-10000	0	-0.29	5	5
IRAK/TRAF6/p62/Atypical PKCs	0.046	0.025	-10000	0	-0.17	1	1
IL1R2	0.036	0.071	0.28	34	-0.35	4	38
IL1R1	0.017	0.048	-10000	0	-0.35	9	9
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.01	0.059	0.22	2	-0.24	14	16
TOLLIP	0.022	0.005	-10000	0	-10000	0	0
TICAM2	0.017	0.045	-10000	0	-0.35	8	8
MAP3K3	0.022	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.016	0.002	-10000	0	-10000	0	0
IKK complex/ELKS	0.017	0.049	0.23	1	-0.32	1	2
JUN	-0.01	0.041	0.17	15	-0.18	9	24
MAP3K7	0.023	0.003	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.042	0.053	-10000	0	-0.22	13	13
IL1 alpha/IL1R1/IL1RAP/MYD88	0.056	0.055	0.21	31	-0.21	9	40
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.063	0.055	-10000	0	-0.2	9	9
IL1 beta fragment/IL1R1/IL1RAP	0.025	0.042	-10000	0	-0.21	14	14
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
MAPK8	-0.002	0.042	0.19	14	-0.16	4	18
IRAK1	0.01	0.002	-10000	0	-10000	0	0
IL1RN/IL1R1	0.053	0.073	0.21	74	-0.24	9	83
IRAK4	0.023	0.003	-10000	0	-10000	0	0
PRKCI	0.021	0.007	-10000	0	-10000	0	0
TRAF6	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.027	0.029	-10000	0	-0.25	5	5
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.013	0.052	-10000	0	-0.27	9	9
CHUK	0.022	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.025	0.042	-10000	0	-0.21	14	14
IL1 beta/IL1R2	0.038	0.059	0.2	45	-0.23	9	54
IRAK/TRAF6/TAK1/TAB1/TAB2	0.03	0.009	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.03	0.048	-10000	0	-0.36	3	3
IRAK3	0.007	0.076	-10000	0	-0.35	23	23
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.042	0.055	-10000	0	-0.2	19	19
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.017	0.044	-10000	0	-0.23	8	8
IL1 alpha/IL1R1/IL1RAP	0.046	0.055	0.2	31	-0.23	9	40
RELA	0.022	0.004	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.022	0.004	-10000	0	-10000	0	0
MYD88	0.022	0.004	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.035	0.013	-10000	0	-10000	0	0
IL1RAP	0.019	0.028	-10000	0	-0.35	3	3
UBE2N	0.023	0.002	-10000	0	-10000	0	0
IRAK/TRAF6	0.017	0.043	-10000	0	-0.3	3	3
CASP1	0.021	0.023	-10000	0	-0.35	2	2
IL1RN/IL1R2	0.067	0.083	0.23	99	-0.24	3	102
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.036	0.044	-10000	0	-0.2	14	14
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.012	0.057	-10000	0	-0.28	13	13
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
IL1RN	0.059	0.092	0.28	76	-10000	0	76
TRAF6/TAK1/TAB1/TAB2	0.032	0.008	-10000	0	-10000	0	0
MAP2K6	0.012	0.061	0.16	73	-10000	0	73

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.008	0.084	0.27	2	-0.39	12	14
BAG4	0.019	0.024	-10000	0	-0.35	2	2
BAD	0.005	0.043	0.18	10	-0.16	7	17
NFKBIA	0.022	0.004	-10000	0	-10000	0	0
BIRC3	0.018	0.045	0.28	2	-0.35	7	9
BAX	0.004	0.041	0.17	7	-0.15	9	16
EnzymeConsortium:3.1.4.12	0.003	0.024	0.073	7	-0.085	15	22
IKBKB	0.018	0.097	0.28	19	-0.38	9	28
MAP2K2	0.002	0.042	0.22	7	-0.16	3	10
MAP2K1	0.002	0.042	0.21	8	-0.17	4	12
SMPD1	0.001	0.033	-10000	0	-0.14	16	16
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.015	0.086	0.27	4	-0.36	14	18
MAP2K4	0.003	0.035	0.23	3	-0.17	3	6
protein ubiquitination	0.012	0.09	0.35	3	-0.39	10	13
EnzymeConsortium:2.7.1.37	0.001	0.047	0.22	9	-0.18	3	12
response to UV	0	0	0.002	9	-0.002	1	10
RAF1	0.003	0.045	0.21	9	-0.16	7	16
CRADD	0.023	0.002	-10000	0	-10000	0	0
mol:ceramide	0.005	0.038	0.11	9	-0.14	15	24
I-kappa-B-alpha/RELA/p50/ubiquitin	0.03	0.008	-10000	0	-10000	0	0
MADD	0.022	0.005	-10000	0	-10000	0	0
MAP3K1	0.004	0.038	0.19	5	-0.15	8	13
TRADD	0.02	0.008	-10000	0	-10000	0	0
RELA/p50	0.022	0.004	-10000	0	-10000	0	0
MAPK3	0.002	0.048	0.21	9	-0.18	5	14
MAPK1	0	0.052	0.2	9	-0.22	7	16
p50/RELA/I-kappa-B-alpha	0.032	0.008	-10000	0	-10000	0	0
FADD	0.009	0.081	0.23	2	-0.38	12	14
KSR1	0.004	0.04	0.18	6	-0.15	10	16
MAPK8	0.001	0.041	0.19	8	-0.16	2	10
TRAF2	0.022	0.006	-10000	0	-10000	0	0
response to radiation	0	0	0.002	4	-10000	0	4
CHUK	0.007	0.084	0.3	3	-0.38	11	14
TNF R/SODD	0.029	0.021	-10000	0	-0.25	2	2
TNF	0.053	0.088	0.28	66	-0.35	2	68
CYCS	0.013	0.049	0.16	18	-0.16	6	24
IKBKG	0.006	0.085	0.3	5	-0.39	10	15
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.011	0.085	-10000	0	-0.42	11	11
RELA	0.022	0.004	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
AIFM1	0.012	0.046	0.15	14	-0.16	5	19
TNF/TNF R/SODD	0.054	0.054	0.2	51	-0.21	2	53
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
response to heat	0	0	0.002	4	-10000	0	4
CASP8	0.018	0.08	-10000	0	-0.59	8	8
NSMAF	0.018	0.09	0.26	13	-0.41	9	22
response to hydrogen peroxide	0	0	0.002	9	-0.002	1	10
BCL2	-0.008	0.1	-10000	0	-0.35	44	44

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.014	0.015	-10000	0	-0.27	1	1
CRKL	0.022	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
DOCK1	0.017	0.042	-10000	0	-0.35	7	7
ITGA4	0.022	0.025	0.28	1	-0.35	2	3
alpha4/beta7 Integrin/MAdCAM1	0.063	0.047	0.21	41	-0.19	1	42
EPO	0.01	0.064	0.28	1	-0.35	16	17
alpha4/beta7 Integrin	0.034	0.017	0.21	2	-0.25	1	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.032	0.02	0.21	1	-0.25	2	3
EPO/EPOR (dimer)	0.025	0.054	0.23	8	-0.25	16	24
lamellipodium assembly	0.013	0.074	-10000	0	-0.42	8	8
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
PI3K	0.027	0.029	-10000	0	-0.25	5	5
ARF6	0.023	0.003	-10000	0	-10000	0	0
JAK2	0.008	0.052	0.17	4	-0.22	24	28
PXN	0.023	0.003	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
MADCAM1	0.04	0.069	0.28	41	-10000	0	41
cell adhesion	0.061	0.046	0.2	41	-0.19	1	42
CRKL/CBL	0.032	0.01	-10000	0	-10000	0	0
ITGB1	0.022	0.004	-10000	0	-10000	0	0
SRC	-0.021	0.056	0.18	14	-0.2	33	47
ITGB7	0.023	0.011	0.28	1	-10000	0	1
RAC1	0.022	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.027	0.068	0.2	1	-0.22	36	37
p130Cas/Crk/Dock1	0.008	0.056	-10000	0	-0.38	2	2
VCAM1	-0.004	0.097	-10000	0	-0.35	39	39
RHOA	0.022	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.053	0.024	0.21	1	-0.19	2	3
BCAR1	-0.02	0.049	0.18	12	-0.19	26	38
EPOR	0.026	0.034	0.31	7	-10000	0	7
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.022	0.005	-10000	0	-10000	0	0
GIT1	0.022	0.005	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.076	-10000	0	-0.46	7	7

×

IL27-mediated signaling 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
TGFB1	0.023	0.017	-10000	0	-0.35	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.013	0.11	0.42	11	-0.37	1	12
IL27/IL27R/JAK1	0.025	0.12	0.47	4	-0.95	2	6
TBX21	-0.017	0.11	0.35	4	-0.4	9	13
IL12B	0.023	0.013	0.28	1	-10000	0	1
IL12A	-0.003	0.029	0.12	11	-0.24	4	15
IL6ST	-0.033	0.13	-10000	0	-0.35	79	79
IL27RA/JAK1	0.018	0.084	-10000	0	-1	2	2
IL27	0.025	0.043	0.29	12	-10000	0	12
TYK2	0.022	0.014	-10000	0	-10000	0	0
T-helper cell lineage commitment	0.007	0.065	0.44	2	-10000	0	2
T-helper 2 cell differentiation	0.013	0.11	0.42	11	-0.37	1	12
T cell proliferation during immune response	0.013	0.11	0.42	11	-0.37	1	12
MAPKKK cascade	-0.013	0.11	0.37	1	-0.42	11	12
STAT3	0.022	0.006	-10000	0	-10000	0	0
STAT2	0.023	0.003	-10000	0	-10000	0	0
STAT1	0.024	0.016	0.28	2	-10000	0	2
IL12RB1	0.026	0.053	0.29	13	-0.35	4	17
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.008	0.11	0.36	8	-0.51	3	11
IL27/IL27R/JAK2/TYK2	-0.012	0.11	0.37	1	-0.44	9	10
positive regulation of T cell mediated cytotoxicity	-0.013	0.11	0.37	1	-0.42	11	12
STAT1 (dimer)	0.017	0.14	0.59	5	-0.72	3	8
JAK2	0.017	0.049	-10000	0	-0.35	9	9
JAK1	0.022	0.016	-10000	0	-0.35	1	1
STAT2 (dimer)	-0.005	0.12	0.34	1	-0.4	11	12
T cell proliferation	-0.019	0.11	0.35	1	-0.39	16	17
IL12/IL12R/TYK2/JAK2	0.006	0.17	-10000	0	-0.71	25	25
IL17A	0.006	0.063	0.44	2	-10000	0	2
mast cell activation	0.013	0.11	0.42	11	-0.37	1	12
IFNG	0.007	0.034	0.11	9	-0.098	7	16
T cell differentiation	-0.001	0.005	0.013	3	-0.018	12	15
STAT3 (dimer)	-0.005	0.12	0.34	1	-0.39	14	15
STAT5A (dimer)	-0.005	0.12	0.34	1	-0.39	14	15
STAT4 (dimer)	-0.007	0.12	0.34	1	-0.4	13	14
STAT4	0.022	0.016	-10000	0	-0.35	1	1
T cell activation	-0.005	0.01	0.12	2	-0.087	2	4
IL27R/JAK2/TYK2	0.007	0.11	-10000	0	-0.77	3	3
GATA3	0.001	0.16	0.58	14	-1.1	6	20
IL18	-0.002	0.015	0.11	9	-10000	0	9
positive regulation of mast cell cytokine production	-0.004	0.12	0.33	1	-0.38	14	15
IL27/EBI3	0.038	0.048	0.25	20	-10000	0	20
IL27RA	0.005	0.084	-10000	0	-1.1	2	2
IL6	0.017	0.069	0.28	9	-0.35	14	23
STAT5A	0.021	0.017	-10000	0	-0.35	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.007	0.038	0.43	2	-10000	0	2
IL1B	-0.006	0.021	-10000	0	-0.24	4	4
EBI3	0.027	0.043	0.29	13	-10000	0	13
TNF	0.009	0.043	0.11	66	-0.24	2	68

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.013	0.025	-10000	0	-0.18	8	8
epithelial cell differentiation	0.042	0.022	-10000	0	-0.17	2	2
CYFIP2	0.021	0.028	-10000	0	-0.35	3	3
ENAH	-0.006	0.056	0.27	12	-10000	0	12
EGFR	0.014	0.059	0.33	1	-0.35	13	14
EPHA2	0.022	0.005	-10000	0	-10000	0	0
MYO6	-0.012	0.025	0.17	7	-10000	0	7
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.043	0.017	-10000	0	-0.21	1	1
AQP5	0.077	0.088	0.28	2	-0.41	5	7
CTNND1	0.023	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.013	0.018	0.17	3	-10000	0	3
regulation of calcium-dependent cell-cell adhesion	-0.016	0.037	0.17	7	-0.3	1	8
EGF	0.031	0.055	0.28	21	-0.35	2	23
NCKAP1	0.023	0.003	-10000	0	-10000	0	0
AQP3	-0.001	0.057	-10000	0	-0.34	8	8
cortical microtubule organization	0.042	0.022	-10000	0	-0.17	2	2
GO:0000145	-0.013	0.017	0.16	3	-10000	0	3
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.046	0.024	-10000	0	-0.17	2	2
MLLT4	0.022	0.005	-10000	0	-10000	0	0
ARF6/GDP	-0.02	0.018	-10000	0	-0.17	3	3
ARF6	0.023	0.003	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.043	0.031	0.21	1	-0.19	2	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.004	0.016	0.16	3	-10000	0	3
PVRL2	0.022	0.005	-10000	0	-10000	0	0
ZYX	-0.012	0.024	0.17	6	-10000	0	6
ARF6/GTP	0.047	0.033	-10000	0	-0.18	2	2
CDH1	0.019	0.024	-10000	0	-0.35	2	2
EGFR/EGFR/EGF/EGF	0.033	0.044	-10000	0	-0.18	14	14
RhoA/GDP	0.042	0.023	-10000	0	-0.16	2	2
actin cytoskeleton organization	-0.014	0.022	0.16	6	-10000	0	6
IGF-1R heterotetramer	0.009	0.069	-10000	0	-0.35	19	19
GIT1	0.022	0.005	-10000	0	-10000	0	0
IGF1R	0.009	0.069	-10000	0	-0.35	19	19
IGF1	-0.046	0.14	-10000	0	-0.35	100	100
DIAPH1	0.018	0.096	-10000	0	-0.5	11	11
Wnt receptor signaling pathway	-0.042	0.022	0.17	2	-10000	0	2
RHOA	0.022	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.02	0.018	-10000	0	-0.17	3	3
CTNNA1	0.023	0.004	-10000	0	-10000	0	0
VCL	-0.014	0.022	0.16	6	-10000	0	6
EFNA1	0.02	0.02	0.3	2	-10000	0	2
LPP	-0.014	0.023	0.17	6	-10000	0	6
Ephrin A1/EPHA2	0.03	0.025	-10000	0	-0.16	2	2
SEC6/SEC8	-0.02	0.012	-10000	0	-10000	0	0
MGAT3	-0.016	0.037	0.17	7	-0.31	1	8
HGF/MET	-0.003	0.088	-10000	0	-0.18	96	96
HGF	-0.05	0.15	-10000	0	-0.35	104	104
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.013	0.025	-10000	0	-0.18	8	8
actin cable formation	0.046	0.1	0.23	95	-0.24	2	97
KIAA1543	-0.013	0.023	0.16	6	-0.17	2	8
KIFC3	-0.013	0.023	0.17	6	-10000	0	6
NCK1	0.021	0.023	-10000	0	-0.35	2	2
EXOC3	0.022	0.006	-10000	0	-10000	0	0
ACTN1	-0.012	0.025	0.17	7	-10000	0	7
NCK1/GIT1	0.03	0.019	-10000	0	-0.25	2	2
mol:GDP	0.042	0.022	-10000	0	-0.17	2	2
EXOC4	0.022	0.005	-10000	0	-10000	0	0
STX4	-0.012	0.025	0.17	7	-10000	0	7
PIP5K1C	-0.013	0.019	0.17	3	-10000	0	3
LIMA1	0.023	0.003	-10000	0	-10000	0	0
ABI1	0.022	0.005	-10000	0	-10000	0	0
ROCK1	0.018	0.086	0.32	16	-10000	0	16
adherens junction assembly	-0.044	0.14	0.2	1	-0.55	31	32
IGF-1R heterotetramer/IGF1	-0.007	0.092	-10000	0	-0.18	107	107
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.031	0.01	-10000	0	-10000	0	0
MET	0.021	0.042	0.28	4	-0.35	5	9
PLEKHA7	-0.013	0.025	0.17	6	-0.17	1	7
mol:GTP	0.042	0.03	0.2	1	-0.19	2	3
establishment of epithelial cell apical/basal polarity	0.001	0.077	0.35	13	-10000	0	13
cortical actin cytoskeleton stabilization	0.013	0.025	-10000	0	-0.18	8	8
regulation of cell-cell adhesion	-0.014	0.022	0.16	6	-10000	0	6
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.013	0.025	-10000	0	-0.18	8	8

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.005	0.061	0.2	2	-0.24	14	16
adherens junction organization	-0.007	0.089	0.29	1	-0.37	22	23
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.062	0.21	2	-0.26	3	5
FMN1	-0.002	0.076	-10000	0	-0.32	21	21
mol:IP3	0.001	0.042	-10000	0	-0.21	7	7
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.002	0.086	-10000	0	-0.31	28	28
CTNNB1	0.023	0.006	-10000	0	-10000	0	0
AKT1	0	0.052	-10000	0	-0.24	9	9
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.005	0.12	-10000	0	-0.7	10	10
CTNND1	0.024	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.007	0.072	-10000	0	-0.31	21	21
VASP	-0.006	0.079	-10000	0	-0.3	26	26
ZYX	-0.006	0.078	-10000	0	-0.3	26	26
JUB	-0.004	0.081	-10000	0	-0.29	28	28
EGFR(dimer)	0.002	0.094	0.26	1	-0.3	31	32
E-cadherin/beta catenin-gamma catenin	0.038	0.026	-10000	0	-0.28	2	2
mol:PI-3-4-5-P3	0.015	0.062	-10000	0	-0.24	11	11
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
PI3K	0.015	0.063	-10000	0	-0.25	10	10
FYN	0.005	0.053	0.18	4	-0.29	4	8
mol:Ca2+	0.001	0.042	-10000	0	-0.21	7	7
JUP	0.022	0.017	-10000	0	-0.34	1	1
PIK3R1	0.02	0.036	-10000	0	-0.35	5	5
mol:DAG	0.001	0.042	-10000	0	-0.21	7	7
CDH1	0.019	0.024	-10000	0	-0.35	2	2
RhoA/GDP	0.013	0.063	0.21	1	-0.32	3	4
establishment of polarity of embryonic epithelium	-0.007	0.08	-10000	0	-0.3	27	27
SRC	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
EGFR	0.014	0.059	0.33	1	-0.35	13	14
CASR	0.002	0.054	0.21	6	-0.21	6	12
RhoA/GTP	0.018	0.052	-10000	0	-0.23	3	3
AKT2	0	0.052	-10000	0	-0.25	9	9
actin cable formation	-0.002	0.073	0.2	8	-0.32	17	25
apoptosis	-0.009	0.072	0.24	18	-0.24	10	28
CTNNA1	0.023	0.006	-10000	0	-10000	0	0
mol:GDP	0	0.059	-10000	0	-0.25	8	8
PIP5K1A	-0.006	0.072	-10000	0	-0.31	20	20
PLCG1	0.001	0.043	-10000	0	-0.22	7	7
Rac1/GTP	0.01	0.09	0.24	1	-0.3	24	25
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.021	0.006	-10000	0	-10000	0	0
HDAC4	0.023	0.004	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.008	0.034	0.25	2	-0.23	7	9
CDKN1A	-0.008	0.007	-10000	0	-10000	0	0
KAT2B	0.017	0.045	-10000	0	-0.35	8	8
BAX	0.023	0.004	-10000	0	-10000	0	0
FOXO3	-0.003	0.006	-10000	0	-10000	0	0
FOXO1	0.021	0.023	-10000	0	-0.35	2	2
FOXO4	0.009	0.015	-10000	0	-0.22	2	2
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.022	0.006	-10000	0	-10000	0	0
TAT	0.019	0.013	0.28	1	-10000	0	1
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.005	0.05	0.12	45	-0.24	8	53
PPARGC1A	-0.054	0.15	0.28	2	-0.35	111	113
FHL2	0.02	0.036	-10000	0	-0.35	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.029	0.019	-10000	0	-0.25	2	2
HIST2H4A	-0.008	0.034	0.23	7	-0.25	2	9
SIRT1/FOXO3a	0.016	0.033	-10000	0	-0.2	7	7
SIRT1	0.019	0.023	-10000	0	-0.35	2	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.035	0.024	-10000	0	-0.21	2	2
SIRT1/Histone H1b	0.016	0.05	-10000	0	-0.22	12	12
apoptosis	-0.039	0.021	0.21	2	-10000	0	2
SIRT1/PGC1A	-0.021	0.096	0.19	2	-0.21	112	114
p53/SIRT1	0.025	0.019	-10000	0	-0.25	2	2
SIRT1/FOXO4	0.011	0.048	-10000	0	-0.2	15	15
FOXO1/FHL2/SIRT1	0.036	0.03	-10000	0	-0.19	8	8
HIST1H1E	0.014	0.022	0.21	2	-10000	0	2
SIRT1/p300	0.029	0.02	-10000	0	-0.25	2	2
muscle cell differentiation	-0.022	0.037	0.22	9	-0.21	2	11
TP53	0.02	0.016	0.35	1	-10000	0	1
KU70/SIRT1/BAX	0.04	0.021	-10000	0	-0.21	2	2
CREBBP	0.022	0.005	-10000	0	-10000	0	0
MEF2D	0.019	0.009	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.027	0.022	0.21	1	-0.25	2	3
ACSS2	-0.013	0.015	-10000	0	-0.25	2	2
SIRT1/PCAF/MYOD	0.022	0.037	0.21	2	-0.23	9	11

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.015	0.091	-10000	0	-0.27	57	57
KLHL20	-0.004	0.062	0.2	2	-0.2	29	31
CYFIP2	0.021	0.028	-10000	0	-0.35	3	3
Rac1/GDP	0.002	0.068	0.25	3	-0.27	7	10
ENAH	-0.018	0.092	-10000	0	-0.28	58	58
AP1M1	0.022	0.005	-10000	0	-10000	0	0
RAP1B	0.023	0.002	-10000	0	-10000	0	0
RAP1A	0.023	0.002	-10000	0	-10000	0	0
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
CDC42/GTP	0.014	0.028	-10000	0	-0.22	1	1
ABI1/Sra1/Nap1	-0.013	0.037	-10000	0	-0.14	32	32
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.049	0.028	-10000	0	-0.19	2	2
RAPGEF1	-0.011	0.079	0.22	2	-0.31	9	11
CTNND1	0.023	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.011	0.099	-10000	0	-0.28	63	63
CRK	-0.008	0.081	-10000	0	-0.27	40	40
E-cadherin/gamma catenin/alpha catenin	0.039	0.027	-10000	0	-0.29	2	2
alphaE/beta7 Integrin	0.032	0.013	0.21	1	-10000	0	1
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
NCKAP1	0.023	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.042	0.011	-10000	0	-10000	0	0
DLG1	-0.012	0.085	-10000	0	-0.28	49	49
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.016	0.016	-10000	0	-0.16	1	1
MLLT4	0.022	0.005	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.036	0.036	-10000	0	-0.18	12	12
PI3K	-0.019	0.02	-10000	0	-0.21	1	1
ARF6	0.023	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.028	0.027	-10000	0	-0.34	2	2
TIAM1	0.014	0.057	-10000	0	-0.35	13	13
E-cadherin(dimer)/Ca2+	0.046	0.024	-10000	0	-0.17	2	2
AKT1	-0.011	0.021	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
CDH1	0.019	0.024	-10000	0	-0.35	2	2
RhoA/GDP	0.001	0.067	0.23	1	-0.27	5	6
actin cytoskeleton organization	-0.002	0.047	0.16	4	-0.15	29	33
CDC42/GDP	0.003	0.068	0.25	3	-0.27	7	10
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.012	0.022	-10000	0	-0.32	2	2
ITGB7	0.023	0.011	0.28	1	-10000	0	1
RAC1	0.022	0.005	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.05	0.026	-10000	0	-0.18	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin	0.035	0.019	-10000	0	-0.17	2	2
mol:GDP	-0.01	0.073	0.25	3	-0.29	9	12
CDC42/GTP/IQGAP1	0.03	0.008	-10000	0	-10000	0	0
JUP	0.021	0.017	-10000	0	-0.35	1	1
p120 catenin/RhoA/GDP	0.009	0.069	0.24	1	-0.28	4	5
RAC1/GTP/IQGAP1	0.029	0.008	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.03	0.011	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
CDC42	0.022	0.005	-10000	0	-10000	0	0
CTNNA1	0.023	0.004	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.004	0.037	0.15	7	-0.1	13	20
NME1	0.022	0.006	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.009	0.083	-10000	0	-0.27	47	47
regulation of cell-cell adhesion	0.008	0.023	-10000	0	-0.19	1	1
WASF2	-0.001	0.025	-10000	0	-10000	0	0
Rap1/GTP	0.018	0.038	-10000	0	-0.24	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.056	0.034	-10000	0	-0.25	2	2
CCND1	0.004	0.043	0.17	7	-0.12	16	23
VAV2	-0.028	0.16	-10000	0	-0.57	34	34
RAP1/GDP	0.018	0.06	0.25	4	-0.26	4	8
adherens junction assembly	-0.01	0.083	-10000	0	-0.27	49	49
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.022	0.005	-10000	0	-10000	0	0
PIP5K1C	0.021	0.006	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.041	0.029	-10000	0	-0.24	2	2
E-cadherin/beta catenin	0.008	0.019	-10000	0	-0.29	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.015	0.091	-10000	0	-0.28	56	56
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
Rac1/GTP	-0.017	0.086	0.18	1	-0.31	31	32
E-cadherin/beta catenin/alpha catenin	0.039	0.022	-10000	0	-0.2	2	2
ITGAE	0.021	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.012	0.1	-10000	0	-0.29	63	63

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.022	0.043	0.35	4	-0.29	6	10
PI3K Class IB/PDE3B	0.022	0.043	0.29	6	-0.35	4	10
PDE3B	0.022	0.043	0.29	6	-0.35	4	10

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.024	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.015	0.092	0.26	6	-0.3	19	25
ERC1	0.022	0.004	-10000	0	-10000	0	0
RIP2/NOD2	0.029	0.019	0.21	1	-0.25	1	2
NFKBIA	-0.008	0.028	0.2	8	-10000	0	8
BIRC2	0.022	0.004	-10000	0	-10000	0	0
IKBKB	0.021	0.007	-10000	0	-10000	0	0
RIPK2	0.021	0.007	-10000	0	-10000	0	0
IKBKG	0.016	0.02	-10000	0	-10000	0	0
IKK complex/A20	0.033	0.11	0.26	3	-0.34	33	36
NEMO/A20/RIP2	0.021	0.007	-10000	0	-10000	0	0
XPO1	0.023	0.003	-10000	0	-10000	0	0
NEMO/ATM	0.01	0.11	0.26	1	-0.35	37	38
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.031	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0.013	0.097	-10000	0	-0.32	35	35
BCL10/MALT1/TRAF6	0.043	0.013	-10000	0	-10000	0	0
NOD2	0.021	0.021	0.28	1	-0.35	1	2
NFKB1	0.023	0.017	-10000	0	-0.35	1	1
RELA	0.024	0.005	-10000	0	-10000	0	0
MALT1	0.022	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.032	0.008	-10000	0	-10000	0	0
ATM	0.022	0.005	-10000	0	-10000	0	0
TNF/TNFR1A	0.052	0.06	0.21	62	-0.25	2	64
TRAF6	0.022	0.005	-10000	0	-10000	0	0
PRKCA	0	0.087	-10000	0	-0.35	31	31
CHUK	0.022	0.005	-10000	0	-10000	0	0
UBE2D3	0.022	0.004	-10000	0	-10000	0	0
TNF	0.053	0.088	0.28	66	-0.35	2	68
NF kappa B1 p50/RelA	0.047	0.018	-10000	0	-0.2	1	1
BCL10	0.023	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.008	0.028	0.2	8	-10000	0	8
beta TrCP1/SCF ubiquitin ligase complex	0.024	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
IKK complex	0.014	0.1	0.26	1	-0.34	35	36
CYLD	0.021	0.006	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.012	0.11	-10000	0	-0.35	33	33

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.014	0.02	-10000	0	-0.16	1	1
TRAF2/ASK1	0.028	0.013	-10000	0	-0.2	1	1
ATM	0.022	0.005	-10000	0	-10000	0	0
MAP2K3	-0.002	0.094	0.26	1	-0.33	28	29
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.006	0.088	0.26	4	-0.33	20	24
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.014	0.055	-10000	0	-0.35	12	12
TXN	0.005	0.001	-10000	0	-10000	0	0
CALM1	0.022	0.004	-10000	0	-10000	0	0
GADD45A	0.023	0.002	-10000	0	-10000	0	0
GADD45B	0.021	0.006	-10000	0	-10000	0	0
MAP3K1	0.022	0.005	-10000	0	-10000	0	0
MAP3K6	0.022	0.004	-10000	0	-10000	0	0
MAP3K7	0.023	0.003	-10000	0	-10000	0	0
MAP3K4	0.022	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.014	-10000	0	-0.25	1	1
TAK1/TAB family	0.001	0.024	0.14	2	-0.15	4	6
RAC1/OSM/MEKK3	0.041	0.013	-10000	0	-10000	0	0
TRAF2	0.022	0.006	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.015	0.079	-10000	0	-0.31	17	17
TRAF6	0.005	0.001	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.063	0.097	0.28	86	-0.35	1	87
CCM2	0.023	0.004	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.052	0.057	0.19	77	-0.2	1	78
MAPK11	0.019	0.024	-10000	0	-0.35	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.063	0.057	0.19	79	-0.19	2	81
OSM/MEKK3	0.032	0.01	-10000	0	-10000	0	0
TAOK1	0.009	0.012	-10000	0	-0.26	1	1
TAOK2	0.01	0.003	-10000	0	-10000	0	0
TAOK3	0.01	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.023	0.004	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.022	0.016	-10000	0	-0.35	1	1
MAP3K10	0.022	0.005	-10000	0	-10000	0	0
MAP3K3	0.022	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.013	0.03	-10000	0	-0.19	1	1
GADD45/MTK1/MTK1	0.043	0.037	-10000	0	-0.18	11	11

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.05	0.034	0.21	1	-0.19	7	8
HDAC3	0.023	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.012	0.003	-10000	0	-10000	0	0
GATA1/HDAC4	0.031	0.007	-10000	0	-10000	0	0
GATA1/HDAC5	0.03	0.009	-10000	0	-10000	0	0
GATA2/HDAC5	0.006	0.08	-10000	0	-0.24	50	50
HDAC5/BCL6/BCoR	0.04	0.02	-10000	0	-0.21	1	1
HDAC9	0.016	0.048	-10000	0	-0.35	9	9
Glucocorticoid receptor/Hsp90/HDAC6	0.007	0.089	-10000	0	-0.21	77	77
HDAC4/ANKRA2	0.032	0.015	-10000	0	-0.25	1	1
HDAC5/YWHAB	0.031	0.011	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.009	0.003	-10000	0	-10000	0	0
GATA2	-0.012	0.11	-10000	0	-0.35	50	50
HDAC4/RFXANK	0.033	0.017	0.22	3	-10000	0	3
BCOR	0.023	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.021	0.007	-10000	0	-10000	0	0
HDAC5	0.022	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.028	0.037	0.21	1	-0.24	9	10
Histones	0.005	0.058	-10000	0	-0.29	6	6
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
HDAC4	0.023	0.004	-10000	0	-10000	0	0
XPO1	0.023	0.003	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.031	0.015	-10000	0	-0.25	1	1
HDAC4/Ubc9	0.032	0.009	-10000	0	-10000	0	0
HDAC7	0.022	0.005	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.031	0.011	-10000	0	-10000	0	0
TUBA1B	0.023	0.002	-10000	0	-10000	0	0
HDAC6	0.023	0.004	-10000	0	-10000	0	0
HDAC5/RFXANK	0.032	0.015	0.21	2	-10000	0	2
CAMK4	0.023	0.037	0.28	5	-0.35	3	8
Tubulin/HDAC6	0.045	0.02	0.2	3	-0.21	1	4
SUMO1	0.023	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.022	0.005	-10000	0	-10000	0	0
GATA1	0.02	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.021	0.007	-10000	0	-10000	0	0
NR3C1	-0.031	0.13	-10000	0	-0.35	77	77
SUMO1/HDAC4	0.024	0.044	-10000	0	-0.19	12	12
SRF	0.023	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.032	0.009	-10000	0	-10000	0	0
Tubulin	0.033	0.023	0.21	3	-0.25	2	5
HDAC4/14-3-3 E	0.031	0.01	-10000	0	-10000	0	0
GNB1	0.022	0.004	-10000	0	-10000	0	0
RANGAP1	0.021	0.006	-10000	0	-10000	0	0
BCL6/BCoR	0.03	0.016	-10000	0	-0.25	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.044	0.012	-10000	0	-10000	0	0
HDAC4/SRF	0.044	0.024	0.2	4	-0.21	2	6
HDAC4/ER alpha	0.003	0.085	-10000	0	-0.24	56	56
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.005	0.058	-10000	0	-0.29	6	6
cell motility	0.044	0.02	0.2	3	-0.21	1	4
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.022	0.005	-10000	0	-10000	0	0
HDAC7/HDAC3	0.032	0.009	-10000	0	-10000	0	0
BCL6	0.02	0.017	-10000	0	-0.35	1	1
HDAC4/CaMK II delta B	0.023	0.004	-10000	0	-10000	0	0
Hsp90/HDAC6	0.032	0.009	-10000	0	-10000	0	0
ESR1	-0.017	0.11	-10000	0	-0.35	56	56
HDAC6/HDAC11	0.032	0.009	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.042	-10000	0	-0.18	10	10
NPC	0.014	0.001	-10000	0	-10000	0	0
MEF2C	-0.01	0.1	-10000	0	-0.35	47	47
RAN	0.023	0.003	-10000	0	-10000	0	0
HDAC4/MEF2C	0.041	0.07	-10000	0	-0.18	45	45
GNG2	0.017	0.049	0.28	1	-0.35	9	10
NCOR2	0.023	0.004	-10000	0	-10000	0	0
TUBB2A	0.022	0.03	0.28	3	-0.35	2	5
HDAC11	0.023	0.014	0.33	1	-10000	0	1
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
ANKRA2	0.021	0.017	-10000	0	-0.35	1	1
RFXANK	0.024	0.021	0.3	3	-10000	0	3
nuclear import	-0.025	0.01	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.16	0.18	-10000	0	-0.35	257	257
CLTC	0.011	0.065	-10000	0	-0.47	8	8
calcium ion-dependent exocytosis	0.007	0.031	-10000	0	-0.22	7	7
Dynamin 2/GTP	0.019	0.007	-10000	0	-10000	0	0
EXOC4	0.022	0.005	-10000	0	-10000	0	0
CD59	0.005	0.046	-10000	0	-0.38	7	7
CPE	-0.012	0.064	-10000	0	-0.2	53	53
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
membrane fusion	0.009	0.015	-10000	0	-10000	0	0
CTNND1	-0.009	0.029	0.18	12	-10000	0	12
DNM2	0.021	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.008	0.046	0.18	2	-0.34	5	7
TSHR	0.008	0.031	0.14	19	-0.2	3	22
INS	-0.01	0.1	-10000	0	-0.48	24	24
BIN1	0.02	0.032	-10000	0	-0.35	4	4
mol:Choline	0.009	0.015	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.009	0.003	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.023	0.003	-10000	0	-10000	0	0
mol:Ca2+	0.018	0.007	-10000	0	-10000	0	0
JUP	0.006	0.041	-10000	0	-0.39	5	5
ASAP2/amphiphysin II	0.04	0.021	-10000	0	-0.19	3	3
ARF6/GTP	0.017	0.003	-10000	0	-10000	0	0
CDH1	0.005	0.041	-10000	0	-0.39	5	5
clathrin-independent pinocytosis	0.017	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.022	0.005	-10000	0	-10000	0	0
positive regulation of endocytosis	0.017	0.003	-10000	0	-10000	0	0
EXOC2	0.022	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.01	0.038	-10000	0	-0.3	3	3
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.022	0.006	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.027	0.048	0.33	5	-0.25	1	6
positive regulation of phagocytosis	0.01	0.002	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.03	0.008	-10000	0	-10000	0	0
ACAP1	0.01	0.031	-10000	0	-0.18	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.006	0.04	-10000	0	-0.35	6	6
clathrin heavy chain/ACAP1	0.011	0.056	0.18	2	-0.38	7	9
JIP4/KLC1	0.04	0.013	-10000	0	-10000	0	0
EXOC1	0.023	0.003	-10000	0	-10000	0	0
exocyst	0.01	0.038	-10000	0	-0.3	3	3
RALA/GTP	0.017	0.003	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.029	0.008	-10000	0	-10000	0	0
receptor recycling	0.017	0.003	-10000	0	-10000	0	0
CTNNA1	-0.009	0.026	0.18	10	-10000	0	10
NME1	0.009	0.003	-10000	0	-10000	0	0
clathrin coat assembly	0.01	0.069	0.26	1	-0.47	8	9
IL2RA	0.008	0.048	-10000	0	-0.36	7	7
VAMP3	0.01	0.002	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.057	0.095	-10000	0	-0.36	10	10
EXOC6	0.022	0.005	-10000	0	-10000	0	0
PLD1	0.008	0.007	-10000	0	-10000	0	0
PLD2	0.009	0.005	-10000	0	-10000	0	0
EXOC5	0.023	0.004	-10000	0	-10000	0	0
PIP5K1C	0.007	0.038	-10000	0	-0.4	3	3
SDC1	0.019	0.044	-10000	0	-0.35	5	5
ARF6/GDP	0.019	0.005	-10000	0	-10000	0	0
EXOC7	0.022	0.006	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.029	0.05	0.26	1	-0.34	5	6
mol:Phosphatidic acid	0.009	0.015	-10000	0	-10000	0	0
endocytosis	-0.039	0.02	0.19	3	-10000	0	3
SCAMP2	0.022	0.005	-10000	0	-10000	0	0
ADRB2	-0.019	0.087	0.3	1	-0.42	10	11
EXOC3	0.022	0.006	-10000	0	-10000	0	0
ASAP2	0.022	0.005	-10000	0	-10000	0	0
Dynamin 2/GDP	0.022	0.009	-10000	0	-10000	0	0
KLC1	0.022	0.004	-10000	0	-10000	0	0
AVPR2	-0.038	0.1	0.23	6	-0.44	10	16
RALA	0.023	0.004	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.021	0.048	0.28	2	-0.35	4	6

×

Class I PI3K signaling events

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
ARF5/GTP	-0.021	0.028	-10000	0	-10000	0	0
DAPP1	0.023	0.081	0.24	16	-0.36	7	23
Src family/SYK family/BLNK-LAT/BTK-ITK	0.016	0.1	0.31	4	-0.46	12	16
mol:DAG	0.013	0.06	0.22	21	-0.18	2	23
HRAS	0.023	0.007	-10000	0	-10000	0	0
RAP1A	0.024	0.005	-10000	0	-10000	0	0
ARF5/GDP	0.011	0.072	-10000	0	-0.3	10	10
PLCG2	0.02	0.021	0.28	1	-0.35	1	2
PLCG1	0.022	0.005	-10000	0	-10000	0	0
ARF5	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	-0.017	0.026	0.14	12	-10000	0	12
ARF1/GTP	-0.008	0.027	0.23	1	-10000	0	1
RHOA	0.022	0.005	-10000	0	-10000	0	0
YES1	0.022	0.005	-10000	0	-10000	0	0
RAP1A/GTP	-0.017	0.027	0.15	12	-10000	0	12
ADAP1	-0.019	0.025	0.15	2	-10000	0	2
ARAP3	-0.017	0.025	0.14	12	-10000	0	12
INPPL1	0.023	0.003	-10000	0	-10000	0	0
PREX1	0.022	0.005	-10000	0	-10000	0	0
ARHGEF6	0.015	0.055	-10000	0	-0.35	12	12
ARHGEF7	0.022	0.005	-10000	0	-10000	0	0
ARF1	0.02	0.008	-10000	0	-10000	0	0
NRAS	0.024	0.005	-10000	0	-10000	0	0
FYN	0.023	0.004	-10000	0	-10000	0	0
ARF6	0.023	0.003	-10000	0	-10000	0	0
FGR	0.016	0.051	-10000	0	-0.35	10	10
mol:Ca2+	0.009	0.051	0.18	29	-10000	0	29
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.014	0.057	-10000	0	-0.35	13	13
ZAP70	0.029	0.05	0.28	16	-0.35	2	18
mol:IP3	0.009	0.061	0.21	29	-0.14	2	31
LYN	0.021	0.007	-10000	0	-10000	0	0
ARF1/GDP	0.008	0.07	0.2	1	-0.28	10	11
RhoA/GDP	0.018	0.046	0.24	3	-0.22	1	4
PDK1/Src/Hsp90	0.042	0.015	-10000	0	-10000	0	0
BLNK	0.021	0.026	0.28	1	-0.35	2	3
actin cytoskeleton reorganization	0.002	0.066	0.25	12	-0.28	6	18
SRC	0.022	0.005	-10000	0	-10000	0	0
PLEKHA2	-0.012	0.01	-10000	0	-0.21	1	1
RAC1	0.022	0.005	-10000	0	-10000	0	0
PTEN	0.022	0.01	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.02	0.03	-10000	0	-10000	0	0
RhoA/GTP	-0.019	0.027	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	0.02	0.06	0.21	4	-0.29	7	11
BLK	0.037	0.068	0.28	38	-10000	0	38
PDPK1	0.022	0.005	-10000	0	-10000	0	0
CYTH1	-0.018	0.027	0.15	2	-10000	0	2
HCK	0.025	0.03	0.28	7	-10000	0	7
CYTH3	-0.019	0.025	0.15	2	-10000	0	2
CYTH2	-0.019	0.026	0.14	3	-10000	0	3
KRAS	0.023	0.013	0.3	1	-10000	0	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.006	0.035	-10000	0	-0.36	2	2
SGK1	0.011	0.037	-10000	0	-0.38	2	2
INPP5D	0.022	0.016	-10000	0	-0.35	1	1
mol:GDP	-0.001	0.072	0.18	4	-0.25	21	25
SOS1	0.023	0.003	-10000	0	-10000	0	0
SYK	0.022	0.012	0.28	1	-10000	0	1
ARF6/GDP	-0.012	0.042	0.22	4	-0.22	1	5
mol:PI-3-4-5-P3	-0.017	0.026	0.15	2	-10000	0	2
ARAP3/RAP1A/GTP	-0.017	0.028	0.16	12	-10000	0	12
VAV1	0.023	0.03	0.28	5	-0.35	1	6
mol:PI-3-4-P2	-0.012	0.01	-10000	0	-0.25	1	1
RAS family/GTP/PI3K Class I	0.034	0.031	0.32	1	-0.16	1	2
PLEKHA1	-0.013	0.009	-10000	0	-0.21	1	1
Rac1/GDP	0.011	0.071	-10000	0	-0.3	10	10
LAT	0.022	0.005	-10000	0	-10000	0	0
Rac1/GTP	0	0.079	-10000	0	-0.3	26	26
ITK	-0.023	0.033	0.14	1	-0.18	11	12
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.013	0.068	0.27	13	-0.25	2	15
LCK	0.024	0.028	0.28	4	-0.35	1	5
BTK	-0.02	0.028	0.15	2	-0.18	2	4

×

TRAIL signaling 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
TNFSF10	0.02	0.037	0.33	3	-0.35	3	6
positive regulation of NF-kappaB transcription factor activity	0.022	0.046	0.24	3	-0.24	12	15
MAP2K4	0.006	0.04	0.24	1	-0.24	6	7
IKBKB	0.021	0.007	-10000	0	-10000	0	0
TNFRSF10B	0.02	0.008	-10000	0	-10000	0	0
TNFRSF10A	0.02	0.008	-10000	0	-10000	0	0
SMPD1	0.008	0.015	0.15	3	-0.15	2	5
IKBKG	0.023	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.012	0.053	-10000	0	-0.35	11	11
TRAIL/TRAILR2	0.027	0.027	0.24	3	-0.25	2	5
TRAIL/TRAILR3	0.027	0.029	0.24	3	-0.25	3	6
TRAIL/TRAILR1	0.027	0.027	0.24	3	-0.25	2	5
TRAIL/TRAILR4	0.022	0.046	0.24	3	-0.25	12	15
TRAIL/TRAILR1/DAP3/GTP	0.028	0.028	0.22	2	-0.19	2	4
IKK complex	0.012	0.032	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.014	0.007	-10000	0	-10000	0	0
MAPK3	-0.01	0.029	0.3	3	-0.24	3	6
MAP3K1	0.012	0.038	0.26	1	-0.22	4	5
TRAILR4 (trimer)	0.012	0.053	-10000	0	-0.35	11	11
TRADD	0.02	0.008	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.02	0.008	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.013	0.027	0.17	1	-0.17	9	10
CFLAR	0.023	0.003	-10000	0	-10000	0	0
MAPK1	-0.01	0.026	0.3	2	-0.24	3	5
TRAIL/TRAILR1/FADD/TRADD/RIP	0.05	0.036	0.23	2	-0.18	2	4
mol:ceramide	0.008	0.015	0.15	3	-0.15	2	5
FADD	0.022	0.004	-10000	0	-10000	0	0
MAPK8	0.009	0.051	0.19	6	-0.24	6	12
TRAF2	0.022	0.006	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.019	0.018	-10000	0	-0.35	1	1
CHUK	0.022	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.036	0.027	0.23	2	-0.21	2	4
DAP3	0.019	0.009	-10000	0	-10000	0	0
CASP10	0.009	0.059	0.17	49	-0.36	2	51
JNK cascade	0.022	0.046	0.24	3	-0.24	12	15
TRAIL (trimer)	0.02	0.037	0.33	3	-0.35	3	6
TNFRSF10C	0.019	0.018	-10000	0	-0.35	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	0.034	0.031	0.22	1	-0.18	2	3
TRAIL/TRAILR2/FADD	0.036	0.027	0.23	2	-0.21	2	4
cell death	0.008	0.015	0.15	3	-0.15	2	5
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.013	0.027	0.17	1	-0.17	9	10
TRAILR2 (trimer)	0.02	0.008	-10000	0	-10000	0	0
CASP8	0.013	0.038	-10000	0	-0.54	2	2
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.05	0.036	0.23	2	-0.18	2	4

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.057	0.071	0.23	2	-0.25	5	7
Ran/GTP/Exportin 1/HDAC1	-0.012	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.032	0.06	-10000	0	-0.28	8	8
SUMO1	0.023	0.003	-10000	0	-10000	0	0
ZFPM1	0.02	0.018	-10000	0	-0.35	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.009	0.003	-10000	0	-10000	0	0
FKBP3	0.023	0.004	-10000	0	-10000	0	0
Histones	0.055	0.038	-10000	0	-10000	0	0
YY1/LSF	0.007	0.069	-10000	0	-0.23	32	32
SMG5	0.019	0.009	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.026	0.029	0.17	7	-0.19	2	9
I kappa B alpha/HDAC1	0.032	0.034	-10000	0	-10000	0	0
SAP18	0.022	0.005	-10000	0	-10000	0	0
RELA	0.025	0.035	0.19	7	-0.17	2	9
HDAC1/Smad7	0.042	0.02	-10000	0	-0.21	2	2
RANGAP1	0.021	0.006	-10000	0	-10000	0	0
HDAC3/TR2	0.033	0.036	-10000	0	-0.16	7	7
NuRD/MBD3 Complex	0.027	0.042	-10000	0	-0.35	1	1
NF kappa B1 p50/RelA	0.022	0.07	0.23	1	-0.29	13	14
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.012	0.11	-10000	0	-0.35	50	50
GATA1	0.02	0.005	-10000	0	-10000	0	0
Mad/Max	0.033	0.008	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.017	0.072	-10000	0	-0.35	7	7
RBBP7	0.023	0.003	-10000	0	-10000	0	0
NPC	0.014	0.001	-10000	0	-10000	0	0
RBBP4	0.02	0.028	-10000	0	-0.35	3	3
MAX	0.023	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.023	0.004	-10000	0	-10000	0	0
NFKBIA	0.022	0.022	0.15	2	-10000	0	2
KAT2B	0.017	0.045	-10000	0	-0.35	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.012	0.028	-10000	0	-10000	0	0
SIN3 complex	0.052	0.021	-10000	0	-10000	0	0
SMURF1	0.023	0.004	-10000	0	-10000	0	0
CHD3	0.021	0.006	-10000	0	-10000	0	0
SAP30	0.022	0.004	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.021	0.007	-10000	0	-10000	0	0
YY1/HDAC3	0.015	0.057	-10000	0	-0.28	8	8
YY1/HDAC2	0.009	0.065	-10000	0	-0.22	28	28
YY1/HDAC1	0.012	0.061	-10000	0	-0.22	25	25
NuRD/MBD2 Complex (MeCP1)	0.027	0.044	-10000	0	-0.3	2	2
PPARG	0.011	0.07	0.19	5	-0.26	25	30
HDAC8/hEST1B	0.036	0.02	-10000	0	-10000	0	0
UBE2I	0.022	0.005	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.032	0.035	-10000	0	-10000	0	0
MBD3L2	0.016	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.042	0.02	-10000	0	-0.21	2	2
CREBBP	0.022	0.005	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.02	0.068	-10000	0	-0.29	13	13
HDAC1	0.023	0.004	-10000	0	-10000	0	0
HDAC3	0.022	0.022	0.15	6	-0.14	2	8
HDAC2	0.023	0.003	-10000	0	-10000	0	0
YY1	0.01	0.025	-10000	0	-0.22	6	6
HDAC8	0.023	0.002	-10000	0	-10000	0	0
SMAD7	0.021	0.023	-10000	0	-0.35	2	2
NCOR2	0.023	0.004	-10000	0	-10000	0	0
MXD1	0.023	0.004	-10000	0	-10000	0	0
STAT3	0.014	0.005	-10000	0	-10000	0	0
NFKB1	0.022	0.017	-10000	0	-0.35	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.022	0.065	-10000	0	-0.2	28	28
YY1/SAP30/HDAC1	0.024	0.061	-10000	0	-0.2	23	23
EP300	0.021	0.006	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.014	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.022	0.15	2	-10000	0	2
histone deacetylation	0.027	0.043	-10000	0	-0.3	2	2
STAT3 (dimer non-phopshorylated)/HDAC3	0.022	0.033	-10000	0	-0.24	2	2
nuclear export	-0.035	0.02	-10000	0	-10000	0	0
PRKACA	0.022	0.005	-10000	0	-10000	0	0
GATAD2B	0.019	0.009	-10000	0	-10000	0	0
GATAD2A	0.022	0.005	-10000	0	-10000	0	0
GATA2/HDAC3	0.013	0.069	-10000	0	-0.18	45	45
GATA1/HDAC1	0.03	0.008	-10000	0	-10000	0	0
GATA1/HDAC3	0.029	0.036	-10000	0	-0.16	2	2
CHD4	0.022	0.004	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.052	0.06	0.21	62	-0.25	2	64
SIN3/HDAC complex/Mad/Max	0.016	0.047	-10000	0	-0.32	5	5
NuRD Complex	0.023	0.063	-10000	0	-0.32	8	8
positive regulation of chromatin silencing	0.052	0.036	-10000	0	-10000	0	0
SIN3B	0.022	0.006	-10000	0	-10000	0	0
MTA2	0.023	0.003	-10000	0	-10000	0	0
SIN3A	0.022	0.005	-10000	0	-10000	0	0
XPO1	0.023	0.003	-10000	0	-10000	0	0
SUMO1/HDAC1	0.025	0.042	-10000	0	-0.19	9	9
HDAC complex	0.054	0.024	-10000	0	-0.19	3	3
GATA1/Fog1	0.027	0.017	-10000	0	-0.25	1	1
FKBP25/HDAC1/HDAC2	0.044	0.012	-10000	0	-10000	0	0
TNF	0.053	0.088	0.28	66	-0.35	2	68
negative regulation of cell growth	0.016	0.047	-10000	0	-0.32	5	5
NuRD/MBD2/PRMT5 Complex	0.027	0.044	-10000	0	-0.3	2	2
Ran/GTP/Exportin 1	0.026	0.042	-10000	0	-0.18	10	10
NF kappa B/RelA/I kappa B alpha	0.02	0.055	0.18	6	-0.28	8	14
SIN3/HDAC complex/NCoR1	0.006	0.064	-10000	0	-0.4	8	8
TFCP2	0.019	0.039	-10000	0	-0.35	6	6
NR2C1	0.023	0.002	-10000	0	-10000	0	0
MBD3	0.021	0.006	-10000	0	-10000	0	0
MBD2	0.022	0.004	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.011	0.016	0.24	2	-10000	0	2
SNTA1	0.022	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.011	0.016	0.24	2	-10000	0	2
MAPK12	-0.003	0.014	0.2	1	-0.18	1	2
CCND1	0.007	0.03	0.18	1	-0.33	3	4
p38 gamma/SNTA1	0.02	0.037	0.21	14	-0.17	1	15
MAP2K3	0.021	0.006	-10000	0	-10000	0	0
PKN1	0.022	0.006	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.003	0.014	0.2	1	-0.18	1	2
MAP2K6	0.001	0.015	0.24	1	-10000	0	1
MAPT	-0.002	0.063	0.16	20	-0.24	25	45
MAPK13	-0.009	0.021	0.17	6	-10000	0	6
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.005	0.001	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	0.021	0.017	-10000	0	-0.35	1	1
PLK4	0.025	0.027	0.28	6	-10000	0	6
regulation of centriole replication	-0.011	0.015	0.11	4	-0.25	1	5

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.022	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.012	-10000	0	-10000	0	0
DOCK1	0.017	0.042	-10000	0	-0.35	7	7
ITGA4	0.022	0.025	0.28	1	-0.35	2	3
RAC1	0.022	0.005	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.034	0.017	0.21	2	-0.25	1	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.042	0.022	0.2	1	-0.21	2	3
alpha4/beta7 Integrin/Paxillin	0.034	0.018	0.19	2	-0.19	1	3
lamellipodium assembly	-0.007	0.093	-10000	0	-0.39	23	23
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
PI3K	0.027	0.029	-10000	0	-0.25	5	5
ARF6	0.023	0.003	-10000	0	-10000	0	0
TLN1	0.022	0.005	-10000	0	-10000	0	0
PXN	-0.011	0.003	-10000	0	-10000	0	0
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
ARF6/GTP	0.041	0.023	-10000	0	-0.17	2	2
cell adhesion	0.041	0.023	0.19	1	-0.18	2	3
CRKL/CBL	0.032	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.032	0.019	0.19	1	-0.19	2	3
ITGB1	0.022	0.004	-10000	0	-10000	0	0
ITGB7	0.023	0.011	0.28	1	-10000	0	1
ARF6/GDP	0.021	0.012	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.03	0.06	0.2	1	-0.19	33	34
p130Cas/Crk/Dock1	0.036	0.033	-10000	0	-0.21	7	7
VCAM1	-0.004	0.097	-10000	0	-0.35	39	39
alpha4/beta1 Integrin/Paxillin/Talin	0.042	0.024	0.2	1	-0.18	2	3
alpha4/beta1 Integrin/Paxillin/GIT1	0.043	0.023	0.2	1	-0.18	2	3
BCAR1	0.021	0.007	-10000	0	-10000	0	0
mol:GDP	-0.041	0.023	0.18	2	-0.19	1	3
CBL	0.022	0.005	-10000	0	-10000	0	0
PRKACA	0.022	0.005	-10000	0	-10000	0	0
GIT1	0.022	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.042	0.024	0.2	1	-0.18	2	3
Rac1/GTP	-0.008	0.1	-10000	0	-0.44	23	23

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.022	0.005	-10000	0	-10000	0	0
SMAD2	0.002	0.042	0.22	6	-0.27	3	9
SMAD3	0.013	0.024	-10000	0	-0.25	1	1
SMAD3/SMAD4	0.019	0.094	-10000	0	-0.48	16	16
SMAD4/Ubc9/PIASy	0.041	0.016	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.046	0.053	0.24	3	-0.24	2	5
PPM1A	0.022	0.004	-10000	0	-10000	0	0
CALM1	0.022	0.004	-10000	0	-10000	0	0
SMAD2/SMAD4	0.014	0.041	0.22	3	-0.24	4	7
MAP3K1	0.022	0.005	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.029	0.034	-10000	0	-0.24	8	8
MAPK3	0.022	0.005	-10000	0	-10000	0	0
MAPK1	0.022	0.005	-10000	0	-10000	0	0
NUP214	0.022	0.006	-10000	0	-10000	0	0
CTDSP1	0.023	0.004	-10000	0	-10000	0	0
CTDSP2	0.023	0.001	-10000	0	-10000	0	0
CTDSPL	0.022	0.004	-10000	0	-10000	0	0
KPNB1	0.022	0.005	-10000	0	-10000	0	0
TGFBRAP1	0.017	0.045	-10000	0	-0.35	8	8
UBE2I	0.022	0.005	-10000	0	-10000	0	0
NUP153	0.022	0.017	-10000	0	-0.35	1	1
KPNA2	0.035	0.059	0.3	25	-10000	0	25
PIAS4	0.021	0.007	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.015	0.022	-10000	0	-10000	0	0
regulation of axonogenesis	-0.004	0.023	0.24	4	-10000	0	4
myoblast fusion	-0.02	0.027	-10000	0	-10000	0	0
mol:GTP	0.017	0.023	-10000	0	-0.16	8	8
regulation of calcium-dependent cell-cell adhesion	-0.037	0.042	0.19	12	-10000	0	12
ARF1/GTP	0.025	0.023	-10000	0	-10000	0	0
mol:GM1	0.007	0.016	-10000	0	-10000	0	0
mol:Choline	0.004	0.014	-10000	0	-0.19	1	1
lamellipodium assembly	0.007	0.05	-10000	0	-0.36	8	8
MAPK3	0.017	0.017	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.038	0.043	-10000	0	-0.19	12	12
ARF1	0.02	0.008	-10000	0	-10000	0	0
ARF6/GDP	0.02	0.027	-10000	0	-10000	0	0
ARF1/GDP	0.018	0.039	-10000	0	-0.21	8	8
ARF6	0.029	0.009	-10000	0	-10000	0	0
RAB11A	0.022	0.005	-10000	0	-10000	0	0
TIAM1	0.013	0.058	-10000	0	-0.35	13	13
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.019	-10000	0	-10000	0	0
actin filament bundle formation	-0.025	0.036	0.22	5	-10000	0	5
KALRN	0.008	0.022	-10000	0	-0.18	4	4
RAB11FIP3/RAB11A	0.032	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.025	0.036	-10000	0	-0.22	5	5
NME1	0.022	0.008	-10000	0	-10000	0	0
Rac1/GDP	0.025	0.038	-10000	0	-0.22	8	8
substrate adhesion-dependent cell spreading	0.016	0.023	-10000	0	-0.16	8	8
cortical actin cytoskeleton organization	0.007	0.05	-10000	0	-0.36	8	8
RAC1	0.022	0.005	-10000	0	-10000	0	0
liver development	0.016	0.023	-10000	0	-0.16	8	8
ARF6/GTP	0.017	0.023	-10000	0	-0.16	8	8
RhoA/GTP	0.029	0.021	-10000	0	-10000	0	0
mol:GDP	0.009	0.028	-10000	0	-0.22	6	6
ARF6/GTP/RAB11FIP3/RAB11A	0.041	0.02	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
PLD1	0.013	0.017	-10000	0	-10000	0	0
RAB11FIP3	0.022	0.005	-10000	0	-10000	0	0
tube morphogenesis	0.007	0.05	-10000	0	-0.36	8	8
ruffle organization	0.004	0.023	-10000	0	-0.24	4	4
regulation of epithelial cell migration	0.016	0.023	-10000	0	-0.16	8	8
PLD2	0.014	0.017	-10000	0	-0.21	1	1
PIP5K1A	0.004	0.023	-10000	0	-0.24	4	4
mol:Phosphatidic acid	0.004	0.014	-10000	0	-0.19	1	1
Rac1/GTP	0.007	0.05	-10000	0	-0.36	8	8

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.024	0.008	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.008	0.002	-10000	0	-10000	0	0
mol:DAG	-0.011	0.013	0.18	2	-10000	0	2
VEGFR1 homodimer/NRP1/VEGFR 121	0.022	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.019	0.01	-10000	0	-10000	0	0
HIF1A	0.026	0.005	-10000	0	-10000	0	0
GAB1	0.02	0.032	-10000	0	-0.35	4	4
AKT1	0.002	0.054	0.48	1	-10000	0	1
PLCG1	-0.011	0.013	0.18	2	-10000	0	2
NOS3	0.013	0.049	0.43	2	-0.35	1	3
CBL	0.022	0.005	-10000	0	-10000	0	0
mol:NO	0.02	0.065	0.38	7	-0.34	1	8
FLT1	0.011	0.003	-10000	0	-10000	0	0
PGF	0.023	0.012	0.28	1	-10000	0	1
VEGFR1 homodimer/NRP2/VEGFR121	0.026	0.047	-10000	0	-10000	0	0
CALM1	0.022	0.004	-10000	0	-10000	0	0
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
eNOS/Hsp90	0.027	0.056	0.39	1	-0.32	1	2
endothelial cell proliferation	-0.009	0.065	0.32	4	-0.28	4	8
mol:Ca2+	-0.011	0.013	0.18	2	-10000	0	2
MAPK3	-0.02	0.047	0.34	4	-10000	0	4
MAPK1	-0.02	0.047	0.34	4	-10000	0	4
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
PLGF homodimer	0.023	0.012	0.28	1	-10000	0	1
PRKACA	0.022	0.005	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.04	0.14	-10000	0	-0.35	89	89
VEGFA homodimer	0.023	0.003	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.024	0.008	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.021	0.045	0.33	4	-10000	0	4
PI3K	0.041	0.03	-10000	0	-10000	0	0
PRKCA	-0.021	0.037	0.17	1	-10000	0	1
PRKCB	-0.021	0.037	0.17	2	-10000	0	2
VEGFR1 homodimer/PLGF homodimer	0.024	0.011	-10000	0	-10000	0	0
VEGFA	0.023	0.003	-10000	0	-10000	0	0
VEGFB	0.022	0.004	-10000	0	-10000	0	0
mol:IP3	-0.011	0.013	0.18	2	-10000	0	2
RASA1	-0.012	0.024	0.18	4	-10000	0	4
NRP2	0.006	0.077	-10000	0	-0.35	24	24
VEGFR1 homodimer	0.011	0.003	-10000	0	-10000	0	0
VEGFB homodimer	0.022	0.004	-10000	0	-10000	0	0
NCK1	0.021	0.023	-10000	0	-0.35	2	2
eNOS/Caveolin-1	0.003	0.088	0.45	4	-0.3	3	7
PTPN11	0.023	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.039	0.029	-10000	0	-10000	0	0
mol:L-citrulline	0.02	0.065	0.38	7	-0.34	1	8
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.046	0.017	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.034	0.019	-10000	0	-10000	0	0
CD2AP	0.023	0.004	-10000	0	-10000	0	0
PI3K/GAB1	0.047	0.036	-10000	0	-10000	0	0
PDPK1	-0.002	0.053	0.33	1	-10000	0	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.036	0.012	-10000	0	-10000	0	0
mol:NADP	0.02	0.065	0.38	7	-0.34	1	8
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.045	0.017	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.014	0.047	-10000	0	-10000	0	0

×

Arf1 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
coatomer protein complex	0.008	0.032	0.15	24	-10000	0	24
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.027	0.056	0.14	78	-0.18	7	85
AP2	0.03	0.011	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.026	0.014	-10000	0	-10000	0	0
CLTB	0.023	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.012	0.008	-10000	0	-10000	0	0
CD4	0.023	0.012	0.28	1	-10000	0	1
CLTA	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	-0.005	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.003	0.01	-10000	0	-0.14	1	1
ARF1/GTP	0.021	0.016	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.005	0.004	-10000	0	-10000	0	0
mol:Choline	0.003	0.01	-10000	0	-0.14	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.021	0.011	-10000	0	-10000	0	0
DDEF1	0.002	0.01	-10000	0	-0.15	1	1
ARF1/GDP	0.002	0.017	-10000	0	-0.11	3	3
AP2M1	0.021	0.007	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.004	0.011	-10000	0	-10000	0	0
Rac/GTP	0.019	0.008	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.025	0.016	-10000	0	-10000	0	0
ARFIP2	0.01	0.019	-10000	0	-10000	0	0
COPA	0.019	0.009	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.01	0.027	-10000	0	-0.24	1	1
ARF1/GTP/ARHGAP10	0.013	0.008	-10000	0	-10000	0	0
GGA3	0.022	0.006	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.007	0.048	-10000	0	-0.21	22	22
AP2A1	0.022	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.007	0.021	-10000	0	-0.18	6	6
ARF1/GDP/Membrin	0.008	0.057	-10000	0	-0.24	24	24
Arfaptin 2/Rac/GDP	0.021	0.018	-10000	0	-10000	0	0
CYTH2	0.027	0.01	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.025	0.015	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.016	0.003	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.011	0.019	-10000	0	-0.17	1	1
PLD2	0.003	0.01	-10000	0	-0.14	1	1
ARF-GAP1/v-SNARE	-0.005	0.001	-10000	0	-10000	0	0
PIP5K1A	0.003	0.01	-10000	0	-0.14	1	1
ARF1/GTP/Membrin/GBF1/p115	0.011	0.022	-10000	0	-0.12	4	4
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.003	0.01	-10000	0	-0.14	1	1
KDEL Receptor/Ligand/ARF-GAP1	-0.005	0.001	-10000	0	-10000	0	0
GOSR2	0.006	0.025	-10000	0	-0.32	3	3
USO1	0.005	0.029	-10000	0	-0.32	4	4
GBF1	0.004	0.034	-10000	0	-0.34	5	5
ARF1/GTP/Arfaptin 2	0.025	0.015	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.041	0.018	0.2	1	-10000	0	1

×

a4b1 and a4b7 Integrin 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
ITGB1	0.022	0.004	-10000	0	-10000	0	0
ITGB7	0.023	0.011	0.28	1	-10000	0	1
ITGA4	0.022	0.025	0.28	1	-0.35	2	3
alpha4/beta7 Integrin	0.034	0.017	0.21	2	-0.25	1	3
alpha4/beta1 Integrin	0.032	0.02	0.21	1	-0.25	2	3

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.023	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.014	0.01	-10000	0	-10000	0	0
MDM2/SUMO1	0.024	0.045	-10000	0	-0.19	12	12
HDAC4	0.023	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.013	0.009	-10000	0	-10000	0	0
SUMO1	0.023	0.003	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.007	0.014	-10000	0	-0.26	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0	0.021	-10000	0	-0.16	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
SUMO1/HDAC4	0.024	0.044	-10000	0	-0.19	12	12
SUMO1/HDAC1	0.025	0.042	-10000	0	-0.19	9	9
RANGAP1	0.021	0.006	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.054	0.018	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.009	0.003	-10000	0	-10000	0	0
Ran/GTP	0.014	0.039	-10000	0	-0.17	12	12
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.023	0.002	-10000	0	-10000	0	0
UBE2I	0.022	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.013	0.041	0.18	5	-0.18	10	15
NPC	0.014	0.001	-10000	0	-10000	0	0
PIAS2	0.022	0.005	-10000	0	-10000	0	0
PIAS1	0.022	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.032	0.012	0.21	1	-10000	0	1
FBXW11	0.023	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.02	0.013	-10000	0	-0.21	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.023	0.035	0.19	5	-0.24	1	6
NFKBIA	0.012	0.022	-10000	0	-10000	0	0
MAPK14	0.023	0.004	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.02	0.013	-10000	0	-0.21	1	1
ARRB2	0.01	0.003	-10000	0	-10000	0	0
REL	0.023	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.019	0.015	0.2	1	-0.21	1	2
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.019	0.013	-10000	0	-0.21	1	1
PIK3CA	0.02	0.018	-10000	0	-0.35	1	1
NF kappa B1 p50 dimer	0.014	0.016	0.24	1	-0.25	1	2
PIK3R1	0.018	0.036	-10000	0	-0.35	5	5
NFKB1	-0.011	0.011	-10000	0	-0.25	1	1
RELA	0.022	0.004	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.017	0.032	-10000	0	-0.25	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.022	0.035	-10000	0	-0.19	1	1
SRC	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.027	0.029	-10000	0	-0.25	5	5
NF kappa B1 p50/RelA	0.017	0.032	-10000	0	-0.25	2	2
IKBKB	0.021	0.007	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.004	-10000	0	-10000	0	0
SYK	0.022	0.012	0.28	1	-10000	0	1
I kappa B alpha/PIK3R1	0.022	0.044	0.2	6	-0.2	5	11
cell death	0.021	0.034	-10000	0	-0.19	1	1
NF kappa B1 p105/c-Rel	0.02	0.013	-10000	0	-0.21	1	1
LCK	0.024	0.028	0.28	4	-0.35	1	5
BCL3	0.023	0.012	0.28	1	-10000	0	1

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.038	0.027	-9999	-0.3	2	2
E-cadherin/beta catenin	0.029	0.021	-9999	-0.25	2	2
CTNNB1	0.022	0.004	-9999	-10000	0	0
JUP	0.021	0.017	-9999	-0.35	1	1
CDH1	0.019	0.024	-9999	-0.35	2	2

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.039	0.019	-10000	0	-10000	0	0
CLOCK	0.024	0.003	-10000	0	-10000	0	0
TIMELESS/CRY2	0.029	0.019	-10000	0	-10000	0	0
DEC1/BMAL1	0.028	0.015	-10000	0	-0.25	1	1
ATR	0.022	0.004	-10000	0	-10000	0	0
NR1D1	0.013	0.01	-10000	0	-10000	0	0
ARNTL	0.023	0.017	-10000	0	-0.35	1	1
TIMELESS	0.014	0.016	-10000	0	-10000	0	0
NPAS2	0.021	0.036	-10000	0	-0.35	5	5
CRY2	0.022	0.004	-10000	0	-10000	0	0
mol:CO	-0.006	0.004	-10000	0	-0.073	1	1
CHEK1	0.022	0.005	-10000	0	-10000	0	0
mol:HEME	0.006	0.004	0.073	1	-10000	0	1
PER1	0.02	0.017	-10000	0	-0.35	1	1
BMAL/CLOCK/NPAS2	0.048	0.028	-10000	0	-0.2	5	5
BMAL1/CLOCK	0.013	0.05	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.039	0.019	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.039	0.02	-10000	0	-10000	0	0
mol:NADPH	0.006	0.004	0.073	1	-10000	0	1
PER1/TIMELESS	0.026	0.02	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.016	0.005	-10000	0	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.031	0.01	-9999	-10000	0	0
FBXW11	0.023	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.004	-9999	-10000	0	0
CHUK	0.022	0.005	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.059	0.025	-9999	-10000	0	0
NFKB1	0.022	0.017	-9999	-0.35	1	1
MAP3K14	0.022	0.005	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.031	0.015	-9999	-0.25	1	1
RELB	0.022	0.005	-9999	-10000	0	0
NFKB2	0.022	0.005	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.029	0.009	-9999	-10000	0	0
regulation of B cell activation	0.028	0.009	-9999	-10000	0	0

pid_entity	TCGA.SL.A6JA	TCGA.SL.A6J9	TCGA.SJ.A6ZJ	TCGA.SJ.A6ZI
109_MAP3K5	-0.14	0.019	0.019	0.019
47_PPARGC1A	-0.35	0.023	0.023	-0.35
105_BMP4	0.023	-0.35	0.023	0.023
105_BMP6	0.023	0.023	0.023	0.023
105_BMP7	0.023	0	0.023	0.023
105_BMP2	0.023	-0.35	0.023	0.023
131_RELN/VLDLR	-0.19	0	0.06	-0.19
30_TGFB1/TGF beta receptor Type II	0.023	0.023	0.02	0.023
84_STAT5B	-0.031	0.028	-0.031	0.024
84_STAT5A	-0.031	0.028	-0.031	0.024