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

Pathway.Name	Avg.Num.Perturbations
Aurora B signaling	169
FOXM1 transcription factor network	168
Aurora C signaling	137
HIF-1-alpha transcription factor network	124
Signaling events regulated by Ret tyrosine kinase	111
Endothelins	111
Angiopoietin receptor Tie2-mediated signaling	107
PDGFR-alpha signaling pathway	99
p75(NTR)-mediated signaling	95
Signaling events mediated by the Hedgehog family	84

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	0.3101	169	11375	67	-0.52	0.011	1000	-1000	-0.034	-1000
FOXM1 transcription factor network	0.3083	168	8577	51	-0.97	0.011	1000	-1000	-0.15	-1000
Aurora C signaling	0.2514	137	961	7	-0.29	0.009	1000	-1000	-0.017	-1000
HIF-1-alpha transcription factor network	0.2275	124	9442	76	-0.49	0.017	1000	-1000	-0.07	-1000
Signaling events regulated by Ret tyrosine kinase	0.2037	111	9153	82	-0.19	0.011	1000	-1000	-0.05	-1000
Endothelins	0.2037	111	10672	96	-0.34	0.011	1000	-1000	-0.043	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1963	107	9457	88	-0.32	0.043	1000	-1000	-0.075	-1000
PDGFR-alpha signaling pathway	0.1817	99	4373	44	-0.29	0.025	1000	-1000	-0.034	-1000
p75(NTR)-mediated signaling	0.1743	95	11995	125	-0.2	0.03	1000	-1000	-0.054	-1000
Signaling events mediated by the Hedgehog family	0.1541	84	4381	52	-0.26	0.14	1000	-1000	-0.023	-1000
Integrins in angiogenesis	0.1450	79	6710	84	-0.29	0.024	1000	-1000	-0.051	-1000
Cellular roles of Anthrax toxin	0.1303	71	2774	39	-0.13	0.019	1000	-1000	-0.013	-1000
Nongenotropic Androgen signaling	0.1248	68	3581	52	-0.22	0.11	1000	-1000	-0.032	-1000
S1P3 pathway	0.1229	67	2834	42	-0.41	0.016	1000	-1000	-0.022	-1000
Fc-epsilon receptor I signaling in mast cells	0.1174	64	6231	97	-0.13	0.028	1000	-1000	-0.043	-1000
PLK1 signaling events	0.1028	56	4799	85	-0.3	0.044	1000	-1000	-0.026	-1000
Effects of Botulinum toxin	0.1028	56	1473	26	-0.11	0.018	1000	-1000	-0.034	-1000
LPA4-mediated signaling events	0.1009	55	668	12	-0.12	0.015	1000	-1000	-0.007	-1000
Glypican 1 network	0.1009	55	2653	48	-0.22	0.022	1000	-1000	-0.018	-1000
Signaling mediated by p38-alpha and p38-beta	0.1009	55	2461	44	-0.084	0.011	1000	-1000	-0.036	-1000
Reelin signaling pathway	0.0991	54	3055	56	-0.15	0.03	1000	-1000	-0.044	-1000
Aurora A signaling	0.0917	50	3032	60	-0.25	0.022	1000	-1000	-0.015	-1000
IGF1 pathway	0.0917	50	2871	57	-0.075	0.022	1000	-1000	-0.051	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0862	47	5674	120	-0.19	0.14	1000	-1000	-0.041	-1000
TCGA08_retinoblastoma	0.0844	46	368	8	-0.13	0.024	1000	-1000	-0.008	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0844	46	3660	78	-0.1	0.043	1000	-1000	-0.04	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0826	45	3107	68	-0.2	0.079	1000	-1000	-0.085	-1000
Thromboxane A2 receptor signaling	0.0807	44	4664	105	-0.18	0.031	1000	-1000	-0.04	-1000
Wnt signaling	0.0807	44	311	7	-0.088	-0.003	1000	-1000	-0.016	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0771	42	1442	34	-0.039	0.011	1000	-1000	-0.015	-1000
Syndecan-1-mediated signaling events	0.0752	41	1402	34	-0.17	0.011	1000	-1000	-0.023	-1000
Plasma membrane estrogen receptor signaling	0.0752	41	3587	86	-0.15	0.066	1000	-1000	-0.048	-1000
FOXA2 and FOXA3 transcription factor networks	0.0734	40	1841	46	-0.22	0.016	1000	-1000	-0.061	-1000
BMP receptor signaling	0.0734	40	3258	81	-0.28	0.038	1000	-1000	-0.059	-1000
Ephrin B reverse signaling	0.0734	40	1948	48	-0.098	0.016	1000	-1000	-0.037	-1000
amb2 Integrin signaling	0.0716	39	3207	82	-0.15	0.022	1000	-1000	-0.05	-1000
Ephrin A reverse signaling	0.0697	38	271	7	-0.023	0	1000	-1000	-0.009	-1000
Noncanonical Wnt signaling pathway	0.0697	38	1012	26	-0.14	0.011	1000	-1000	-0.023	-1000
Ras signaling in the CD4+ TCR pathway	0.0679	37	642	17	-0.077	0.015	1000	-1000	-0.021	-1000
Osteopontin-mediated events	0.0642	35	1348	38	-0.12	0.014	1000	-1000	-0.052	-1000
IL4-mediated signaling events	0.0642	35	3229	91	-0.52	0.26	1000	-1000	-0.12	-1000
TCGA08_p53	0.0606	33	231	7	-0.089	0.047	1000	-1000	-0.006	-1000
LPA receptor mediated events	0.0606	33	3404	102	-0.14	0.029	1000	-1000	-0.05	-1000
S1P5 pathway	0.0569	31	528	17	-0.1	0.033	1000	-1000	-0.015	-1000
S1P1 pathway	0.0550	30	1102	36	-0.13	0.011	1000	-1000	-0.036	-1000
FAS signaling pathway (CD95)	0.0550	30	1419	47	-0.076	0.038	1000	-1000	-0.024	-1000
Glypican 2 network	0.0550	30	123	4	-0.014	-0.001	1000	-1000	-0.01	-1000
Arf6 signaling events	0.0532	29	1800	62	-0.086	0.027	1000	-1000	-0.027	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0532	29	1546	52	-0.078	0.022	1000	-1000	-0.032	-1000
EGFR-dependent Endothelin signaling events	0.0532	29	610	21	-0.12	0.019	1000	-1000	-0.042	-1000
Coregulation of Androgen receptor activity	0.0477	26	2008	76	-0.13	0.022	1000	-1000	-0.019	-1000
Visual signal transduction: Cones	0.0477	26	1003	38	-0.08	0.011	1000	-1000	-0.03	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0477	26	2210	85	-0.21	0.012	1000	-1000	-0.044	-1000
BCR signaling pathway	0.0477	26	2628	99	-0.059	0.047	1000	-1000	-0.047	-1000
Syndecan-4-mediated signaling events	0.0477	26	1770	67	-0.26	0.016	1000	-1000	-0.052	-1000
Visual signal transduction: Rods	0.0477	26	1390	52	-0.11	0.011	1000	-1000	-0.047	-1000
Calcium signaling in the CD4+ TCR pathway	0.0459	25	785	31	-0.12	0.015	1000	-1000	-0.046	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0440	24	3081	125	-0.068	0.029	1000	-1000	-0.056	-1000
Hedgehog signaling events mediated by Gli proteins	0.0422	23	1495	65	-0.1	0.039	1000	-1000	-0.036	-1000
TCGA08_rtk_signaling	0.0422	23	600	26	-0.15	0.023	1000	-1000	-0.013	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0404	22	1229	54	-0.14	0.022	1000	-1000	-0.054	-1000
Syndecan-2-mediated signaling events	0.0404	22	1572	69	-0.1	0.028	1000	-1000	-0.017	-1000
Glucocorticoid receptor regulatory network	0.0404	22	2523	114	-0.24	0.046	1000	-1000	-0.042	-1000
IL6-mediated signaling events	0.0404	22	1703	75	-0.12	0.061	1000	-1000	-0.038	-1000
IL2 signaling events mediated by STAT5	0.0404	22	498	22	-0.1	0.056	1000	-1000	-0.024	-1000
S1P4 pathway	0.0404	22	571	25	-0.1	0.024	1000	-1000	-0.016	-1000
Regulation of Androgen receptor activity	0.0404	22	1567	70	-0.22	0.023	1000	-1000	-0.048	-1000
Presenilin action in Notch and Wnt signaling	0.0385	21	1286	61	-0.12	0.031	1000	-1000	-0.044	-1000
Insulin Pathway	0.0385	21	1587	74	-0.13	0.03	1000	-1000	-0.051	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0367	20	671	33	-0.16	0.034	1000	-1000	-0.02	-1000
Signaling events mediated by PTP1B	0.0349	19	1504	76	-0.11	0.023	1000	-1000	-0.043	-1000
Regulation of nuclear SMAD2/3 signaling	0.0330	18	2465	136	-0.16	0.054	1000	-1000	-0.033	-1000
Nectin adhesion pathway	0.0330	18	1169	63	-0.068	0.021	1000	-1000	-0.043	-1000
Retinoic acid receptors-mediated signaling	0.0330	18	1097	58	-0.053	0.022	1000	-1000	-0.04	-1000
EPHB forward signaling	0.0330	18	1577	85	-0.034	0.029	1000	-1000	-0.05	-1000
Rapid glucocorticoid signaling	0.0330	18	378	20	-0.051	0.011	1000	-1000	-0.008	-1000
Class I PI3K signaling events mediated by Akt	0.0312	17	1156	68	-0.24	0.04	1000	-1000	-0.026	-1000
Canonical Wnt signaling pathway	0.0312	17	891	51	-0.097	0.05	1000	-1000	-0.031	-1000
Regulation of p38-alpha and p38-beta	0.0312	17	948	54	-0.18	0.043	1000	-1000	-0.041	-1000
BARD1 signaling events	0.0294	16	958	57	-0.13	0.028	1000	-1000	-0.037	-1000
IL1-mediated signaling events	0.0294	16	1029	62	-0.038	0.04	1000	-1000	-0.045	-1000
Regulation of Telomerase	0.0294	16	1651	102	-0.3	0.038	1000	-1000	-0.062	-1000
IL12-mediated signaling events	0.0257	14	1237	87	-0.3	0.044	1000	-1000	-0.086	-1000
FoxO family signaling	0.0257	14	901	64	-0.24	0.042	1000	-1000	-0.041	-1000
Signaling mediated by p38-gamma and p38-delta	0.0257	14	213	15	-0.017	0.021	1000	-1000	-0.017	-1000
TCR signaling in naïve CD8+ T cells	0.0257	14	1328	93	-0.045	0.041	1000	-1000	-0.048	-1000
Signaling events mediated by PRL	0.0257	14	482	34	-0.13	0.018	1000	-1000	-0.02	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0239	13	380	28	-0.1	0.032	1000	-1000	-0.016	-1000
IFN-gamma pathway	0.0239	13	950	68	-0.22	0.048	1000	-1000	-0.051	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0239	13	1119	83	-0.24	0.044	1000	-1000	-0.043	-1000
PDGFR-beta signaling pathway	0.0239	13	1286	97	-0.02	0.039	1000	-1000	-0.041	-1000
ErbB4 signaling events	0.0220	12	880	69	-0.075	0.03	1000	-1000	-0.054	-1000
Insulin-mediated glucose transport	0.0220	12	413	32	-0.24	0.025	1000	-1000	-0.029	-1000
mTOR signaling pathway	0.0220	12	636	53	-0.026	0.018	1000	-1000	-0.035	-1000
Signaling events mediated by HDAC Class III	0.0220	12	516	40	-0.079	0.016	1000	-1000	-0.025	-1000
Syndecan-3-mediated signaling events	0.0220	12	431	35	-0.09	0.03	1000	-1000	-0.019	-1000
ErbB2/ErbB3 signaling events	0.0202	11	778	65	-0.12	0.022	1000	-1000	-0.038	-1000
HIF-2-alpha transcription factor network	0.0202	11	487	43	-0.14	0.022	1000	-1000	-0.042	-1000
IL2 signaling events mediated by PI3K	0.0202	11	666	58	-0.11	0.043	1000	-1000	-0.055	-1000
Class IB PI3K non-lipid kinase events	0.0202	11	33	3	-0.003	0.003	1000	-1000	-0.009	-1000
JNK signaling in the CD4+ TCR pathway	0.0165	9	165	17	-0.014	0.034	1000	-1000	-0.022	-1000
EPO signaling pathway	0.0165	9	533	55	-0.024	0.035	1000	-1000	-0.05	-1000
Ceramide signaling pathway	0.0165	9	725	76	-0.067	0.037	1000	-1000	-0.018	-1000
Caspase cascade in apoptosis	0.0147	8	629	74	-0.032	0.035	1000	-1000	-0.024	-1000
IL27-mediated signaling events	0.0147	8	418	51	-0.056	0.014	1000	-1000	-0.05	-1000
Signaling events mediated by HDAC Class II	0.0128	7	539	75	-0.05	0.029	1000	-1000	-0.026	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0128	7	287	37	-0.02	0.027	1000	-1000	-0.028	-1000
IL23-mediated signaling events	0.0128	7	458	60	-0.046	0.043	1000	-1000	-0.12	-1000
p38 MAPK signaling pathway	0.0128	7	324	44	-0.045	0.028	1000	-1000	-0.039	-1000
ceramide signaling pathway	0.0110	6	342	49	-0.031	0.038	1000	-1000	-0.019	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0110	6	273	45	-0.032	0.057	1000	-1000	-0.049	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0092	5	417	74	-0.076	0.062	1000	-1000	-0.05	-1000
Arf6 trafficking events	0.0092	5	356	71	-0.2	0.035	1000	-1000	-0.044	-1000
Canonical NF-kappaB pathway	0.0073	4	178	39	-0.032	0.058	1000	-1000	-0.046	-1000
PLK2 and PLK4 events	0.0073	4	14	3	0.007	0.015	1000	-1000	-0.006	-1000
TRAIL signaling pathway	0.0073	4	195	48	-0.001	0.037	1000	-1000	-0.037	-1000
Class I PI3K signaling events	0.0073	4	326	73	-0.015	0.053	1000	-1000	-0.035	-1000
Signaling events mediated by HDAC Class I	0.0055	3	404	104	-0.032	0.044	1000	-1000	-0.038	-1000
VEGFR1 specific signals	0.0055	3	168	56	-0.062	0.052	1000	-1000	-0.018	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0037	2	47	23	-0.005	0.036	1000	-1000	-0.027	-1000
a4b1 and a4b7 Integrin signaling	0.0037	2	11	5	0.009	0.015	1000	-1000	-0.009	-1000
Paxillin-dependent events mediated by a4b1	0.0037	2	105	36	-0.031	0.032	1000	-1000	-0.037	-1000
E-cadherin signaling in keratinocytes	0.0037	2	94	43	-0.034	0.037	1000	-1000	-0.035	-1000
Arf6 downstream pathway	0.0018	1	49	43	-0.023	0.023	1000	-1000	-0.026	-1000
Atypical NF-kappaB pathway	0.0018	1	31	31	0	0.04	1000	-1000	-0.019	-1000
E-cadherin signaling in the nascent adherens junction	0.0018	1	97	76	-0.003	0.048	1000	-1000	-0.046	-1000
E-cadherin signaling events	0.0018	1	7	5	0.009	0.021	1000	-1000	-0.01	-1000
Circadian rhythm pathway	0.0000	0	16	22	-0.011	0.04	1000	-1000	-0.025	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.028	1000	-1000	-0.03	-1000
Arf1 pathway	0.0000	0	8	54	0	0.028	1000	-1000	-0.018	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	0	0.033	1000	-1000	-0.01	-1000
Total	NA	4025	240216	7203	-17	4.3	131000	-131000	-4.8	-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.12	0.064	-9999	-10000	0	0
STMN1	-0.18	0.076	-9999	-0.21	479	479
Aurora B/RasGAP/Survivin	-0.27	0.12	-9999	-0.3	493	493
Chromosomal passenger complex/Cul3 protein complex	-0.12	0.092	-9999	-0.27	106	106
BIRC5	-0.26	0.14	-9999	-0.33	423	423
DES	-0.52	0.25	-9999	-0.63	453	453
Aurora C/Aurora B/INCENP	-0.13	0.061	-9999	-0.15	322	322
Aurora B/TACC1	-0.19	0.11	-9999	-0.21	488	488
Aurora B/PP2A	-0.18	0.076	-9999	-0.21	479	479
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.024	0.014	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.004	0.003	-9999	-10000	0	0
NDC80	-0.2	0.096	-9999	-0.23	480	480
Cul3 protein complex	-0.027	0.1	-9999	-0.23	106	106
KIF2C	-0.067	0.034	-9999	-0.1	25	25
PEBP1	0.002	0.004	-9999	-10000	0	0
KIF20A	-0.3	0.1	-9999	-0.33	491	491
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.18	0.081	-9999	-0.21	479	479
SEPT1	0.01	0.018	-9999	-0.41	1	1
SMC2	0.01	0.015	-9999	-0.33	1	1
SMC4	0.011	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.009	0.015	-9999	-10000	0	0
PSMA3	0.011	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.004	0.001	-9999	-10000	0	0
H3F3B	-0.073	0.034	-9999	-10000	0	0
AURKB	-0.28	0.11	-9999	-0.33	479	479
AURKC	0.009	0.025	-9999	-0.33	3	3
CDCA8	-0.19	0.17	-9999	-0.33	318	318
cytokinesis	-0.15	0.068	-9999	-0.24	22	22
Aurora B/Septin1	-0.13	0.078	-9999	-0.23	23	23
AURKA	-0.092	0.16	-9999	-0.33	162	162
INCENP	0.004	0.004	-9999	-10000	0	0
KLHL13	-0.071	0.17	-9999	-0.41	106	106
BUB1	-0.26	0.14	-9999	-0.33	427	427
hSgo1/Aurora B/Survivin	-0.37	0.15	-9999	-0.42	478	478
EVI5	0.011	0.001	-9999	-10000	0	0
RhoA/GTP	-0.11	0.064	-9999	-0.28	23	23
SGOL1	-0.25	0.14	-9999	-0.33	423	423
CENPA	-0.1	0.05	-9999	-0.15	161	161
NCAPG	-0.22	0.16	-9999	-0.33	364	364
Aurora B/HC8 Proteasome	-0.18	0.076	-9999	-0.21	479	479
NCAPD2	0.011	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.18	0.076	-9999	-0.21	479	479
RHOA	0.011	0	-9999	-10000	0	0
NCAPH	-0.25	0.14	-9999	-0.33	421	421
NPM1	-0.041	0.018	-9999	-10000	0	0
RASA1	0.007	0.04	-9999	-0.41	5	5
KLHL9	0.01	0.018	-9999	-0.41	1	1
mitotic prometaphase	-0.009	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.076	-9999	-0.21	479	479
PPP1CC	0.011	0	-9999	-10000	0	0
Centraspindlin	-0.12	0.072	-9999	-0.25	45	45
RhoA/GDP	0.008	0	-9999	-10000	0	0
NSUN2	-0.041	0.018	-9999	-10000	0	0
MYLK	-0.24	0.15	-9999	-0.37	311	311
KIF23	-0.006	0.069	-9999	-0.33	23	23
VIM	-0.18	0.083	-9999	-0.21	479	479
RACGAP1	0.007	0.021	-9999	-0.33	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.041	0.018	-9999	-10000	0	0
Chromosomal passenger complex	-0.14	0.066	-9999	-0.18	314	314
Chromosomal passenger complex/EVI5	-0.26	0.19	-9999	-0.36	424	424
TACC1	-0.065	0.16	-9999	-0.41	98	98
PPP2R5D	0.011	0	-9999	-10000	0	0
CUL3	0.011	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

Figure S2. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S2. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.63	0.36	-9999	-0.99	203	203
PLK1	-0.15	0.088	-9999	-10000	0	0
BIRC5	-0.16	0.082	-9999	-10000	0	0
HSPA1B	-0.63	0.36	-9999	-0.99	205	205
MAP2K1	-0.021	0.017	-9999	-10000	0	0
BRCA2	-0.63	0.36	-9999	-0.99	209	209
FOXM1	-0.76	0.48	-9999	-1.1	277	277
XRCC1	-0.63	0.36	-9999	-0.97	219	219
FOXM1B/p19	-0.67	0.4	-9999	-1	262	262
Cyclin D1/CDK4	-0.58	0.33	-9999	-0.9	212	212
CDC2	-0.66	0.38	-9999	-0.98	263	263
TGFA	-0.56	0.31	-9999	-0.87	218	218
SKP2	-0.63	0.36	-9999	-0.98	216	216
CCNE1	-0.14	0.17	-9999	-0.34	220	220
CKS1B	-0.63	0.36	-9999	-0.98	216	216
RB1	-0.24	0.12	-9999	-0.96	3	3
FOXM1C/SP1	-0.69	0.42	-9999	-1	257	257
AURKB	-0.17	0.067	-9999	-10000	0	0
CENPF	-0.66	0.38	-9999	-0.97	271	271
CDK4	-0.001	0.006	-9999	-10000	0	0
MYC	-0.56	0.32	-9999	-0.87	211	211
CHEK2	-0.022	0.022	-9999	-0.35	1	1
ONECUT1	-0.61	0.35	-9999	-0.93	237	237
CDKN2A	-0.13	0.17	-9999	-0.32	228	228
LAMA4	-0.66	0.4	-9999	-1.1	215	215
FOXM1B/HNF6	-0.69	0.42	-9999	-1.1	239	239
FOS	-0.77	0.48	-9999	-1.2	259	259
SP1	0.011	0.001	-9999	-10000	0	0
CDC25B	-0.63	0.36	-9999	-0.99	205	205
response to radiation	-0.03	0.014	-9999	-10000	0	0
CENPB	-0.63	0.36	-9999	-0.99	203	203
CENPA	-0.68	0.38	-9999	-0.98	278	278
NEK2	-0.68	0.37	-9999	-1	238	238
HIST1H2BA	-0.63	0.36	-9999	-1	203	203
CCNA2	-0.071	0.14	-9999	-0.34	117	117
EP300	0.011	0	-9999	-10000	0	0
CCNB1/CDK1	-0.72	0.43	-9999	-1.1	219	219
CCNB2	-0.68	0.38	-9999	-1	243	243
CCNB1	-0.67	0.39	-9999	-1	218	218
ETV5	-0.63	0.36	-9999	-0.99	205	205
ESR1	-0.67	0.41	-9999	-1.1	218	218
CCND1	-0.59	0.33	-9999	-0.92	212	212
GSK3A	-0.014	0.014	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.12	0.14	-9999	-0.25	263	263
CDK2	0.003	0.004	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.037	0.017	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.67	0.38	-9999	-0.97	289	289
GAS1	-0.97	0.48	-9999	-1.3	377	377
MMP2	-0.64	0.38	-9999	-1	203	203
RB1/FOXM1C	-0.62	0.36	-9999	-0.95	243	243
CREBBP	0.009	0.025	-9999	-0.41	2	2

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.011	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.13	0.059	-9999	-0.16	479	479
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.038	0.014	-9999	-10000	0	0
AURKB	-0.29	0.11	-9999	-0.33	479	479
AURKC	0.009	0.025	-9999	-0.33	3	3

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.36	0.41	-9999	-0.84	169	169
HDAC7	0.012	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.3	0.36	-9999	-0.76	145	145
SMAD4	0.011	0.018	-9999	-0.41	1	1
ID2	-0.36	0.41	-9999	-0.83	174	174
AP1	-0.077	0.14	-9999	-0.29	168	168
ABCG2	-0.47	0.47	-9999	-0.92	229	229
HIF1A	-0.047	0.062	-9999	-10000	0	0
TFF3	-0.42	0.44	-9999	-0.88	209	209
GATA2	-0.029	0.12	-9999	-0.41	53	53
AKT1	-0.061	0.084	-9999	-0.22	14	14
response to hypoxia	-0.078	0.087	-9999	-0.21	77	77
MCL1	-0.36	0.41	-9999	-0.83	177	177
NDRG1	-0.36	0.41	-9999	-0.83	175	175
SERPINE1	-0.36	0.41	-9999	-0.84	174	174
FECH	-0.36	0.41	-9999	-0.84	170	170
FURIN	-0.36	0.41	-9999	-0.83	174	174
NCOA2	-0.003	0.077	-9999	-0.41	19	19
EP300	-0.073	0.13	-9999	-0.34	75	75
HMOX1	-0.36	0.41	-9999	-0.83	175	175
BHLHE40	-0.36	0.41	-9999	-0.83	174	174
BHLHE41	-0.38	0.43	-9999	-0.87	181	181
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.04	0.083	-9999	-0.3	5	5
ENG	-0.025	0.085	-9999	-0.32	1	1
JUN	0.006	0.048	-9999	-0.41	7	7
RORA	-0.37	0.42	-9999	-0.85	180	180
ABCB1	-0.35	0.49	-9999	-1.2	139	139
TFRC	-0.36	0.41	-9999	-0.83	174	174
CXCR4	-0.36	0.41	-9999	-0.84	169	169
TF	-0.37	0.42	-9999	-0.85	175	175
CITED2	-0.37	0.41	-9999	-0.84	175	175
HIF1A/ARNT	-0.39	0.48	-9999	-0.92	183	183
LDHA	-0.053	0.048	-9999	-10000	0	0
ETS1	-0.36	0.41	-9999	-0.83	174	174
PGK1	-0.36	0.41	-9999	-0.83	177	177
NOS2	-0.37	0.41	-9999	-0.85	170	170
ITGB2	-0.36	0.41	-9999	-0.83	175	175
ALDOA	-0.36	0.41	-9999	-0.83	174	174
Cbp/p300/CITED2	-0.39	0.46	-9999	-0.95	159	159
FOS	-0.12	0.19	-9999	-0.41	167	167
HK2	-0.37	0.41	-9999	-0.84	178	178
SP1	0.01	0.022	-9999	-10000	0	0
GCK	-0.23	0.46	-9999	-1.3	76	76
HK1	-0.36	0.41	-9999	-0.83	174	174
NPM1	-0.36	0.41	-9999	-0.83	174	174
EGLN1	-0.36	0.41	-9999	-0.84	169	169
CREB1	0.017	0	-9999	-10000	0	0
PGM1	-0.36	0.41	-9999	-0.83	174	174
SMAD3	0.009	0.036	-9999	-0.41	4	4
EDN1	-0.14	0.24	-9999	-0.66	55	55
IGFBP1	-0.39	0.43	-9999	-0.87	183	183
VEGFA	-0.25	0.32	-9999	-0.7	109	109
HIF1A/JAB1	-0.022	0.037	-9999	-10000	0	0
CP	-0.4	0.43	-9999	-0.88	188	188
CXCL12	-0.49	0.47	-9999	-0.93	231	231
COPS5	0.011	0.003	-9999	-10000	0	0
SMAD3/SMAD4	0.016	0.028	-9999	-0.28	5	5
BNIP3	-0.36	0.41	-9999	-0.84	169	169
EGLN3	-0.36	0.41	-9999	-0.83	175	175
CA9	-0.43	0.44	-9999	-0.87	222	222
TERT	-0.41	0.43	-9999	-0.88	195	195
ENO1	-0.36	0.41	-9999	-0.84	169	169
PFKL	-0.36	0.41	-9999	-0.84	169	169
NCOA1	0.01	0.018	-9999	-0.41	1	1
ADM	-0.37	0.41	-9999	-0.84	180	180
ARNT	-0.047	0.062	-9999	-10000	0	0
HNF4A	-0.048	0.12	-9999	-0.34	78	78
ADFP	-0.37	0.4	-9999	-0.82	186	186
SLC2A1	-0.25	0.32	-9999	-0.7	111	111
LEP	-0.36	0.41	-9999	-0.83	175	175
HIF1A/ARNT/Cbp/p300	-0.32	0.37	-9999	-0.77	154	154
EPO	-0.22	0.29	-9999	-0.84	39	39
CREBBP	-0.074	0.14	-9999	-0.34	76	76
HIF1A/ARNT/Cbp/p300/HDAC7	-0.29	0.36	-9999	-0.77	135	135
PFKFB3	-0.36	0.41	-9999	-0.84	169	169
NT5E	-0.39	0.43	-9999	-0.89	182	182

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.032	0.034	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.13	0.13	-9999	-0.33	101	101
JUN	-0.077	0.13	-9999	-0.39	36	36
HRAS	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.13	-9999	-0.23	263	263
RAP1A	0.011	0	-9999	-10000	0	0
FRS2	0.011	0	-9999	-10000	0	0
RAP1A/GDP	0.008	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.1	0.13	-9999	-0.23	262	262
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.09	0.11	-9999	-0.21	257	257
RHOA	0.011	0	-9999	-10000	0	0
RAP1A/GTP	-0.098	0.11	-9999	-0.21	173	173
GRB7	-0.011	0.084	-9999	-0.33	34	34
RET51/GFRalpha1/GDNF	-0.1	0.13	-9999	-0.23	262	262
MAPKKK cascade	-0.098	0.11	-9999	-0.37	32	32
BCAR1	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.11	0.14	-9999	-0.24	272	272
lamellipodium assembly	-0.12	0.13	-9999	-0.24	264	264
RET51/GFRalpha1/GDNF/SHC	-0.1	0.13	-9999	-0.23	262	262
PIK3CA	0.01	0.018	-9999	-0.41	1	1
RET9/GFRalpha1/GDNF/SHC	-0.09	0.11	-9999	-0.21	256	256
RET9/GFRalpha1/GDNF/Shank3	-0.09	0.11	-9999	-0.21	256	256
MAPK3	-0.075	0.11	-9999	-0.34	30	30
DOK1	0.011	0	-9999	-10000	0	0
DOK6	-0.073	0.17	-9999	-0.41	108	108
PXN	0.011	0	-9999	-10000	0	0
neurite development	-0.082	0.12	-9999	-0.27	95	95
DOK5	-0.028	0.12	-9999	-0.41	51	51
GFRA1	-0.19	0.21	-9999	-0.41	257	257
MAPK8	-0.084	0.13	-9999	-0.4	33	33
HRAS/GTP	-0.11	0.12	-9999	-0.23	262	262
tube development	-0.078	0.11	-9999	-0.19	256	256
MAPK1	-0.075	0.11	-9999	-0.34	30	30
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.081	0.11	-9999	-0.2	255	255
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
PDLIM7	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.13	0.16	-9999	-0.4	98	98
SHC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.13	-9999	-0.23	262	262
RET51/GFRalpha1/GDNF/Dok5	-0.12	0.16	-9999	-0.26	273	273
PRKCA	-0.017	0.1	-9999	-0.41	36	36
HRAS/GDP	0.008	0	-9999	-10000	0	0
CREB1	-0.1	0.14	-9999	-0.25	255	255
PIK3R1	0.007	0.04	-9999	-0.41	5	5
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.084	0.12	-9999	-0.2	255	255
RET51/GFRalpha1/GDNF/Grb7	-0.11	0.14	-9999	-0.23	265	265
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.024	0.11	-9999	-0.37	49	49
DOK4	0.011	0	-9999	-10000	0	0
JNK cascade	-0.075	0.13	-9999	-0.38	36	36
RET9/GFRalpha1/GDNF/FRS2	-0.09	0.11	-9999	-0.21	256	256
SHANK3	0.011	0	-9999	-10000	0	0
RASA1	0.007	0.04	-9999	-0.41	5	5
NCK1	0.009	0.025	-9999	-0.41	2	2
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.082	0.11	-9999	-0.2	255	255
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.09	0.12	-9999	-0.21	261	261
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.094	0.13	-9999	-0.22	262	262
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.094	0.14	-9999	-0.44	29	29
PI3K	-0.16	0.21	-9999	-0.36	264	264
SOS1	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.078	0.11	-9999	-0.19	256	256
GRB10	0.01	0.018	-9999	-0.41	1	1
activation of MAPKK activity	-0.082	0.11	-9999	-0.31	29	29
RET51/GFRalpha1/GDNF/FRS2	-0.1	0.13	-9999	-0.23	262	262
GAB1	0.008	0.036	-9999	-0.41	4	4
IRS1	-0.031	0.13	-9999	-0.41	54	54
IRS2	-0.042	0.14	-9999	-0.41	69	69
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.096	0.14	-9999	-0.24	172	172
RET51/GFRalpha1/GDNF/PKC alpha	-0.12	0.15	-9999	-0.24	273	273
GRB2	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GDNF	0.003	0.025	-9999	-0.33	3	3
RAC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.16	-9999	-0.26	276	276
Rac1/GTP	-0.15	0.15	-9999	-0.28	264	264
RET9/GFRalpha1/GDNF	-0.11	0.13	-9999	-0.24	257	257
GFRalpha1/GDNF	-0.13	0.15	-9999	-0.29	257	257

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.089	0.2	-10000	0	-0.39	116	116
PTK2B	0.011	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.13	0.32	-10000	0	-0.8	83	83
EDN1	-0.002	0.089	-10000	0	-0.39	11	11
EDN3	-0.099	0.17	-10000	0	-0.36	160	160
EDN2	-0.042	0.12	-10000	0	-0.33	85	85
HRAS/GDP	-0.12	0.21	-10000	0	-0.42	137	137
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.084	0.18	-10000	0	-0.35	129	129
ADCY4	-0.11	0.19	-10000	0	-0.39	138	138
ADCY5	-0.14	0.2	-10000	0	-0.4	163	163
ADCY6	-0.1	0.18	-10000	0	-0.37	134	134
ADCY7	-0.1	0.18	-10000	0	-0.37	134	134
ADCY1	-0.12	0.2	-10000	0	-0.39	136	136
ADCY2	-0.22	0.23	-10000	0	-0.46	210	210
ADCY3	-0.11	0.19	-10000	0	-0.38	134	134
ADCY8	-0.11	0.18	-10000	0	-0.38	134	134
ADCY9	-0.13	0.22	-10000	0	-0.42	156	156
arachidonic acid secretion	-0.17	0.28	-10000	0	-0.46	222	222
ETB receptor/Endothelin-1/Gq/GTP	-0.067	0.15	-10000	0	-0.29	139	139
GNAO1	-0.1	0.18	-10000	0	-0.41	143	143
HRAS	0.009	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.059	0.21	-10000	0	-0.36	116	116
ETA receptor/Endothelin-1/Gs/GTP	-0.089	0.22	-10000	0	-0.4	134	134
mol:GTP	-0.002	0.005	-10000	0	-10000	0	0
COL3A1	-0.097	0.22	-10000	0	-0.43	118	118
EDNRB	-0.083	0.18	-10000	0	-0.41	124	124
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.13	0.26	-10000	0	-0.47	162	162
CYSLTR1	-0.094	0.21	-10000	0	-0.43	104	104
SLC9A1	-0.058	0.11	-10000	0	-0.23	116	116
mol:GDP	-0.13	0.22	-10000	0	-0.44	141	141
SLC9A3	-0.14	0.3	-10000	0	-0.62	133	133
RAF1	-0.16	0.24	-10000	0	-0.42	208	208
JUN	-0.1	0.26	-10000	0	-0.66	80	80
JAK2	-0.093	0.2	-10000	0	-0.38	135	135
mol:IP3	-0.09	0.18	-10000	0	-0.39	101	101
ETA receptor/Endothelin-1	-0.086	0.26	-10000	0	-0.43	145	145
PLCB1	0.006	0.032	-10000	0	-0.41	3	3
PLCB2	0.008	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.16	0.19	-10000	0	-0.33	284	284
FOS	-0.29	0.43	-10000	0	-0.87	179	179
Gai/GDP	-0.19	0.34	-10000	0	-0.73	144	144
CRK	0.011	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.14	0.25	-10000	0	-0.47	160	160
BCAR1	0.011	0	-10000	0	-10000	0	0
PRKCB1	-0.091	0.17	-10000	0	-0.38	104	104
GNAQ	0.007	0.026	-10000	0	-0.41	2	2
GNAZ	-0.002	0.073	-10000	0	-0.41	17	17
GNAL	-0.051	0.15	-10000	0	-0.41	80	80
Gs family/GDP	-0.16	0.2	-10000	0	-0.42	167	167
ETA receptor/Endothelin-1/Gq/GTP	-0.098	0.21	-10000	0	-0.38	149	149
MAPK14	-0.05	0.13	-10000	0	-0.3	79	79
TRPC6	-0.14	0.34	-10000	0	-0.86	83	83
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.051	-10000	0	-0.41	8	8
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.059	0.14	-10000	0	-0.3	104	104
ETB receptor/Endothelin-2	-0.085	0.15	-10000	0	-0.28	184	184
ETB receptor/Endothelin-3	-0.12	0.16	-10000	0	-0.28	253	253
ETB receptor/Endothelin-1	-0.056	0.15	-10000	0	-0.3	131	131
MAPK3	-0.26	0.38	-10000	0	-0.74	190	190
MAPK1	-0.26	0.38	-10000	0	-0.74	190	190
Rac1/GDP	-0.12	0.21	-10000	0	-0.41	137	137
cAMP biosynthetic process	-0.19	0.24	-10000	0	-0.44	215	215
MAPK8	-0.13	0.3	-10000	0	-0.7	93	93
SRC	0.011	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.087	0.16	-10000	0	-0.36	106	106
p130Cas/CRK/Src/PYK2	-0.11	0.23	-10000	0	-0.52	103	103
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.12	0.21	-10000	0	-0.41	137	137
COL1A2	-0.13	0.25	-10000	0	-0.52	122	122
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.12	0.18	-10000	0	-0.32	224	224
mol:DAG	-0.09	0.18	-10000	0	-0.39	101	101
MAP2K2	-0.2	0.3	-10000	0	-0.55	200	200
MAP2K1	-0.2	0.3	-10000	0	-0.55	200	200
EDNRA	-0.13	0.24	-10000	0	-0.47	166	166
positive regulation of muscle contraction	-0.071	0.17	-10000	0	-0.37	91	91
Gq family/GDP	-0.13	0.19	-10000	0	-0.43	118	118
HRAS/GTP	-0.12	0.21	-10000	0	-0.4	151	151
PRKCH	-0.086	0.18	-10000	0	-0.39	97	97
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.098	0.19	-10000	0	-0.4	112	112
PRKCB	-0.097	0.19	-10000	0	-0.41	107	107
PRKCE	-0.084	0.17	-10000	0	-0.37	101	101
PRKCD	-0.086	0.17	-10000	0	-0.38	99	99
PRKCG	-0.11	0.18	-10000	0	-0.38	121	121
regulation of vascular smooth muscle contraction	-0.34	0.5	-10000	0	-1	179	179
PRKCQ	-0.1	0.18	-10000	0	-0.38	127	127
PLA2G4A	-0.19	0.31	-10000	0	-0.5	222	222
GNA14	-0.033	0.13	-10000	0	-0.41	54	54
GNA15	0.004	0.039	-10000	0	-0.34	7	7
GNA12	0.011	0	-10000	0	-10000	0	0
GNA11	-0.001	0.062	-10000	0	-0.41	12	12
Rac1/GTP	-0.059	0.21	0.17	112	-0.36	116	228
MMP1	-0.048	0.15	0.27	9	-0.23	141	150

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.19	0.44	-10000	0	-0.84	168	168
NCK1/PAK1/Dok-R	-0.12	0.18	-10000	0	-0.4	168	168
NCK1/Dok-R	-0.26	0.51	-10000	0	-1	168	168
PIK3CA	0.011	0.018	-10000	0	-0.41	1	1
mol:beta2-estradiol	0.043	0.095	0.23	110	-10000	0	110
RELA	0.011	0	-10000	0	-10000	0	0
SHC1	0.011	0.002	-10000	0	-10000	0	0
Rac/GDP	0.008	0	-10000	0	-10000	0	0
F2	0.026	0.14	0.25	110	-0.34	40	150
TNIP2	0.011	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.28	0.45	-10000	0	-0.93	168	168
FN1	0.007	0.04	-10000	0	-0.41	5	5
PLD2	-0.28	0.53	-10000	0	-1	168	168
PTPN11	0.011	0	-10000	0	-10000	0	0
GRB14	-0.11	0.16	-10000	0	-0.33	196	196
ELK1	-0.24	0.47	-10000	0	-0.93	168	168
GRB7	-0.011	0.084	-10000	0	-0.33	34	34
PAK1	0.011	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.3	0.47	-10000	0	-0.97	168	168
CDKN1A	-0.11	0.3	-10000	0	-0.59	129	129
ITGA5	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.26	0.51	-10000	0	-1	168	168
CRK	0.011	0	-10000	0	-10000	0	0
mol:NO	-0.13	0.33	-10000	0	-0.62	168	168
PLG	-0.3	0.53	-10000	0	-1	168	168
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.22	0.4	-10000	0	-0.8	168	168
GRB2	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
ANGPT2	-0.06	0.2	-10000	0	-0.55	37	37
BMX	-0.3	0.54	-10000	0	-1.1	168	168
ANGPT1	-0.23	0.48	-10000	0	-1.2	110	110
tube development	-0.13	0.34	-10000	0	-0.61	166	166
ANGPT4	0	0.045	-10000	0	-0.39	7	7
response to hypoxia	-0.017	0.032	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.32	0.56	-10000	0	-1.1	168	168
alpha5/beta1 Integrin	0.016	0	-10000	0	-10000	0	0
FGF2	-0.22	0.21	-10000	0	-0.41	295	295
STAT5A (dimer)	-0.15	0.38	-10000	0	-0.7	157	157
mol:L-citrulline	-0.13	0.33	-10000	0	-0.62	168	168
AGTR1	-0.085	0.17	-10000	0	-0.41	122	122
MAPK14	-0.28	0.54	-10000	0	-1.1	168	168
Tie2/SHP2	-0.21	0.4	-10000	0	-1.1	92	92
TEK	-0.2	0.46	-10000	0	-1.2	92	92
RPS6KB1	-0.19	0.42	-10000	0	-0.8	168	168
Angiotensin II/AT1	-0.057	0.12	-10000	0	-0.28	122	122
Tie2/Ang1/GRB2	-0.29	0.55	-10000	0	-1.1	168	168
MAPK3	-0.25	0.48	-10000	0	-0.95	168	168
MAPK1	-0.25	0.48	-10000	0	-0.95	168	168
Tie2/Ang1/GRB7	-0.29	0.55	-10000	0	-1.1	168	168
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	-0.28	0.53	-10000	0	-1	168	168
PI3K	-0.24	0.5	-10000	0	-0.96	168	168
FES	-0.27	0.54	-10000	0	-1	168	168
Crk/Dok-R	-0.26	0.51	-10000	0	-1	168	168
Tie2/Ang1/ABIN2	-0.29	0.55	-10000	0	-1.1	168	168
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.17	0.39	-10000	0	-0.74	168	168
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.19	0.42	-10000	0	-0.8	168	168
Tie2/Ang2	-0.19	0.45	-10000	0	-0.86	152	152
Tie2/Ang1	-0.31	0.58	-10000	0	-1.1	168	168
FOXO1	-0.16	0.4	-10000	0	-0.75	168	168
ELF1	-0.006	0.054	-10000	0	-0.44	4	4
ELF2	-0.28	0.53	-10000	0	-1	168	168
mol:Choline	-0.26	0.5	-10000	0	-0.99	168	168
cell migration	-0.07	0.1	-10000	0	-0.22	168	168
FYN	-0.15	0.38	-10000	0	-0.7	164	164
DOK2	0.008	0.031	-10000	0	-0.35	4	4
negative regulation of cell cycle	-0.094	0.28	-10000	0	-0.53	129	129
ETS1	-0.031	0.095	-10000	0	-0.22	110	110
PXN	-0.14	0.35	-10000	0	-0.66	168	168
ITGB1	0.011	0	-10000	0	-10000	0	0
NOS3	-0.15	0.37	-10000	0	-0.7	168	168
RAC1	0.011	0	-10000	0	-10000	0	0
TNF	-0.074	0.15	-10000	0	-0.28	167	167
MAPKKK cascade	-0.26	0.5	-10000	0	-0.99	168	168
RASA1	0.007	0.04	-10000	0	-0.41	5	5
Tie2/Ang1/Shc	-0.29	0.55	-10000	0	-1.1	168	168
NCK1	0.009	0.025	-10000	0	-0.41	2	2
vasculogenesis	-0.11	0.3	-10000	0	-0.55	168	168
mol:Phosphatidic acid	-0.26	0.5	-10000	0	-0.99	168	168
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.13	0.33	-10000	0	-0.62	168	168
Rac1/GTP	-0.23	0.35	-10000	0	-0.75	168	168
MMP2	-0.29	0.54	-10000	0	-1.1	168	168

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.12	0.19	-9999	-0.43	149	149
PDGF/PDGFRA/CRKL	-0.069	0.13	-9999	-0.28	149	149
positive regulation of JUN kinase activity	-0.036	0.098	-9999	-0.2	149	149
CRKL	0.011	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.076	0.13	-9999	-0.29	150	150
AP1	-0.29	0.39	-9999	-0.86	167	167
mol:IP3	-0.08	0.14	-9999	-0.3	149	149
PLCG1	-0.08	0.14	-9999	-0.3	149	149
PDGF/PDGFRA/alphaV Integrin	-0.069	0.13	-9999	-0.28	149	149
RAPGEF1	0.011	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
mol:Ca2+	-0.08	0.14	-9999	-0.3	149	149
CAV3	0.002	0.015	-9999	-0.33	1	1
CAV1	-0.062	0.16	-9999	-0.41	94	94
SHC/Grb2/SOS1	-0.036	0.099	-9999	-0.2	149	149
PDGF/PDGFRA/Shf	-0.073	0.14	-9999	-0.29	151	151
FOS	-0.27	0.4	-9999	-0.85	167	167
JUN	-0.026	0.045	-9999	-0.34	7	7
oligodendrocyte development	-0.069	0.13	-9999	-0.28	149	149
GRB2	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
mol:DAG	-0.08	0.14	-9999	-0.3	149	149
PDGF/PDGFRA	-0.12	0.19	-9999	-0.43	149	149
actin cytoskeleton reorganization	-0.069	0.13	-9999	-0.28	149	149
SRF	0.025	0.011	-9999	-10000	0	0
SHC1	0.011	0	-9999	-10000	0	0
PI3K	-0.051	0.11	-9999	-0.23	152	152
PDGF/PDGFRA/Crk/C3G	-0.049	0.11	-9999	-0.23	149	149
JAK1	-0.069	0.14	-9999	-0.29	149	149
ELK1/SRF	-0.041	0.11	-9999	-0.22	149	149
SHB	0.011	0	-9999	-10000	0	0
SHF	0.006	0.047	-9999	-0.41	7	7
CSNK2A1	0.021	0.024	-9999	-10000	0	0
GO:0007205	-0.09	0.15	-9999	-0.34	149	149
SOS1	0.011	0	-9999	-10000	0	0
Ras protein signal transduction	-0.036	0.098	-9999	-0.2	149	149
PDGF/PDGFRA/SHB	-0.069	0.13	-9999	-0.28	149	149
PDGF/PDGFRA/Caveolin-1	-0.12	0.19	-9999	-0.35	191	191
ITGAV	0.011	0	-9999	-10000	0	0
ELK1	-0.081	0.14	-9999	-0.29	149	149
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PDGF/PDGFRA/Crk	-0.069	0.13	-9999	-0.28	149	149
JAK-STAT cascade	-0.069	0.13	-9999	-0.28	149	149
cell proliferation	-0.073	0.14	-9999	-0.29	151	151

×

p75(NTR)-mediated signaling

Figure S9. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S9. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.016	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.17	0.18	-10000	0	-0.31	303	303
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.085	0.15	-10000	0	-0.36	75	75
NGF (dimer)/p75(NTR)/BEX1	-0.16	0.2	-10000	0	-0.33	278	278
NT-4/5 (dimer)/p75(NTR)	-0.096	0.14	-10000	0	-0.28	205	205
IKBKB	0.011	0	-10000	0	-10000	0	0
AKT1	-0.085	0.14	-10000	0	-0.38	66	66
IKBKG	0.011	0	-10000	0	-10000	0	0
BDNF	-0.044	0.12	-10000	0	-0.33	88	88
MGDIs/NGR/p75(NTR)/LINGO1	-0.065	0.12	-10000	0	-0.23	192	192
FURIN	0.011	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.093	0.13	-10000	0	-0.22	260	260
LINGO1	0.006	0.04	-10000	0	-0.34	7	7
Sortilin/TRAF6/NRIF	-0.002	0.016	-10000	0	-10000	0	0
proBDNF (dimer)	-0.044	0.12	-10000	0	-0.33	88	88
NTRK1	0.001	0.058	-10000	0	-0.37	13	13
RTN4R	0.01	0.018	-10000	0	-0.41	1	1
neuron apoptosis	-0.093	0.14	-10000	0	-0.33	82	82
IRAK1	0.011	0	-10000	0	-10000	0	0
SHC1	-0.11	0.17	-10000	0	-0.29	236	236
ARHGDIA	0.011	0	-10000	0	-10000	0	0
RhoA/GTP	0.008	0	-10000	0	-10000	0	0
Gamma Secretase	0.03	0.024	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.15	0.19	-10000	0	-0.29	296	296
MAGEH1	-0.09	0.18	-10000	0	-0.41	130	130
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.2	0.2	-10000	0	-0.32	359	359
Mammalian IAPs/DIABLO	0.024	0.029	-10000	0	-0.2	8	8
proNGF (dimer)	-0.078	0.17	-10000	0	-0.41	115	115
MAGED1	0.009	0.025	-10000	0	-0.41	2	2
APP	0.011	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.006	0.07	-10000	0	-0.33	24	24
ZNF274	0.011	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.089	0.14	-10000	0	-0.24	235	235
NGF	-0.078	0.17	-10000	0	-0.41	115	115
cell cycle arrest	-0.08	0.13	0.14	40	-0.36	64	104
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.09	0.15	-10000	0	-0.25	235	235
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.072	0.12	-10000	0	-0.23	205	205
NCSTN	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.12	0.17	-10000	0	-0.29	240	240
PSENEN	0.011	0	-10000	0	-10000	0	0
mol:ceramide	-0.095	0.15	-10000	0	-0.25	235	235
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.071	0.13	-10000	0	-0.34	64	64
p75(NTR)/beta APP	-0.084	0.14	-10000	0	-0.28	185	185
BEX1	-0.074	0.17	-10000	0	-0.41	110	110
mol:GDP	-0.12	0.17	-10000	0	-0.29	236	236
NGF (dimer)	-0.078	0.14	-10000	0	-0.25	179	179
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.051	0.11	-10000	0	-0.2	185	185
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
RAC1/GTP	-0.095	0.14	-10000	0	-0.25	235	235
MYD88	0.011	0	-10000	0	-10000	0	0
CHUK	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.12	0.17	-10000	0	-0.29	240	240
RHOB	0.009	0.025	-10000	0	-0.41	2	2
RHOA	0.011	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.027	0.091	-10000	0	-0.22	102	102
NT3 (dimer)	-0.018	0.1	-10000	0	-0.4	38	38
TP53	-0.058	0.1	-10000	0	-0.31	13	13
PRDM4	-0.095	0.15	-10000	0	-0.26	235	235
BDNF (dimer)	-0.089	0.14	-10000	0	-0.29	117	117
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
SORT1	0.011	0	-10000	0	-10000	0	0
activation of caspase activity	-0.1	0.13	-10000	0	-0.38	66	66
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.095	0.15	-10000	0	-0.26	235	235
RHOC	0.011	0	-10000	0	-10000	0	0
XIAP	0.011	0	-10000	0	-10000	0	0
MAPK10	-0.13	0.18	-10000	0	-0.4	132	132
DIABLO	0.011	0	-10000	0	-10000	0	0
SMPD2	-0.095	0.15	-10000	0	-0.26	235	235
APH1B	0.006	0.047	-10000	0	-0.41	7	7
APH1A	0.011	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.11	0.17	-10000	0	-0.29	235	235
PSEN1	0.011	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.1	0.16	-10000	0	-0.3	208	208
MAPK8	-0.095	0.15	-10000	0	-0.34	88	88
MAPK9	-0.093	0.15	-10000	0	-0.36	78	78
APAF1	0.011	0	-10000	0	-10000	0	0
NTF3	-0.018	0.1	-10000	0	-0.4	38	38
NTF4	-0.006	0.07	-10000	0	-0.33	24	24
NDN	-0.19	0.21	-10000	0	-0.41	265	265
RAC1/GDP	0.008	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.094	0.12	-10000	0	-0.35	66	66
p75 CTF/Sortilin/TRAF6/NRIF	0.028	0	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.11	0.17	-10000	0	-0.29	240	240
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.066	0.11	-10000	0	-0.19	184	184
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.077	0.11	-10000	0	-0.21	184	184
PRKACB	0.006	0.044	-10000	0	-0.41	6	6
proBDNF (dimer)/p75 ECD	-0.021	0.086	-10000	0	-0.22	88	88
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.004	0.055	-10000	0	-0.39	10	10
BIRC2	0.011	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.19	0.2	0.15	17	-0.36	262	279
BAD	-0.11	0.16	-10000	0	-0.34	130	130
RIPK2	0.011	0	-10000	0	-10000	0	0
NGFR	-0.13	0.2	-10000	0	-0.41	185	185
CYCS	-0.084	0.14	-10000	0	-0.38	65	65
ADAM17	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.095	0.15	-10000	0	-0.26	235	235
BCL2L11	-0.11	0.16	-10000	0	-0.34	130	130
BDNF (dimer)/p75(NTR)	-0.12	0.15	-10000	0	-0.27	260	260
PI3K	-0.097	0.15	-10000	0	-0.26	239	239
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.095	0.15	-10000	0	-0.26	235	235
NDNL2	0.011	0	-10000	0	-10000	0	0
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.14	0.19	-10000	0	-0.35	236	236
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.096	0.15	-10000	0	-0.26	237	237
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.023	-10000	0	-0.37	2	2
PLG	-0.032	0.12	-10000	0	-0.4	55	55
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.12	0.16	-10000	0	-0.3	192	192
SQSTM1	0.011	0	-10000	0	-10000	0	0
NGFRAP1	0.006	0.044	-10000	0	-0.41	6	6
CASP3	-0.1	0.16	-10000	0	-0.32	130	130
E2F1	-0.053	0.13	-10000	0	-0.33	102	102
CASP9	0.011	0	-10000	0	-10000	0	0
IKK complex	-0.093	0.13	-10000	0	-0.31	121	121
NGF (dimer)/TRKA	-0.053	0.13	-10000	0	-0.28	126	126
MMP7	-0.058	0.14	-10000	0	-0.36	101	101
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.083	0.14	-10000	0	-0.24	235	235
MMP3	-0.05	0.13	-10000	0	-0.33	96	96
APAF-1/Caspase 9	-0.072	0.094	-10000	0	-0.28	65	65

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.053	0.17	-10000	0	-0.59	36	36
IHH	-0.13	0.2	-10000	0	-0.39	189	189
SHH Np/Cholesterol/GAS1	-0.15	0.13	-10000	0	-0.23	358	358
LRPAP1	0.011	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.14	0.13	0.23	358	-10000	0	358
SMO/beta Arrestin2	-0.051	0.15	-10000	0	-0.42	26	26
SMO	-0.059	0.16	-10000	0	-0.32	137	137
AKT1	-0.017	0.095	-10000	0	-0.47	6	6
ARRB2	0.011	0	-10000	0	-10000	0	0
BOC	-0.003	0.075	-10000	0	-0.41	18	18
ADRBK1	0.011	0	-10000	0	-10000	0	0
heart looping	-0.059	0.16	-10000	0	-0.31	137	137
STIL	-0.048	0.12	-10000	0	-0.34	32	32
DHH N/PTCH2	-0.024	0.11	-10000	0	-0.3	70	70
DHH N/PTCH1	-0.059	0.14	-10000	0	-0.39	38	38
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
DHH	-0.024	0.12	-10000	0	-0.41	44	44
PTHLH	-0.068	0.21	-10000	0	-0.65	36	36
determination of left/right symmetry	-0.059	0.16	-10000	0	-0.31	137	137
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
skeletal system development	-0.067	0.21	-10000	0	-0.64	36	36
IHH N/Hhip	-0.079	0.13	-10000	0	-0.26	157	157
DHH N/Hhip	-0.024	0.099	-10000	0	-0.26	77	77
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.059	0.16	-10000	0	-0.31	137	137
pancreas development	-0.012	0.087	-10000	0	-0.34	35	35
HHAT	0.008	0.036	-10000	0	-0.41	4	4
PI3K	0.013	0.031	-10000	0	-0.28	6	6
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.26	0.2	-10000	0	-0.41	346	346
somite specification	-0.059	0.16	-10000	0	-0.31	137	137
SHH Np/Cholesterol/PTCH1	-0.051	0.12	-10000	0	-0.36	25	25
SHH Np/Cholesterol/PTCH2	-0.017	0.079	-10000	0	-0.18	99	99
SHH Np/Cholesterol/Megalin	-0.067	0.1	-10000	0	-0.18	238	238
SHH	-0.015	0.082	-10000	0	-0.22	73	73
catabolic process	-0.053	0.14	-10000	0	-0.35	36	36
SMO/Vitamin D3	-0.048	0.14	-10000	0	-0.4	26	26
SHH Np/Cholesterol/Hhip	-0.017	0.075	-10000	0	-0.17	104	104
LRP2	-0.11	0.16	-10000	0	-0.33	193	193
receptor-mediated endocytosis	-0.074	0.14	-10000	0	-0.32	79	79
SHH Np/Cholesterol/BOC	-0.012	0.073	-10000	0	-0.17	88	88
SHH Np/Cholesterol/CDO	-0.029	0.096	-10000	0	-0.2	118	118
mesenchymal cell differentiation	0.017	0.074	0.17	104	-10000	0	104
mol:Vitamin D3	-0.04	0.12	-10000	0	-0.36	25	25
IHH N/PTCH2	-0.079	0.14	-10000	0	-0.28	148	148
CDON	-0.035	0.13	-10000	0	-0.41	59	59
IHH N/PTCH1	-0.034	0.15	-10000	0	-0.36	36	36
Megalin/LRPAP1	-0.067	0.11	-10000	0	-0.22	193	193
PTCH2	-0.012	0.096	-10000	0	-0.41	30	30
SHH Np/Cholesterol	-0.012	0.06	-10000	0	-0.16	73	73
PTCH1	-0.053	0.14	-10000	0	-0.36	36	36
HHIP	-0.012	0.087	-10000	0	-0.34	35	35

×

Integrins in angiogenesis

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.002	0.071	-9999	-0.28	33	33
alphaV beta3 Integrin	-0.16	0.16	-9999	-0.28	322	322
PTK2	-0.13	0.19	-9999	-0.42	134	134
IGF1R	-0.005	0.081	-9999	-0.41	21	21
PI4KB	0.011	0	-9999	-10000	0	0
MFGE8	0.009	0.025	-9999	-0.41	2	2
SRC	0.011	0	-9999	-10000	0	0
CDKN1B	-0.14	0.22	-9999	-0.59	88	88
VEGFA	0.011	0	-9999	-10000	0	0
ILK	-0.12	0.19	-9999	-0.56	71	71
ROCK1	0.011	0	-9999	-10000	0	0
AKT1	-0.1	0.18	-9999	-0.52	71	71
PTK2B	-0.021	0.1	-9999	-0.38	16	16
alphaV/beta3 Integrin/JAM-A	-0.15	0.16	-9999	-0.4	118	118
CBL	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.029	0.099	-9999	-0.23	103	103
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.044	0.14	-9999	-0.26	136	136
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.039	0.12	-9999	-0.35	31	31
alphaV/beta3 Integrin/Syndecan-1	-0.078	0.12	-9999	-0.21	240	240
PI4KA	0.011	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.18	0.18	-9999	-0.42	156	156
PI4 Kinase	0.016	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
alphaV/beta3 Integrin/Osteopontin	-0.079	0.12	-9999	-0.21	241	241
RPS6KB1	-0.15	0.18	-9999	-0.39	156	156
TLN1	0.011	0	-9999	-10000	0	0
MAPK3	-0.29	0.28	-9999	-0.5	321	321
GPR124	-0.089	0.18	-9999	-0.41	129	129
MAPK1	-0.29	0.28	-9999	-0.5	321	321
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
alphaV/beta3 Integrin/Tumstatin	-0.053	0.12	-9999	-0.24	152	152
cell adhesion	-0.034	0.095	-9999	-0.23	100	100
ANGPTL3	0.004	0.025	-9999	-0.33	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	0.007	0.06	-9999	-0.23	33	33
IGF-1R heterotetramer	-0.005	0.081	-9999	-0.41	21	21
Rac1/GDP	0.008	0	-9999	-10000	0	0
TGFBR2	0.002	0.062	-9999	-0.41	12	12
ITGB3	-0.068	0.16	-9999	-0.41	102	102
IGF1	-0.067	0.16	-9999	-0.41	101	101
RAC1	0.011	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.081	0.15	-9999	-0.27	190	190
apoptosis	0.011	0	-9999	-10000	0	0
CD47	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.024	0.097	-9999	-0.23	102	102
VCL	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.072	0.15	-9999	-0.28	168	168
CSF1	0.003	0.057	-9999	-0.41	10	10
PIK3C2A	-0.12	0.19	-9999	-0.56	71	71
PI4 Kinase/Pyk2	-0.14	0.14	-9999	-0.35	131	131
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.027	0.11	-9999	-0.23	118	118
FAK1/Vinculin	-0.099	0.15	-9999	-0.34	121	121
alphaV beta3/Integrin/ppsTEM5	-0.081	0.15	-9999	-0.28	190	190
RHOA	0.011	0	-9999	-10000	0	0
VTN	-0.047	0.14	-9999	-0.41	74	74
BCAR1	0.011	0	-9999	-10000	0	0
FGF2	-0.22	0.21	-9999	-0.41	295	295
F11R	-0.14	0.15	-9999	-0.28	296	296
alphaV/beta3 Integrin/Lactadherin	-0.025	0.1	-9999	-0.23	102	102
alphaV/beta3 Integrin/TGFBR2	-0.029	0.11	-9999	-0.25	105	105
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.024	0.03	-9999	-0.2	10	10
HSP90AA1	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.021	0.088	-9999	-0.2	102	102
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.007	0.04	-9999	-0.41	5	5
alphaV/beta3 Integrin/Pyk2	-0.02	0.1	-9999	-0.38	16	16
SDC1	-0.084	0.15	-9999	-0.33	153	153
VAV3	-0.011	0.073	-9999	-0.2	10	10
PTPN11	0.011	0	-9999	-10000	0	0
IRS1	-0.031	0.13	-9999	-0.41	54	54
FAK1/Paxillin	-0.099	0.15	-9999	-0.34	121	121
cell migration	-0.086	0.14	-9999	-0.31	116	116
ITGAV	0.011	0	-9999	-10000	0	0
PI3K	-0.14	0.14	-9999	-0.36	121	121
SPP1	-0.086	0.15	-9999	-0.33	155	155
KDR	-0.015	0.1	-9999	-0.41	33	33
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.011	0	-9999	-10000	0	0
COL4A3	-0.039	0.13	-9999	-0.39	66	66
angiogenesis	-0.29	0.28	-9999	-0.5	322	322
Rac1/GTP	-0.004	0.067	-9999	-0.3	1	1
EDIL3	-0.072	0.17	-9999	-0.41	107	107
cell proliferation	-0.029	0.11	-9999	-0.24	105	105

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.004	0.077	-10000	0	-0.41	19	19
ANTXR2	-0.13	0.2	-10000	0	-0.41	179	179
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.019	0.028	-10000	0	-0.057	183	183
monocyte activation	-0.028	0.11	-10000	0	-0.41	41	41
MAP2K2	-0.007	0.011	-10000	0	-10000	0	0
MAP2K1	-0.016	0.023	-10000	0	-10000	0	0
MAP2K7	-0.016	0.023	-10000	0	-0.078	15	15
MAP2K6	-0.035	0.055	-10000	0	-0.16	69	69
CYAA	-0.064	0.11	-10000	0	-0.21	183	183
MAP2K4	-0.016	0.025	-10000	0	-0.25	1	1
IL1B	-0.011	0.042	-10000	0	-0.14	30	30
Channel	-0.067	0.12	-10000	0	-0.23	183	183
NLRP1	-0.026	0.053	-10000	0	-0.24	26	26
CALM1	0.011	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.021	0.03	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.019	0.028	0.057	183	-10000	0	183
MAPK3	-0.016	0.023	-10000	0	-10000	0	0
MAPK1	-0.016	0.023	-10000	0	-10000	0	0
PGR	-0.077	0.1	-10000	0	-0.23	164	164
PA/Cellular Receptors	-0.075	0.13	-10000	0	-0.25	183	183
apoptosis	-0.019	0.028	-10000	0	-0.057	183	183
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.064	0.11	-10000	0	-0.22	183	183
macrophage activation	-0.003	0.026	-10000	0	-10000	0	0
TNF	-0.032	0.11	-10000	0	-0.33	68	68
VCAM1	-0.028	0.11	-10000	0	-0.41	41	41
platelet activation	-0.021	0.03	-10000	0	-10000	0	0
MAPKKK cascade	0.013	0.031	0.085	32	-10000	0	32
IL18	-0.012	0.043	-10000	0	-0.14	35	35
negative regulation of macrophage activation	-0.019	0.028	-10000	0	-0.057	183	183
LEF	-0.019	0.028	-10000	0	-0.058	183	183
CASP1	-0.021	0.036	-10000	0	-0.12	41	41
mol:cAMP	-0.021	0.03	-10000	0	-10000	0	0
necrosis	-0.019	0.028	-10000	0	-0.057	183	183
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.063	0.11	-10000	0	-0.21	183	183
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.023	0.09	-10000	0	-0.21	101	101
regulation of S phase of mitotic cell cycle	-0.018	0.088	-10000	0	-0.2	96	96
GNAO1	-0.1	0.18	-10000	0	-0.41	143	143
HRAS	0.01	0.002	-10000	0	-10000	0	0
SHBG/T-DHT	0.005	0.024	-10000	0	-0.24	5	5
PELP1	0.01	0.002	-10000	0	-10000	0	0
AKT1	0.009	0.001	-10000	0	-10000	0	0
MAP2K1	-0.031	0.092	-10000	0	-0.27	33	33
T-DHT/AR	-0.044	0.11	-10000	0	-0.29	93	93
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.007	167	167
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.051	-10000	0	-0.41	8	8
mol:GDP	-0.059	0.14	-10000	0	-0.35	93	93
cell proliferation	-0.1	0.2	-10000	0	-0.38	167	167
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
FOS	-0.22	0.37	-10000	0	-0.77	167	167
mol:Ca2+	-0.024	0.03	-10000	0	-0.061	175	175
MAPK3	-0.071	0.15	-10000	0	-0.26	167	167
MAPK1	-0.049	0.1	-10000	0	-0.2	167	167
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
mol:IP3	-0.001	0.002	-10000	0	-0.004	167	167
cAMP biosynthetic process	0.008	0.03	0.092	6	-0.2	5	11
GNG2	0.003	0.056	-10000	0	-0.4	10	10
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	167	167
HRAS/GTP	-0.041	0.072	-10000	0	-0.2	93	93
actin cytoskeleton reorganization	-0.002	0.018	-10000	0	-0.18	6	6
SRC	0.01	0.002	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	167	167
PI3K	0.012	0.026	-10000	0	-0.23	6	6
apoptosis	0.11	0.2	0.4	167	-10000	0	167
T-DHT/AR/PELP1	-0.031	0.095	-10000	0	-0.24	93	93
HRAS/GDP	-0.056	0.13	-10000	0	-0.33	93	93
CREB1	-0.12	0.21	-10000	0	-0.43	167	167
RAC1-CDC42/GTP	-0.002	0.019	-10000	0	-0.18	6	6
AR	-0.062	0.16	-10000	0	-0.41	93	93
GNB1	0.011	0	-10000	0	-10000	0	0
RAF1	-0.028	0.085	-10000	0	-0.25	33	33
RAC1-CDC42/GDP	-0.049	0.12	-10000	0	-0.31	93	93
T-DHT/AR/PELP1/Src	-0.024	0.086	-10000	0	-0.21	93	93
MAP2K2	-0.031	0.092	-10000	0	-0.27	33	33
T-DHT/AR/PELP1/Src/PI3K	-0.018	0.088	-10000	0	-0.21	96	96
GNAZ	-0.002	0.073	-10000	0	-0.41	17	17
SHBG	0.007	0.04	-10000	0	-0.41	5	5
Gi family/GNB1/GNG2/GDP	-0.072	0.16	-10000	0	-0.32	147	147
mol:T-DHT	-0.001	0.001	-10000	0	-0.003	134	134
RAC1	0.011	0	-10000	0	-10000	0	0
GNRH1	0.005	0.031	-10000	0	-0.29	6	6
Gi family/GTP	-0.059	0.12	-10000	0	-0.26	90	90
CDC42	0.011	0	-10000	0	-10000	0	0

×

S1P3 pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.007	0.085	-9999	-0.41	23	23
mol:S1P	-0.009	0.014	-9999	-10000	0	0
S1P1/S1P/Gi	-0.073	0.12	-9999	-0.24	156	156
GNAO1	-0.11	0.19	-9999	-0.42	143	143
S1P/S1P3/G12/G13	0.003	0.045	-9999	-0.22	19	19
AKT1	-0.063	0.16	-9999	-0.66	26	26
AKT3	-0.41	0.55	-9999	-1.1	204	204
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.007	0.085	-9999	-0.41	23	23
GNAI2	0.002	0.014	-9999	-10000	0	0
GNAI3	0.004	0.011	-9999	-10000	0	0
GNAI1	-0.002	0.052	-9999	-0.42	8	8
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.013	0.079	-9999	-0.42	19	19
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.13	0.2	-9999	-0.34	211	211
MAPK3	-0.12	0.19	-9999	-0.32	211	211
MAPK1	-0.12	0.19	-9999	-0.32	211	211
JAK2	-0.12	0.2	-9999	-0.33	211	211
CXCR4	-0.12	0.19	-9999	-0.32	211	211
FLT1	0.003	0.016	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	-0.12	0.19	-9999	-0.32	211	211
S1P/S1P3/Gi	-0.13	0.2	-9999	-0.34	211	211
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.12	0.18	-9999	-0.31	211	211
VEGFA	0.003	0.016	-9999	-10000	0	0
S1P/S1P2/Gi	-0.084	0.14	-9999	-0.27	148	148
VEGFR1 homodimer/VEGFA homodimer	0	0.031	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.02	0.1	-9999	-0.25	74	74
GNAQ	0.009	0.025	-9999	-0.41	2	2
GNAZ	-0.009	0.074	-9999	-0.41	17	17
G12/G13	0.016	0	-9999	-10000	0	0
GNA14	-0.031	0.13	-9999	-0.41	54	54
GNA15	0.007	0.038	-9999	-0.33	7	7
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
GNA11	0.002	0.062	-9999	-0.41	12	12
Rac1/GTP	-0.12	0.18	-9999	-0.31	211	211

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.009	0.031	-9999	-0.41	3	3
LAT2	-0.067	0.13	-9999	-0.23	169	169
AP1	-0.13	0.14	-9999	-0.35	108	108
mol:PIP3	-0.068	0.15	-9999	-0.26	171	171
IKBKB	-0.036	0.098	-9999	-0.22	54	54
AKT1	-0.032	0.1	-9999	-0.28	42	42
IKBKG	-0.036	0.098	-9999	-0.22	53	53
MS4A2	-0.12	0.19	-9999	-0.41	168	168
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
MAP3K1	-0.043	0.12	-9999	-0.31	39	39
mol:Ca2+	-0.051	0.12	-9999	-0.2	171	171
LYN	0.01	0.003	-9999	-10000	0	0
CBLB	-0.066	0.13	-9999	-0.23	169	169
SHC1	0.011	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.035	0.1	-9999	-0.21	131	131
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.01	0.018	-9999	-0.41	1	1
PLD2	-0.059	0.12	-9999	-0.25	93	93
PTPN13	-0.093	0.15	-9999	-0.38	69	69
PTPN11	0.009	0.005	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.03	0.11	-9999	-0.26	42	42
SYK	0.01	0.015	-9999	-0.33	1	1
GRB2	0.011	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.1	0.13	-9999	-0.26	171	171
LAT	-0.066	0.13	-9999	-0.23	169	169
PAK2	-0.053	0.13	-9999	-0.34	39	39
NFATC2	-0.082	0.16	-9999	-0.54	55	55
HRAS	-0.063	0.14	-9999	-0.24	168	168
GAB2	0.008	0.036	-9999	-0.41	4	4
PLA2G1B	0.028	0.015	-9999	-10000	0	0
Fc epsilon R1	-0.1	0.14	-9999	-0.25	225	225
Antigen/IgE/Fc epsilon R1	-0.092	0.12	-9999	-0.22	225	225
mol:GDP	-0.071	0.14	-9999	-0.26	169	169
JUN	0.006	0.047	-9999	-0.41	7	7
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
FOS	-0.12	0.19	-9999	-0.41	167	167
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.076	0.13	-9999	-0.25	169	169
CHUK	-0.036	0.098	-9999	-0.22	53	53
KLRG1	-0.057	0.11	-9999	-0.33	38	38
VAV1	-0.068	0.13	-9999	-0.23	169	169
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.066	0.13	-9999	-0.23	169	169
negative regulation of mast cell degranulation	-0.048	0.11	-9999	-0.3	38	38
BTK	-0.076	0.14	-9999	-0.26	169	169
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.078	0.15	-9999	-0.3	108	108
GAB2/PI3K/SHP2	-0.065	0.09	-9999	-0.31	42	42
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.066	0.13	-9999	-0.34	55	55
RAF1	0.019	0.018	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.083	0.11	-9999	-0.26	96	96
FCER1G	0.016	0.024	-9999	-0.33	2	2
FCER1A	-0.064	0.16	-9999	-0.42	93	93
Antigen/IgE/Fc epsilon R1/Fyn	-0.083	0.11	-9999	-0.25	107	107
MAPK3	0.027	0.015	-9999	-10000	0	0
MAPK1	0.027	0.015	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAPK8	-0.011	0.077	-9999	-0.55	7	7
DUSP1	-0.09	0.18	-9999	-0.41	130	130
NF-kappa-B/RelA	-0.037	0.046	-9999	-0.18	6	6
actin cytoskeleton reorganization	-0.077	0.14	-9999	-0.4	37	37
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.081	0.11	-9999	-0.34	42	42
FER	-0.066	0.13	-9999	-0.23	169	169
RELA	0.011	0	-9999	-10000	0	0
ITK	-0.032	0.061	-9999	-0.36	14	14
SOS1	0.011	0	-9999	-10000	0	0
PLCG1	-0.068	0.14	-9999	-0.26	169	169
cytokine secretion	-0.027	0.034	-9999	-10000	0	0
SPHK1	-0.067	0.13	-9999	-0.23	170	170
PTK2	-0.08	0.15	-9999	-0.41	37	37
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.1	0.14	-9999	-0.27	171	171
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.066	0.15	-9999	-0.36	53	53
MAP2K2	0.024	0.016	-9999	-10000	0	0
MAP2K1	0.024	0.016	-9999	-10000	0	0
MAP2K7	0.011	0	-9999	-10000	0	0
KLRG1/SHP2	-0.059	0.088	-9999	-0.29	38	38
MAP2K4	0.011	0.037	-9999	-0.84	1	1
Fc epsilon R1/FcgammaRIIB	-0.091	0.12	-9999	-0.22	224	224
mol:Choline	-0.058	0.12	-9999	-0.24	93	93
SHC/Grb2/SOS1	-0.07	0.11	-9999	-0.33	37	37
FYN	0.011	0	-9999	-10000	0	0
DOK1	0.011	0	-9999	-10000	0	0
PXN	-0.07	0.14	-9999	-0.38	37	37
HCLS1	-0.066	0.13	-9999	-0.23	170	170
PRKCB	-0.057	0.13	-9999	-0.31	56	56
FCGR2B	0.008	0.034	-9999	-0.39	4	4
IGHE	-0.001	0.004	-9999	-10000	0	0
KLRG1/SHIP	-0.049	0.11	-9999	-0.31	38	38
LCP2	0.01	0.015	-9999	-0.33	1	1
PLA2G4A	-0.077	0.14	-9999	-0.25	176	176
RASA1	0.007	0.04	-9999	-0.41	5	5
mol:Phosphatidic acid	-0.058	0.12	-9999	-0.24	93	93
IKK complex	-0.017	0.078	-9999	-0.16	53	53
WIPF1	0.009	0.025	-9999	-0.41	2	2

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.044	0.028	-9999	-10000	0	0
BUB1B	-0.06	0.05	-9999	-0.11	170	170
PLK1	-0.013	0.023	-9999	-10000	0	0
PLK1S1	-0.003	0.017	-9999	-0.26	1	1
KIF2A	-0.005	0.02	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.013	0.023	-9999	-10000	0	0
GOLGA2	0.011	0	-9999	-10000	0	0
Hec1/SPC24	-0.11	0.1	-9999	-0.18	342	342
WEE1	-0.008	0.022	-9999	-10000	0	0
cytokinesis	-0.078	0.042	-9999	-0.21	14	14
PP2A-alpha B56	0.037	0.005	-9999	-10000	0	0
AURKA	-0.004	0.014	-9999	-10000	0	0
PICH/PLK1	-0.079	0.11	-9999	-0.23	135	135
CENPE	-0.055	0.089	-9999	-0.19	161	161
RhoA/GTP	0.008	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.005	0.02	-9999	-10000	0	0
PPP2CA	0.011	0	-9999	-10000	0	0
FZR1	0.011	0	-9999	-10000	0	0
TPX2	-0.015	0.015	-9999	-10000	0	0
PAK1	0.01	0.001	-9999	-10000	0	0
SPC24	-0.2	0.17	-9999	-0.33	332	332
FBXW11	0.011	0	-9999	-10000	0	0
CLSPN	-0.013	0.018	-9999	-10000	0	0
GORASP1	0.011	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	-0.007	0.013	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
STAG2	0.011	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.012	0.007	-9999	-10000	0	0
spindle elongation	-0.013	0.023	-9999	-10000	0	0
ODF2	0.01	0.001	-9999	-10000	0	0
BUB1	0.023	0.013	-9999	-10000	0	0
TPT1	-0.003	0.013	-9999	-10000	0	0
CDC25C	-0.017	0.014	-9999	-10000	0	0
CDC25B	0.01	0.001	-9999	-10000	0	0
SGOL1	-0.044	0.028	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CCNB1/CDK1	-0.018	0.048	-9999	-10000	0	0
CDC14B	0.008	0.013	-9999	-0.3	1	1
CDC20	-0.29	0.11	-9999	-0.33	482	482
PLK1/PBIP1	-0.016	0.045	-9999	-0.18	34	34
mitosis	-0.004	0.007	-9999	-0.015	161	161
FBXO5	-0.005	0.02	-9999	-10000	0	0
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.014	0.089	-9999	-0.33	40	40
metaphase plate congression	-0.006	0.015	-9999	-10000	0	0
ERCC6L	-0.07	0.1	-9999	-0.26	72	72
NLP/gamma Tubulin	-0.005	0.012	-9999	-10000	0	0
microtubule cytoskeleton organization	-0.003	0.013	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0.01	0.018	-9999	-0.41	1	1
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.15	0.069	-9999	-0.17	491	491
GRASP65/GM130/RAB1/GTP/PLK1	0.008	0.018	-9999	-10000	0	0
RAB1A	0.011	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.006	0.022	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.018	-9999	-0.19	1	1
microtubule-based process	-0.16	0.06	-9999	-0.18	491	491
Golgi organization	-0.013	0.023	-9999	-10000	0	0
Cohesin/SA2	-0.013	0.014	-9999	-10000	0	0
PPP1CB/MYPT1	0.015	0.013	-9999	-0.28	1	1
KIF20A	-0.3	0.1	-9999	-0.33	491	491
APC/C/CDC20	-0.15	0.065	-9999	-0.18	482	482
PPP2R1A	0.011	0	-9999	-10000	0	0
chromosome segregation	-0.019	0.043	-9999	-0.17	34	34
PRC1	-0.003	0.068	-9999	-0.33	23	23
ECT2	-0.016	0.05	-9999	-0.19	34	34
C13orf34	-0.005	0.02	-9999	-10000	0	0
NUDC	-0.006	0.015	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.059	0.05	-9999	-0.11	170	170
spindle assembly	-0.008	0.018	-9999	-10000	0	0
spindle stabilization	-0.003	0.017	-9999	-0.26	1	1
APC/C/HCDH1	0.014	0.011	-9999	-0.24	1	1
MKLP2/PLK1	-0.16	0.06	-9999	-0.18	491	491
CCNB1	-0.047	0.13	-9999	-0.33	94	94
PPP1CB	0.011	0.001	-9999	-10000	0	0
BTRC	0.011	0	-9999	-10000	0	0
ROCK2	-0.009	0.065	-9999	-0.4	14	14
TUBG1	-0.003	0.013	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.026	0.043	-9999	-10000	0	0
MLF1IP	-0.012	0.057	-9999	-0.23	34	34
INCENP	0.01	0.001	-9999	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.009	0.01	-9999	-0.22	1	1
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.011	0.022	-9999	-0.22	5	5
STXBP1	-0.018	0.11	-9999	-0.41	38	38
ACh/CHRNA1	-0.098	0.1	-9999	-0.23	196	196
RAB3GAP2/RIMS1/UNC13B	0.018	0.019	-9999	-0.17	5	5
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0.003	0.032	-9999	-0.33	5	5
mol:ACh	-0.043	0.056	-9999	-0.1	247	247
RAB3GAP2	0.011	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.062	0.076	-9999	-0.28	30	30
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.098	0.1	-9999	-0.23	196	196
UNC13B	0.011	0	-9999	-10000	0	0
CHRNA1	-0.11	0.16	-9999	-0.33	196	196
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.081	0.12	-9999	-0.3	119	119
SNAP25	-0.11	0.13	-9999	-0.25	247	247
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.081	0.17	-9999	-0.41	119	119
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.003	0.064	-9999	-0.23	39	39
STX1A/SNAP25 fragment 1/VAMP2	-0.062	0.076	-9999	-0.28	30	30

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.005	0.049	-9999	-0.24	22	22
ADCY5	-0.032	0.098	-9999	-0.24	102	102
ADCY6	0.015	0	-9999	-10000	0	0
ADCY7	0.015	0	-9999	-10000	0	0
ADCY1	0.003	0.053	-9999	-0.22	30	30
ADCY2	-0.12	0.12	-9999	-0.24	303	303
ADCY3	0.014	0.015	-9999	-0.24	2	2
ADCY8	0.008	0.018	-9999	-0.18	5	5
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	-0.018	0.085	-9999	-0.24	73	73
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.061	0.079	-9999	-0.17	131	131

×

Glypican 1 network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.11	0.12	-9999	-0.23	295	295
fibroblast growth factor receptor signaling pathway	-0.11	0.12	-9999	-0.23	295	295
LAMA1	-0.1	0.16	-9999	-0.33	183	183
PRNP	-0.048	0.15	-9999	-0.41	76	76
GPC1/SLIT2	-0.021	0.099	-9999	-0.28	69	69
SMAD2	0.022	0.033	-9999	-0.2	12	12
GPC1/PrPc/Cu2+	-0.02	0.086	-9999	-0.23	76	76
GPC1/Laminin alpha1	-0.062	0.11	-9999	-0.22	183	183
TDGF1	-0.019	0.1	-9999	-0.38	42	42
CRIPTO/GPC1	-0.005	0.073	-9999	-0.26	42	42
APP/GPC1	0.016	0	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	0.004	0.061	-9999	-0.2	42	42
FLT1	0.011	0	-9999	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.017	0.037	-9999	-0.23	12	12
SERPINC1	0.004	0.041	-9999	-0.33	8	8
FYN	0.004	0.061	-9999	-0.2	42	42
FGR	0	0.071	-9999	-0.22	51	51
positive regulation of MAPKKK cascade	0.015	0.073	-9999	-0.27	26	26
SLIT2	-0.043	0.14	-9999	-0.41	69	69
GPC1/NRG	0.005	0.057	-9999	-0.28	21	21
NRG1	-0.006	0.08	-9999	-0.41	21	21
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.022	0	-9999	-10000	0	0
LYN	0.004	0.061	-9999	-0.2	42	42
mol:Spermine	0.009	0	-9999	-10000	0	0
cell growth	-0.11	0.12	-9999	-0.23	295	295
BMP signaling pathway	-0.011	0	-9999	-10000	0	0
SRC	0.004	0.061	-9999	-0.2	42	42
TGFBR1	0.011	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.032	0.12	-9999	-0.39	55	55
GPC1	0.011	0	-9999	-10000	0	0
TGFBR1 (dimer)	0.011	0	-9999	-10000	0	0
VEGFA	0.011	0	-9999	-10000	0	0
BLK	-0.011	0.077	-9999	-0.2	79	79
HCK	0.002	0.064	-9999	-0.2	49	49
FGF2	-0.22	0.21	-9999	-0.41	295	295
FGFR1	0.01	0.018	-9999	-0.41	1	1
VEGFR1 homodimer	0.011	0	-9999	-10000	0	0
TGFBR2	0.002	0.062	-9999	-0.41	12	12
cell death	0.016	0	-9999	-10000	0	0
ATIII/GPC1	0.011	0.028	-9999	-0.22	8	8
PLA2G2A/GPC1	-0.014	0.085	-9999	-0.27	55	55
LCK	0.003	0.065	-9999	-0.21	46	46
neuron differentiation	0.005	0.056	-9999	-0.28	21	21
PrPc/Cu2+	-0.033	0.1	-9999	-0.29	76	76
APP	0.011	0	-9999	-10000	0	0
TGFBR2 (dimer)	0.002	0.062	-9999	-0.41	12	12

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.084	0.32	-9999	-0.96	62	62
MKNK1	0.011	0	-9999	-10000	0	0
MAPK14	-0.015	0.099	-9999	-0.27	69	69
ATF2/c-Jun	-0.004	0.11	-9999	-0.5	11	11
MAPK11	-0.017	0.1	-9999	-0.28	71	71
MITF	-0.043	0.17	-9999	-0.39	75	75
MAPKAPK5	-0.011	0.12	-9999	-0.32	71	71
KRT8	-0.028	0.13	-9999	-0.34	72	72
MAPKAPK3	0.011	0	-9999	-10000	0	0
MAPKAPK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.023	0.15	-9999	-0.4	69	69
CEBPB	-0.011	0.12	-9999	-0.32	71	71
SLC9A1	-0.011	0.12	-9999	-0.32	71	71
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.009	0.12	-9999	-0.31	72	72
p38alpha-beta/MNK1	-0.008	0.12	-9999	-0.31	69	69
JUN	-0.004	0.1	-9999	-0.49	11	11
PPARGC1A	-0.075	0.19	-9999	-0.4	88	88
USF1	-0.011	0.12	-9999	-0.32	71	71
RAB5/GDP/GDI1	-0.03	0.076	-9999	-0.23	69	69
NOS2	-0.021	0.16	-9999	-0.85	11	11
DDIT3	-0.011	0.12	-9999	-0.32	71	71
RAB5A	0.011	0	-9999	-10000	0	0
HSPB1	-0.002	0.099	-9999	-0.26	69	69
p38alpha-beta/HBP1	-0.008	0.12	-9999	-0.31	69	69
CREB1	-0.012	0.13	-9999	-0.34	71	71
RAB5/GDP	0.008	0	-9999	-10000	0	0
EIF4E	-0.003	0.1	-9999	-0.26	69	69
RPS6KA4	-0.011	0.12	-9999	-0.32	71	71
PLA2G4A	-0.015	0.12	-9999	-0.31	70	70
GDI1	-0.011	0.12	-9999	-0.32	69	69
TP53	-0.018	0.15	-9999	-0.39	69	69
RPS6KA5	-0.014	0.13	-9999	-0.32	76	76
ESR1	-0.047	0.18	-9999	-0.4	78	78
HBP1	0.011	0	-9999	-10000	0	0
MEF2C	-0.041	0.16	-9999	-0.39	73	73
MEF2A	-0.015	0.13	-9999	-0.33	75	75
EIF4EBP1	-0.012	0.13	-9999	-0.34	71	71
KRT19	-0.016	0.13	-9999	-0.32	76	76
ELK4	-0.011	0.12	-9999	-0.32	71	71
ATF6	-0.011	0.12	-9999	-0.32	71	71
ATF1	-0.012	0.13	-9999	-0.34	71	71
p38alpha-beta/MAPKAPK2	-0.008	0.12	-9999	-0.31	69	69
p38alpha-beta/MAPKAPK3	-0.008	0.12	-9999	-0.31	69	69

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.016	0.01	-9999	-0.22	1	1
VLDLR	0.009	0.025	-9999	-0.41	2	2
CRKL	0.011	0	-9999	-10000	0	0
LRPAP1	0.011	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
ITGA3	0.01	0.018	-9999	-0.41	1	1
RELN/VLDLR/Fyn	-0.07	0.12	-9999	-0.23	201	201
MAPK8IP1/MKK7/MAP3K11/JNK1	0.03	0.025	-9999	-0.18	7	7
AKT1	-0.052	0.1	-9999	-0.18	199	199
MAP2K7	0.011	0	-9999	-10000	0	0
RAPGEF1	0.011	0	-9999	-10000	0	0
DAB1	-0.001	0.052	-9999	-0.33	13	13
RELN/LRP8/DAB1	-0.07	0.11	-9999	-0.2	214	214
LRPAP1/LRP8	0.014	0.022	-9999	-0.22	5	5
RELN/LRP8/DAB1/Fyn	-0.059	0.1	-9999	-0.19	195	195
DAB1/alpha3/beta1 Integrin	-0.062	0.08	-9999	-0.33	5	5
long-term memory	-0.13	0.15	-9999	-0.36	107	107
DAB1/LIS1	-0.066	0.083	-9999	-0.31	5	5
DAB1/CRLK/C3G	-0.062	0.078	-9999	-0.3	5	5
PIK3CA	0.01	0.018	-9999	-0.41	1	1
DAB1/NCK2	-0.066	0.084	-9999	-0.31	5	5
ARHGEF2	0.011	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.15	0.2	-9999	-0.41	212	212
CDK5R1	0.01	0.015	-9999	-0.33	1	1
RELN	-0.14	0.2	-9999	-0.41	200	200
PIK3R1	0.007	0.04	-9999	-0.41	5	5
RELN/LRP8/Fyn	-0.071	0.12	-9999	-0.23	202	202
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.13	0.15	-9999	-0.35	124	124
MAPK8	0.006	0.044	-9999	-0.41	6	6
RELN/VLDLR/DAB1	-0.069	0.11	-9999	-0.2	213	213
ITGB1	0.011	0	-9999	-10000	0	0
MAP1B	-0.068	0.11	-9999	-0.2	205	205
RELN/LRP8	-0.071	0.12	-9999	-0.23	202	202
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.062	0.11	-9999	-0.21	55	55
PI3K	0.013	0.031	-9999	-0.28	6	6
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.016	0.013	-9999	-0.28	1	1
RAP1A	-0.032	0.092	-9999	-0.28	5	5
PAFAH1B1	0.011	0	-9999	-10000	0	0
MAPK8IP1	0.01	0.023	-9999	-0.37	2	2
CRLK/C3G	0.016	0	-9999	-10000	0	0
GRIN2B	-0.007	0.065	-9999	-0.33	21	21
NCK2	0.011	0	-9999	-10000	0	0
neuron differentiation	-0.031	0.083	-9999	-0.28	2	2
neuron adhesion	-0.021	0.091	-9999	-0.29	5	5
LRP8	0.008	0.032	-9999	-0.33	5	5
GSK3B	-0.044	0.096	-9999	-0.36	1	1
RELN/VLDLR/DAB1/Fyn	-0.058	0.1	-9999	-0.19	195	195
MAP3K11	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.062	0.11	-9999	-0.2	200	200
CDK5	0.011	0	-9999	-10000	0	0
MAPT	0.002	0.076	-9999	-0.37	20	20
neuron migration	-0.051	0.13	-9999	-0.32	4	4
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.031	0.083	-9999	-0.28	2	2
RELN/VLDLR	-0.057	0.11	-9999	-0.2	195	195

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.012	0.043	-9999	-10000	0	0
BIRC5	-0.25	0.14	-9999	-0.33	423	423
NFKBIA	-0.013	0.042	-9999	-10000	0	0
CPEB1	-0.17	0.21	-9999	-0.41	236	236
AKT1	-0.013	0.042	-9999	-10000	0	0
NDEL1	0.011	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.011	0.038	-9999	-10000	0	0
NDEL1/TACC3	-0.04	0.09	-9999	-0.22	86	86
GADD45A	0.011	0	-9999	-10000	0	0
GSK3B	0.007	0.001	-9999	-10000	0	0
PAK1/Aurora A	-0.012	0.043	-9999	-10000	0	0
MDM2	0.011	0	-9999	-10000	0	0
JUB	0.011	0	-9999	-10000	0	0
TPX2	-0.17	0.092	-9999	-0.22	441	441
TP53	0	0.029	-9999	-0.28	1	1
DLG7	-0.021	0.042	-9999	-10000	0	0
AURKAIP1	0.011	0	-9999	-10000	0	0
ARHGEF7	0.011	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.043	0.096	-9999	-0.23	86	86
G2/M transition of mitotic cell cycle	-0.011	0.038	-9999	-10000	0	0
AURKA	-0.024	0.053	-9999	-10000	0	0
AURKB	-0.014	0.013	-9999	-10000	0	0
CDC25B	-0.005	0.032	-9999	-10000	0	0
G2/M transition checkpoint	-0.011	0.038	-9999	-10000	0	0
mRNA polyadenylation	-0.11	0.12	-9999	-0.23	236	236
Aurora A/CPEB	-0.11	0.12	-9999	-0.24	236	236
Aurora A/TACC1/TRAP/chTOG	-0.034	0.092	-9999	-0.21	98	98
BRCA1	0.011	0	-9999	-10000	0	0
centrosome duplication	-0.012	0.042	-9999	-10000	0	0
regulation of centrosome cycle	-0.04	0.089	-9999	-0.22	86	86
spindle assembly	-0.034	0.09	-9999	-0.21	98	98
TDRD7	0.011	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.12	0.086	-9999	-0.21	167	167
CENPA	-0.003	0.016	-9999	-10000	0	0
Aurora A/PP2A	-0.012	0.043	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.002	0.028	-9999	-10000	0	0
negative regulation of DNA binding	0	0.029	-9999	-0.28	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.016	0	-9999	-10000	0	0
RASA1	0.007	0.04	-9999	-0.41	5	5
Ajuba/Aurora A	-0.011	0.038	-9999	-10000	0	0
mitotic prometaphase	-0.02	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.024	0.053	-9999	-10000	0	0
TACC1	-0.065	0.16	-9999	-0.41	98	98
TACC3	-0.068	0.14	-9999	-0.33	126	126
Aurora A/Antizyme1	-0.003	0.038	-9999	-10000	0	0
Aurora A/RasGAP	-0.015	0.048	-9999	-0.24	5	5
OAZ1	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.007	0.001	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.022	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.17	0.092	-9999	-0.22	441	441
PPP2R5D	0.011	0	-9999	-10000	0	0
Aurora A/TPX2	-0.14	0.088	-9999	-0.23	162	162
PAK1	0.011	0	-9999	-10000	0	0
CKAP5	0.011	0	-9999	-10000	0	0

×

IGF1 pathway

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
NCK2	0.011	0	-10000	0	-10000	0	0
PTK2	0.011	0	-10000	0	-10000	0	0
CRKL	-0.041	0.12	-10000	0	-0.25	111	111
GRB2/SOS1/SHC	0.022	0	-10000	0	-10000	0	0
HRAS	0.011	0	-10000	0	-10000	0	0
IRS1/Crk	-0.041	0.12	-10000	0	-0.25	111	111
IGF-1R heterotetramer/IGF1/PTP1B	-0.034	0.11	-10000	0	-0.25	111	111
AKT1	-0.021	0.11	-10000	0	-0.32	38	38
BAD	-0.014	0.1	-10000	0	-0.3	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.041	0.12	-10000	0	-0.25	111	111
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.041	0.12	-10000	0	-0.26	111	111
RAF1	-0.009	0.099	-10000	0	-0.28	38	38
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.031	0.12	-10000	0	-0.24	111	111
YWHAZ	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.051	0.13	-10000	0	-0.28	111	111
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
RPS6KB1	-0.021	0.11	-10000	0	-0.32	38	38
GNB2L1	0.011	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.009	0.087	-10000	0	-0.25	38	38
PXN	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
HRAS/GTP	-0.045	0.091	-10000	0	-0.32	37	37
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.012	0.091	-10000	0	-0.24	37	37
IGF-1R heterotetramer	-0.019	0.093	-10000	0	-0.46	21	21
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.04	0.12	-10000	0	-0.26	111	111
Crk/p130 Cas/Paxillin	-0.025	0.11	-10000	0	-0.34	37	37
IGF1R	-0.019	0.093	-10000	0	-0.47	21	21
IGF1	-0.075	0.17	-10000	0	-0.44	101	101
IRS2/Crk	-0.058	0.14	-10000	0	-0.25	161	161
PI3K	-0.034	0.12	-10000	0	-0.24	114	114
apoptosis	0.006	0.091	0.26	38	-10000	0	38
HRAS/GDP	0.008	0	-10000	0	-10000	0	0
PRKCD	-0.046	0.15	-10000	0	-0.34	111	111
RAF1/14-3-3 E	-0.001	0.089	-10000	0	-0.28	13	13
BAD/14-3-3	-0.007	0.096	-10000	0	-0.28	38	38
PRKCZ	-0.021	0.11	-10000	0	-0.32	38	38
Crk/p130 Cas/Paxillin/FAK1	-0.038	0.077	-10000	0	-0.27	38	38
PTPN1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.054	0.16	-10000	0	-0.36	111	111
BCAR1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.022	0.099	-10000	0	-0.21	112	112
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.011	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.04	0.12	-10000	0	-0.25	111	111
GRB10	0.01	0.018	-10000	0	-0.41	1	1
PTPN11	-0.041	0.12	-10000	0	-0.25	111	111
IRS1	-0.045	0.13	-10000	0	-0.28	111	111
IRS2	-0.068	0.14	-10000	0	-0.27	161	161
IGF-1R heterotetramer/IGF1	-0.059	0.15	-10000	0	-0.34	111	111
GRB2	0.011	0	-10000	0	-10000	0	0
PDPK1	-0.027	0.11	-10000	0	-0.34	38	38
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKD1	-0.06	0.17	-10000	0	-0.36	115	115
SHC1	0.011	0	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.054	0.089	-10000	0	-0.24	38	38
NT3 (dimer)/TRKC	-0.14	0.17	-10000	0	-0.3	269	269
NT3 (dimer)/TRKB	-0.11	0.16	-10000	0	-0.28	237	237
SHC/Grb2/SOS1/GAB1/PI3K	0.026	0.03	-10000	0	-10000	0	0
RAPGEF1	0.011	0	-10000	0	-10000	0	0
BDNF	-0.044	0.12	-10000	0	-0.33	88	88
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
DYNLT1	0.011	0	-10000	0	-10000	0	0
NTRK1	0.001	0.058	-10000	0	-0.37	13	13
NTRK2	-0.041	0.14	-10000	0	-0.4	69	69
NTRK3	-0.19	0.21	-10000	0	-0.41	257	257
NT-4/5 (dimer)/TRKB	-0.1	0.15	-10000	0	-0.26	238	238
neuron apoptosis	0.14	0.19	0.4	149	-10000	0	149
SHC 2-3/Grb2	-0.15	0.21	-10000	0	-0.43	149	149
SHC1	0.011	0	-10000	0	-10000	0	0
SHC2	-0.18	0.24	0.17	1	-0.51	153	154
SHC3	-0.12	0.16	0.17	1	-0.38	110	111
STAT3 (dimer)	0.017	0.01	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.084	0.14	-10000	0	-0.25	214	214
RIN/GDP	-0.044	0.08	-10000	0	-0.2	26	26
GIPC1	0.011	0	-10000	0	-10000	0	0
KRAS	0.01	0.015	-10000	0	-0.33	1	1
DNAJA3	-0.13	0.16	0.2	2	-0.32	186	188
RIN/GTP	0.002	0.003	-10000	0	-10000	0	0
CCND1	0.023	0.018	-10000	0	-10000	0	0
MAGED1	0.009	0.025	-10000	0	-0.41	2	2
PTPN11	0.011	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.006	0.07	-10000	0	-0.33	24	24
SHC/GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
GRB2	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.042	0.11	-10000	0	-0.24	131	131
TRKA/NEDD4-2	0.009	0.042	-10000	0	-0.25	14	14
ELMO1	0.008	0.036	-10000	0	-0.41	4	4
RhoG/GTP/ELMO1/DOCK1	0.01	0.038	-10000	0	-0.26	10	10
NGF	-0.078	0.17	-10000	0	-0.41	115	115
HRAS	0.011	0	-10000	0	-10000	0	0
DOCK1	0.006	0.047	-10000	0	-0.41	7	7
GAB2	0.008	0.036	-10000	0	-0.41	4	4
RIT2	0.002	0.004	-10000	0	-10000	0	0
RIT1	0.011	0	-10000	0	-10000	0	0
FRS2	0.011	0	-10000	0	-10000	0	0
DNM1	0.006	0.044	-10000	0	-0.41	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.12	0.16	0.19	2	-0.31	186	188
mol:GDP	-0.064	0.11	-10000	0	-0.26	45	45
NGF (dimer)	-0.078	0.17	-10000	0	-0.41	115	115
RhoG/GDP	0.006	0.025	-10000	0	-0.29	4	4
RIT1/GDP	-0.04	0.08	-10000	0	-0.2	22	22
TIAM1	0	0.067	-10000	0	-0.41	14	14
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
BDNF (dimer)/TRKB	-0.04	0.1	-10000	0	-0.24	61	61
KIDINS220/CRKL/C3G	0.016	0	-10000	0	-10000	0	0
SHC/RasGAP	0.014	0.028	-10000	0	-0.28	5	5
FRS2 family/SHP2	0.022	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.027	0.019	-10000	0	-0.2	4	4
RIT1/GTP	0.008	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.018	0.1	-10000	0	-0.4	38	38
RAP1/GDP	-0.048	0.053	-10000	0	-0.17	18	18
KIDINS220/CRKL	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.044	0.12	-10000	0	-0.33	88	88
ubiquitin-dependent protein catabolic process	-0.037	0.11	-10000	0	-0.23	122	122
Schwann cell development	-0.037	0.03	-10000	0	-10000	0	0
EHD4	0.011	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.031	0.017	-10000	0	-10000	0	0
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.12	-10000	0	-0.34	105	105
ABL1	0.009	0.025	-10000	0	-0.41	2	2
SH2B family/GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
Rap1/GTP	0.014	0.046	-10000	0	-10000	0	0
STAT3	0.017	0.01	-10000	0	-10000	0	0
axon guidance	-0.12	0.12	-10000	0	-0.32	105	105
MAPK3	-0.032	0.1	-10000	0	-0.21	130	130
MAPK1	-0.032	0.1	-10000	0	-0.21	130	130
CDC42/GDP	-0.04	0.08	-10000	0	-0.19	26	26
NTF3	-0.018	0.1	-10000	0	-0.4	38	38
NTF4	-0.006	0.07	-10000	0	-0.33	24	24
NGF (dimer)/TRKA/FAIM	-0.037	0.11	-10000	0	-0.23	123	123
PI3K	0.013	0.031	-10000	0	-0.28	6	6
FRS3	0.011	0	-10000	0	-10000	0	0
FAIM	0.01	0.018	-10000	0	-0.41	1	1
GAB1	0.008	0.036	-10000	0	-0.41	4	4
RASGRF1	-0.15	0.17	0.2	2	-0.3	268	270
SOS1	0.011	0	-10000	0	-10000	0	0
MCF2L	-0.11	0.14	-10000	0	-0.25	270	270
RGS19	0.011	0	-10000	0	-10000	0	0
CDC42	0.011	0	-10000	0	-10000	0	0
RAS family/GTP	-0.017	0.07	-10000	0	-10000	0	0
Rac1/GDP	-0.04	0.08	-10000	0	-0.2	22	22
NGF (dimer)/TRKA/GRIT	-0.043	0.11	-10000	0	-0.24	126	126
neuron projection morphogenesis	-0.11	0.17	-10000	0	-0.43	69	69
NGF (dimer)/TRKA/NEDD4-2	-0.036	0.11	-10000	0	-0.23	122	122
MAP2K1	0.029	0.018	-10000	0	-10000	0	0
NGFR	-0.13	0.2	-10000	0	-0.41	185	185
NGF (dimer)/TRKA/GIPC/GAIP	-0.023	0.096	-10000	0	-0.33	4	4
RAS family/GTP/PI3K	0.023	0.023	-10000	0	-0.2	6	6
FRS2 family/SHP2/GRB2/SOS1	0.033	0	-10000	0	-10000	0	0
NRAS	0.011	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.023	-10000	0	-0.37	2	2
MAPKKK cascade	-0.15	0.25	-10000	0	-0.6	122	122
RASA1	0.007	0.04	-10000	0	-0.41	5	5
TRKA/c-Abl	0.009	0.044	-10000	0	-0.25	15	15
SQSTM1	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.028	0.093	-10000	0	-0.21	61	61
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.018	0.091	-10000	0	-0.21	12	12
MATK	0	0.066	-10000	0	-0.4	14	14
NEDD4L	0.01	0.018	-10000	0	-0.41	1	1
RAS family/GDP	-0.045	0.05	-10000	0	-0.17	15	15
NGF (dimer)/TRKA	-0.14	0.17	0.21	2	-0.31	238	240
Rac1/GTP	-0.11	0.11	-10000	0	-0.26	171	171
FRS2 family/SHP2/CRK family	0.033	0	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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
CDKN2B	0.001	0.048	-10000	0	-0.35	9	9
CDKN2C	0.021	0.055	-10000	0	-0.38	9	9
CDKN2A	-0.13	0.17	-10000	0	-0.34	228	228
CCND2	0.005	0.049	0.16	10	-0.1	43	53
RB1	-0.006	0.048	0.13	5	-0.16	12	17
CDK4	0.024	0.037	0.17	12	-10000	0	12
CDK6	0.016	0.045	0.17	12	-0.18	11	23
G1/S progression	0.006	0.048	0.16	12	-0.13	5	17

×

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

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
MAP4K1	-0.029	0.14	-10000	0	-0.41	52	52
CRKL	-0.033	0.15	-10000	0	-0.44	49	49
HRAS	-0.012	0.13	-10000	0	-0.38	46	46
mol:PIP3	-0.039	0.14	-10000	0	-0.4	54	54
SPRED1	0.011	0	-10000	0	-10000	0	0
SPRED2	0.01	0.018	-10000	0	-0.41	1	1
GAB1	-0.041	0.16	-10000	0	-0.37	79	79
FOXO3	-0.024	0.14	-10000	0	-0.39	49	49
AKT1	-0.033	0.15	-10000	0	-0.43	49	49
BAD	-0.024	0.14	-10000	0	-0.39	49	49
megakaryocyte differentiation	-0.042	0.16	-10000	0	-0.36	84	84
GSK3B	-0.024	0.14	-10000	0	-0.39	49	49
RAF1	-0.002	0.11	-10000	0	-0.3	46	46
SHC1	0.011	0	-10000	0	-10000	0	0
STAT3	-0.039	0.16	-10000	0	-0.37	79	79
STAT1	-0.099	0.34	-10000	0	-0.84	82	82
HRAS/SPRED1	-0.004	0.11	-10000	0	-0.3	46	46
cell proliferation	-0.04	0.16	-10000	0	-0.36	82	82
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
TEC	0.01	0.015	-10000	0	-0.33	1	1
RPS6KB1	-0.04	0.16	-10000	0	-0.44	55	55
HRAS/SPRED2	-0.004	0.11	-10000	0	-0.31	46	46
LYN/TEC/p62DOK	-0.027	0.15	-10000	0	-0.42	50	50
MAPK3	0.01	0.086	-10000	0	-0.21	46	46
STAP1	-0.042	0.16	-10000	0	-0.36	82	82
GRAP2	-0.002	0.073	-10000	0	-0.41	17	17
JAK2	-0.086	0.3	-10000	0	-0.72	82	82
STAT1 (dimer)	-0.096	0.33	-10000	0	-0.82	82	82
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.028	0.15	-10000	0	-0.42	52	52
actin filament polymerization	-0.038	0.15	-10000	0	-0.36	80	80
LYN	0.011	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.053	0.21	-10000	0	-0.51	82	82
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
CBL/CRKL/GRB2	-0.019	0.14	-10000	0	-0.39	49	49
PI3K	-0.03	0.16	-10000	0	-0.45	51	51
PTEN	0.006	0.044	-10000	0	-0.41	6	6
SCF/KIT/EPO/EPOR	-0.1	0.37	-10000	0	-1.2	48	48
MAPK8	-0.041	0.16	-10000	0	-0.37	82	82
STAT3 (dimer)	-0.038	0.15	-10000	0	-0.36	80	80
positive regulation of transcription	0.012	0.073	-10000	0	-0.18	46	46
mol:GDP	-0.017	0.14	-10000	0	-0.39	47	47
PIK3C2B	-0.039	0.16	-10000	0	-0.37	80	80
CBL/CRKL	-0.025	0.14	-10000	0	-0.41	49	49
FER	-0.039	0.16	-10000	0	-0.36	82	82
SH2B3	-0.04	0.16	-10000	0	-0.36	82	82
PDPK1	-0.031	0.13	-10000	0	-0.38	51	51
SNAI2	-0.064	0.18	-10000	0	-0.42	90	90
positive regulation of cell proliferation	-0.069	0.26	-10000	0	-0.62	82	82
KITLG	-0.029	0.13	-10000	0	-0.43	50	50
cell motility	-0.069	0.26	-10000	0	-0.62	82	82
PTPN6	0.011	0.017	-10000	0	-0.33	1	1
EPOR	-0.01	0.12	-10000	0	-0.62	3	3
STAT5A (dimer)	-0.055	0.22	-10000	0	-0.52	82	82
SOCS1	0.01	0.018	-10000	0	-0.41	1	1
cell migration	0.043	0.16	0.36	81	-10000	0	81
SOS1	0.011	0	-10000	0	-10000	0	0
EPO	-0.005	0.074	-10000	0	-0.41	17	17
VAV1	0.007	0.037	-10000	0	-0.34	6	6
GRB10	-0.04	0.16	-10000	0	-0.36	83	83
PTPN11	0.012	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.047	0.16	-10000	0	-0.38	83	83
GO:0007205	0.001	0.008	-10000	0	-10000	0	0
MAP2K1	0.007	0.093	-10000	0	-0.24	46	46
CBL	0.011	0	-10000	0	-10000	0	0
KIT	-0.079	0.34	-10000	0	-1.2	41	41
MAP2K2	0.007	0.093	-10000	0	-0.24	46	46
SHC/Grb2/SOS1	-0.026	0.15	-10000	0	-0.42	49	49
STAT5A	-0.058	0.22	-10000	0	-0.53	82	82
GRB2	0.011	0	-10000	0	-10000	0	0
response to radiation	-0.063	0.18	-10000	0	-0.41	90	90
SHC/GRAP2	0.007	0.052	-10000	0	-0.28	17	17
PTPRO	-0.043	0.16	-10000	0	-0.37	84	84
SH2B2	-0.039	0.16	-10000	0	-0.37	80	80
DOK1	0.011	0	-10000	0	-10000	0	0
MATK	-0.044	0.16	-10000	0	-0.37	81	81
CREBBP	0.016	0.045	-10000	0	-0.43	2	2
BCL2	-0.098	0.38	-10000	0	-1.2	51	51

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.035	0.13	-10000	0	-0.37	64	64
NFATC2	-0.023	0.18	-10000	0	-0.52	43	43
NFATC3	-0.015	0.083	-10000	0	-0.24	45	45
CD40LG	-0.17	0.33	-10000	0	-0.84	83	83
ITCH	0.026	0.038	-10000	0	-10000	0	0
CBLB	0.026	0.038	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.14	0.25	-10000	0	-0.79	41	41
JUNB	0.007	0.04	-10000	0	-0.41	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.01	0.037	-10000	0	-0.23	1	1
T cell anergy	0.015	0.059	-10000	0	-0.31	1	1
TLE4	-0.032	0.21	-10000	0	-0.64	52	52
Jun/NFAT1-c-4/p21SNFT	-0.093	0.33	-10000	0	-0.8	85	85
AP-1/NFAT1-c-4	-0.17	0.38	-10000	0	-0.96	81	81
IKZF1	0.002	0.13	-10000	0	-0.43	23	23
T-helper 2 cell differentiation	-0.082	0.23	-10000	0	-0.73	38	38
AP-1/NFAT1	-0.082	0.18	-10000	0	-0.4	80	80
CALM1	0.015	0.026	-10000	0	-10000	0	0
EGR2	-0.11	0.4	-10000	0	-0.93	85	85
EGR3	-0.14	0.46	-10000	0	-1.2	79	79
NFAT1/FOXP3	-0.044	0.16	-10000	0	-0.39	52	52
EGR1	-0.045	0.14	-10000	0	-0.41	71	71
JUN	0	0.049	-10000	0	-0.41	7	7
EGR4	-0.003	0.057	-10000	0	-0.34	15	15
mol:Ca2+	0.003	0.028	-10000	0	-10000	0	0
GBP3	-0.001	0.14	-10000	0	-0.5	22	22
FOSL1	-0.015	0.091	-10000	0	-0.33	42	42
NFAT1-c-4/MAF/IRF4	-0.12	0.35	-10000	0	-0.85	86	86
DGKA	0.004	0.12	-10000	0	-0.42	20	20
CREM	0.011	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.1	0.34	-10000	0	-0.83	85	85
CTLA4	-0.042	0.16	-10000	0	-0.43	44	44
NFAT1-c-4 (dimer)/EGR1	-0.12	0.36	-10000	0	-0.87	85	85
NFAT1-c-4 (dimer)/EGR4	-0.099	0.34	-10000	0	-0.82	85	85
FOS	-0.12	0.19	-10000	0	-0.41	167	167
IFNG	-0.076	0.19	-10000	0	-0.66	28	28
T cell activation	-0.083	0.21	-10000	0	-0.62	44	44
MAF	-0.066	0.16	-10000	0	-0.41	100	100
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.079	0.3	0.72	85	-10000	0	85
TNF	-0.13	0.33	-10000	0	-0.79	87	87
FASLG	-0.16	0.47	-10000	0	-1.2	85	85
TBX21	0.002	0.061	-10000	0	-0.4	12	12
BATF3	0.01	0.015	-10000	0	-0.33	1	1
PRKCQ	-0.024	0.12	-10000	0	-0.41	48	48
PTPN1	0.004	0.12	-10000	0	-0.41	22	22
NFAT1-c-4/ICER1	-0.094	0.33	-10000	0	-0.81	85	85
GATA3	-0.002	0.069	-10000	0	-0.35	20	20
T-helper 1 cell differentiation	-0.064	0.2	-10000	0	-0.64	29	29
IL2RA	-0.13	0.25	-10000	0	-0.68	60	60
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.004	0.12	-10000	0	-0.44	17	17
E2F1	-0.047	0.13	-10000	0	-0.32	102	102
PPARG	-0.012	0.096	-10000	0	-0.41	30	30
SLC3A2	0.004	0.12	-10000	0	-0.44	17	17
IRF4	-0.002	0.071	-10000	0	-0.37	19	19
PTGS2	-0.19	0.35	-10000	0	-0.83	95	95
CSF2	-0.17	0.33	-10000	0	-0.83	82	82
JunB/Fra1/NFAT1-c-4	-0.094	0.32	-10000	0	-0.78	85	85
IL4	-0.086	0.24	-10000	0	-0.77	37	37
IL5	-0.17	0.32	-10000	0	-0.84	80	80
IL2	-0.084	0.21	-10000	0	-0.63	44	44
IL3	-0.037	0.048	-10000	0	-10000	0	0
RNF128	0.012	0.08	-10000	0	-0.48	1	1
NFATC1	-0.079	0.3	-10000	0	-0.72	85	85
CDK4	0.041	0.18	0.58	17	-10000	0	17
PTPRK	0.003	0.13	-10000	0	-0.46	15	15
IL8	-0.2	0.34	-10000	0	-0.83	88	88
POU2F1	0.011	0	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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
TGM2	-0.033	0.13	-10000	0	-0.41	56	56
GNB1/GNG2	-0.04	0.072	-10000	0	-0.19	95	95
AKT1	-0.016	0.097	-10000	0	-0.2	93	93
EGF	-0.006	0.073	-10000	0	-0.34	25	25
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.018	0.053	-10000	0	-0.3	1	1
mol:Ca2+	-0.046	0.14	-10000	0	-0.3	118	118
LYN	0.021	0.047	-10000	0	-10000	0	0
RhoA/GTP	-0.028	0.049	-10000	0	-0.13	96	96
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.045	0.16	-10000	0	-0.34	98	98
GNG2	0.003	0.056	-10000	0	-0.4	10	10
ARRB2	0.011	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.005	0.071	-10000	0	-0.33	15	15
G beta5/gamma2	-0.053	0.096	-10000	0	-0.25	95	95
PRKCH	-0.053	0.16	-10000	0	-0.36	102	102
DNM1	0.006	0.044	-10000	0	-0.41	6	6
TXA2/TP beta/beta Arrestin3	-0.004	0.021	-10000	0	-0.21	1	1
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.026	0.12	-10000	0	-0.41	47	47
G12 family/GTP	-0.07	0.12	-10000	0	-0.3	108	108
ADRBK1	0.011	0	-10000	0	-10000	0	0
ADRBK2	0.01	0.018	-10000	0	-0.41	1	1
RhoA/GTP/ROCK1	0.012	0.006	-10000	0	-10000	0	0
mol:GDP	0.022	0.093	0.24	39	-10000	0	39
mol:NADP	0.009	0.023	-10000	0	-0.37	2	2
RAB11A	0.011	0	-10000	0	-10000	0	0
PRKG1	-0.18	0.21	-10000	0	-0.41	241	241
mol:IP3	-0.061	0.18	-10000	0	-0.38	118	118
cell morphogenesis	0.012	0.006	-10000	0	-10000	0	0
PLCB2	-0.09	0.23	-10000	0	-0.52	110	110
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.007	0.056	-10000	0	-0.25	2	2
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.019	0.049	-10000	0	-0.26	1	1
RHOA	0.011	0	-10000	0	-10000	0	0
PTGIR	0.01	0.018	-10000	0	-0.41	1	1
PRKCB1	-0.058	0.17	-10000	0	-0.38	109	109
GNAQ	0.009	0.025	-10000	0	-0.41	2	2
mol:L-citrulline	0.009	0.023	-10000	0	-0.37	2	2
TXA2/TXA2-R family	-0.084	0.23	-10000	0	-0.54	100	100
LCK	0.02	0.048	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.014	0.045	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.018	0.028	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.014	0.044	-10000	0	-10000	0	0
MAPK14	-0.022	0.11	-10000	0	-0.23	96	96
TGM2/GTP	-0.078	0.21	-10000	0	-0.45	122	122
MAPK11	-0.023	0.11	-10000	0	-0.23	98	98
ARHGEF1	-0.018	0.085	-10000	0	-0.18	98	98
GNAI2	0.011	0	-10000	0	-10000	0	0
JNK cascade	-0.056	0.17	-10000	0	-0.38	108	108
RAB11/GDP	0.011	0.001	-10000	0	-10000	0	0
ICAM1	-0.034	0.13	-10000	0	-0.28	96	96
cAMP biosynthetic process	-0.062	0.17	-10000	0	-0.36	122	122
Gq family/GTP/EBP50	-0.001	0.068	-10000	0	-0.18	64	64
actin cytoskeleton reorganization	0.012	0.006	-10000	0	-10000	0	0
SRC	0.021	0.047	-10000	0	-10000	0	0
GNB5	0.011	0	-10000	0	-10000	0	0
GNB1	0.011	0	-10000	0	-10000	0	0
EGF/EGFR	0.031	0.047	-10000	0	-0.21	3	3
VCAM1	-0.043	0.15	-10000	0	-0.33	96	96
TP beta/Gq family/GDP/G beta5/gamma2	0.005	0.071	-10000	0	-0.33	15	15
platelet activation	-0.031	0.14	-10000	0	-0.3	103	103
PGI2/IP	0.008	0.013	-10000	0	-0.29	1	1
PRKACA	-0.003	0.063	-10000	0	-0.21	48	48
Gq family/GDP/G beta5/gamma2	0.003	0.07	-10000	0	-0.25	26	26
TXA2/TP beta/beta Arrestin2	-0.006	0.046	-10000	0	-0.44	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.003	0.059	-10000	0	-0.19	48	48
mol:DAG	-0.068	0.19	-10000	0	-0.42	108	108
EGFR	0	0.066	-10000	0	-0.4	14	14
TXA2/TP alpha	-0.088	0.23	-10000	0	-0.49	122	122
Gq family/GTP	-0.023	0.07	-10000	0	-0.2	64	64
YES1	0.021	0.047	-10000	0	-10000	0	0
GNAI2/GTP	-0.013	0.041	-10000	0	-10000	0	0
PGD2/DP	-0.018	0.083	-10000	0	-0.29	47	47
SLC9A3R1	0.008	0.029	-10000	0	-0.33	4	4
FYN	0.021	0.047	-10000	0	-10000	0	0
mol:NO	0.009	0.023	-10000	0	-0.37	2	2
GNA15	0.007	0.038	-10000	0	-0.33	7	7
PGK/cGMP	-0.097	0.12	-10000	0	-0.24	242	242
RhoA/GDP	0.011	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.002	0.09	-10000	0	-0.34	17	17
NOS3	0.009	0.023	-10000	0	-0.37	2	2
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.059	0.17	-10000	0	-0.37	106	106
PRKCB	-0.058	0.17	-10000	0	-0.38	102	102
PRKCE	-0.051	0.16	-10000	0	-0.36	100	100
PRKCD	-0.056	0.17	-10000	0	-0.38	99	99
PRKCG	-0.066	0.18	-10000	0	-0.4	103	103
muscle contraction	-0.076	0.22	-10000	0	-0.49	108	108
PRKCZ	-0.045	0.16	-10000	0	-0.35	98	98
ARR3	0.003	0.015	-10000	0	-0.33	1	1
TXA2/TP beta	0.01	0.055	-10000	0	-0.17	2	2
PRKCQ	-0.062	0.17	-10000	0	-0.38	103	103
MAPKKK cascade	-0.077	0.21	-10000	0	-0.47	109	109
SELE	-0.048	0.16	-10000	0	-0.36	96	96
TP beta/GNAI2/GDP/G beta/gamma	0.017	0.06	-10000	0	-0.33	2	2
ROCK1	0.011	0	-10000	0	-10000	0	0
GNA14	-0.031	0.13	-10000	0	-0.41	54	54
chemotaxis	-0.092	0.26	-10000	0	-0.61	96	96
GNA12	0.011	0	-10000	0	-10000	0	0
GNA13	0.011	0	-10000	0	-10000	0	0
GNA11	0.002	0.062	-10000	0	-0.41	12	12
Rac1/GTP	0.006	0.004	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.062	0.15	-9999	-0.42	43	43
FZD6	0.01	0.018	-9999	-0.41	1	1
WNT6	-0.031	0.12	-9999	-0.38	58	58
WNT4	-0.088	0.18	-9999	-0.41	128	128
FZD3	0.011	0	-9999	-10000	0	0
WNT5A	-0.003	0.075	-9999	-0.41	18	18
WNT11	-0.03	0.12	-9999	-0.35	63	63

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.028	0.1	0.28	78	-10000	0	78
KIRREL	-0.039	0.14	-10000	0	-0.41	64	64
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.028	0.1	-10000	0	-0.28	78	78
PLCG1	0.011	0	-10000	0	-10000	0	0
ARRB2	0.011	0	-10000	0	-10000	0	0
WASL	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.011	0.076	-10000	0	-0.2	65	65
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.005	0.077	-10000	0	-0.21	64	64
FYN	-0.013	0.072	-10000	0	-0.2	65	65
mol:Ca2+	-0.015	0.074	-10000	0	-0.2	65	65
mol:DAG	-0.011	0.075	-10000	0	-0.2	65	65
NPHS2	-0.004	0.028	-10000	0	-0.33	3	3
mol:IP3	-0.011	0.075	-10000	0	-0.2	65	65
regulation of endocytosis	-0.006	0.068	-10000	0	-0.18	65	65
Nephrin/NEPH1/podocin/Cholesterol	-0.018	0.076	-10000	0	-0.2	74	74
establishment of cell polarity	-0.028	0.1	-10000	0	-0.28	78	78
Nephrin/NEPH1/podocin/NCK1-2	-0.003	0.072	-10000	0	-0.2	33	33
Nephrin/NEPH1/beta Arrestin2	-0.005	0.069	-10000	0	-0.18	65	65
NPHS1	-0.006	0.056	-10000	0	-0.33	15	15
Nephrin/NEPH1/podocin	-0.013	0.072	-10000	0	-0.2	65	65
TJP1	0.01	0.018	-10000	0	-0.41	1	1
NCK1	0.009	0.025	-10000	0	-0.41	2	2
NCK2	0.011	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.011	0.076	-10000	0	-0.2	65	65
CD2AP	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.011	0.076	-10000	0	-0.2	65	65
GRB2	0.011	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.027	0.097	-10000	0	-0.22	95	95
cytoskeleton organization	-0.001	0.08	-10000	0	-0.21	64	64
Nephrin/NEPH1	-0.017	0.071	-10000	0	-0.19	78	78
Nephrin/NEPH1/ZO-1	-0.014	0.083	-10000	0	-0.22	65	65

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.018	-9999	-0.41	1	1
CCL5	0.003	0.053	-9999	-0.37	11	11
SDCBP	0.011	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.07	0.07	-9999	-0.26	29	29
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.061	0.066	-9999	-0.24	29	29
Syndecan-1/Syntenin	-0.06	0.066	-9999	-0.24	29	29
MAPK3	-0.045	0.062	-9999	-0.25	15	15
HGF/MET	-0.049	0.12	-9999	-0.28	118	118
TGFB1/TGF beta receptor Type II	0.01	0.018	-9999	-0.41	1	1
BSG	0.011	0	-9999	-10000	0	0
keratinocyte migration	-0.06	0.066	-9999	-0.24	29	29
Syndecan-1/RANTES	-0.064	0.073	-9999	-0.26	37	37
Syndecan-1/CD147	-0.052	0.065	-9999	-0.26	15	15
Syndecan-1/Syntenin/PIP2	-0.058	0.063	-9999	-0.24	29	29
LAMA5	0.01	0.015	-9999	-0.33	1	1
positive regulation of cell-cell adhesion	-0.057	0.062	-9999	-0.23	29	29
MMP7	-0.058	0.14	-9999	-0.36	101	101
HGF	-0.076	0.17	-9999	-0.41	112	112
Syndecan-1/CASK	-0.067	0.066	-9999	-0.25	29	29
Syndecan-1/HGF/MET	-0.095	0.11	-9999	-0.28	115	115
regulation of cell adhesion	-0.038	0.06	-9999	-0.28	5	5
HPSE	0.002	0.06	-9999	-0.4	12	12
positive regulation of cell migration	-0.07	0.07	-9999	-0.26	29	29
SDC1	-0.071	0.07	-9999	-0.26	29	29
Syndecan-1/Collagen	-0.07	0.07	-9999	-0.26	29	29
PPIB	0.01	0.015	-9999	-0.33	1	1
MET	0.005	0.049	-9999	-0.37	9	9
PRKACA	0.011	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	222	222
MAPK1	-0.045	0.062	-9999	-0.25	15	15
homophilic cell adhesion	-0.07	0.069	-9999	-0.26	29	29
MMP1	-0.17	0.17	-9999	-0.33	292	292

×

Plasma membrane estrogen 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
GNB1/GNG2	-0.002	0.073	-10000	0	-0.19	71	71
ER alpha/Gai/GDP/Gbeta gamma	-0.087	0.19	-10000	0	-0.32	185	185
AKT1	-0.07	0.25	-10000	0	-0.74	63	63
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.075	0.25	-10000	0	-0.76	63	63
mol:Ca2+	-0.015	0.12	-10000	0	-0.34	57	57
IGF1R	-0.005	0.081	-10000	0	-0.41	21	21
E2/ER alpha (dimer)/Striatin	-0.014	0.08	-10000	0	-0.23	64	64
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	0.066	0.24	0.71	63	-10000	0	63
RhoA/GTP	-0.018	0.05	-10000	0	-0.3	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.087	0.14	-10000	0	-0.39	75	75
regulation of stress fiber formation	-0.017	0.058	0.26	3	-10000	0	3
E2/ERA-ERB (dimer)	-0.014	0.079	-10000	0	-0.23	63	63
KRAS	0.01	0.015	-10000	0	-0.33	1	1
G13/GTP	-0.011	0.071	-10000	0	-0.21	62	62
pseudopodium formation	0.017	0.058	-10000	0	-0.26	3	3
E2/ER alpha (dimer)/PELP1	-0.013	0.079	-10000	0	-0.23	62	62
GRB2	0.011	0	-10000	0	-10000	0	0
GNG2	0.003	0.056	-10000	0	-0.4	10	10
GNAO1	-0.1	0.18	-10000	0	-0.41	143	143
HRAS	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.056	0.18	-10000	0	-0.49	64	64
E2/ER beta (dimer)	0.008	0.01	-10000	0	-0.22	1	1
mol:GDP	-0.035	0.098	-10000	0	-0.31	62	62
mol:NADP	-0.056	0.18	-10000	0	-0.49	64	64
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
mol:IP3	-0.016	0.12	-10000	0	-0.36	57	57
IGF-1R heterotetramer	-0.005	0.081	-10000	0	-0.41	21	21
PLCB1	-0.022	0.13	-10000	0	-0.37	57	57
PLCB2	-0.021	0.13	-10000	0	-0.37	56	56
IGF1	-0.067	0.16	-10000	0	-0.41	101	101
mol:L-citrulline	-0.056	0.18	-10000	0	-0.49	64	64
RHOA	0.011	0	-10000	0	-10000	0	0
Gai/GDP	-0.15	0.29	-10000	0	-0.63	144	144
JNK cascade	0.008	0.01	-10000	0	-0.22	1	1
BCAR1	0.011	0	-10000	0	-10000	0	0
ESR2	0.01	0.015	-10000	0	-0.33	1	1
GNAQ	0.009	0.025	-10000	0	-0.41	2	2
ESR1	-0.037	0.13	-10000	0	-0.41	62	62
Gq family/GDP/Gbeta gamma	-0.002	0.094	-10000	0	-0.39	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.009	0.082	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.087	0.14	-10000	0	-0.39	75	75
GNAZ	-0.002	0.073	-10000	0	-0.41	17	17
E2/ER alpha (dimer)	-0.026	0.094	-10000	0	-0.29	62	62
STRN	0.009	0.025	-10000	0	-0.41	2	2
GNAL	-0.051	0.15	-10000	0	-0.41	80	80
PELP1	0.011	0	-10000	0	-10000	0	0
MAPK11	0.014	0.017	-10000	0	-0.22	3	3
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.051	-10000	0	-0.41	8	8
HBEGF	-0.1	0.18	-10000	0	-0.36	120	120
cAMP biosynthetic process	-0.048	0.089	-10000	0	-0.2	129	129
SRC	-0.077	0.18	-10000	0	-0.41	75	75
PI3K	0.013	0.031	-10000	0	-0.28	6	6
GNB1	0.011	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.032	0.085	-10000	0	-0.26	62	62
SOS1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.099	0.15	-10000	0	-0.36	112	112
Gs family/GTP	-0.048	0.091	-10000	0	-0.2	129	129
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.021	0.008	-10000	0	-10000	0	0
vasodilation	-0.053	0.17	-10000	0	-0.47	64	64
mol:DAG	-0.016	0.12	-10000	0	-0.36	57	57
Gs family/GDP/Gbeta gamma	-0.051	0.1	-10000	0	-0.29	66	66
MSN	0.017	0.062	-10000	0	-0.28	3	3
Gq family/GTP	-0.028	0.13	-10000	0	-0.39	56	56
mol:PI-3-4-5-P3	-0.071	0.24	-10000	0	-0.73	63	63
NRAS	0.011	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.053	0.17	0.47	64	-10000	0	64
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
RhoA/GDP	-0.033	0.091	-10000	0	-0.29	62	62
NOS3	-0.059	0.19	-10000	0	-0.52	64	64
GNA11	0.002	0.062	-10000	0	-0.41	12	12
MAPKKK cascade	-0.05	0.19	-10000	0	-0.54	64	64
E2/ER alpha (dimer)/PELP1/Src	-0.092	0.15	-10000	0	-0.41	75	75
ruffle organization	0.017	0.058	-10000	0	-0.26	3	3
ROCK2	0.012	0.065	-10000	0	-0.31	3	3
GNA14	-0.031	0.13	-10000	0	-0.41	54	54
GNA15	0.007	0.038	-10000	0	-0.33	7	7
GNA13	0.011	0	-10000	0	-10000	0	0
MMP9	-0.13	0.18	-10000	0	-0.4	119	119
MMP2	-0.076	0.18	-10000	0	-0.4	82	82

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.1	0.25	-10000	0	-0.66	43	43
PCK1	-0.12	0.33	-10000	0	-1.2	36	36
HNF4A	-0.16	0.33	-10000	0	-0.84	68	68
KCNJ11	-0.09	0.26	-10000	0	-0.7	35	35
AKT1	-0.049	0.14	-10000	0	-0.36	17	17
response to starvation	-0.01	0.032	-10000	0	-10000	0	0
DLK1	-0.15	0.34	-10000	0	-0.81	81	81
NKX2-1	-0.021	0.15	-10000	0	-0.48	2	2
ACADM	-0.1	0.26	-10000	0	-0.7	40	40
TAT	-0.098	0.2	-10000	0	-0.61	23	23
CEBPB	0.013	0.002	-10000	0	-10000	0	0
CEBPA	0.01	0.037	-10000	0	-0.38	5	5
TTR	-0.038	0.13	-10000	0	-0.63	6	6
PKLR	-0.11	0.25	-10000	0	-0.68	38	38
APOA1	-0.21	0.44	-10000	0	-1.2	71	71
CPT1C	-0.11	0.26	-10000	0	-0.71	46	46
ALAS1	-0.044	0.16	-10000	0	-10000	0	0
TFRC	-0.058	0.19	-10000	0	-0.62	8	8
FOXF1	0.008	0.046	-10000	0	-0.4	6	6
NF1	0.015	0.026	-10000	0	-0.41	2	2
HNF1A (dimer)	0.004	0.046	-10000	0	-0.35	8	8
CPT1A	-0.1	0.25	-10000	0	-0.66	43	43
HMGCS1	-0.1	0.25	-10000	0	-0.66	43	43
NR3C1	-0.067	0.16	-10000	0	-0.38	99	99
CPT1B	-0.1	0.25	-10000	0	-0.67	39	39
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.007	0.016	-10000	0	-10000	0	0
GCK	-0.17	0.34	-10000	0	-0.78	100	100
CREB1	0.003	0.041	-10000	0	-0.19	8	8
IGFBP1	-0.22	0.44	-10000	0	-1.1	90	90
PDX1	-0.054	0.15	-10000	0	-0.48	3	3
UCP2	-0.1	0.25	-10000	0	-0.66	43	43
ALDOB	-0.092	0.26	-10000	0	-0.68	36	36
AFP	-0.056	0.072	-10000	0	-0.4	10	10
BDH1	-0.1	0.25	-10000	0	-0.66	43	43
HADH	-0.089	0.26	-10000	0	-0.69	35	35
F2	-0.15	0.31	-10000	0	-0.87	40	40
HNF1A	0.004	0.046	-10000	0	-0.35	8	8
G6PC	0.007	0.066	-10000	0	-10000	0	0
SLC2A2	-0.057	0.17	-10000	0	-10000	0	0
INS	0.016	0.06	0.2	22	-10000	0	22
FOXA1	-0.21	0.16	-10000	0	-0.32	361	361
FOXA3	-0.057	0.16	-10000	0	-0.33	119	119
FOXA2	-0.11	0.3	-10000	0	-0.75	44	44
ABCC8	-0.18	0.38	-10000	0	-0.84	110	110
ALB	-0.063	0.14	-10000	0	-0.96	10	10

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.029	0.11	-9999	-0.36	23	23
SMAD6-7/SMURF1	0.021	0.019	-9999	-0.23	3	3
NOG	-0.019	0.096	-9999	-0.33	47	47
SMAD9	-0.059	0.17	-9999	-0.51	60	60
SMAD4	0.01	0.018	-9999	-0.41	1	1
SMAD5	-0.018	0.094	-9999	-0.3	30	30
BMP7/USAG1	-0.048	0.12	-9999	-0.26	124	124
SMAD5/SKI	-0.012	0.09	-9999	-0.29	28	28
SMAD1	0.034	0.014	-9999	-10000	0	0
BMP2	-0.025	0.12	-9999	-0.41	47	47
SMAD1/SMAD1/SMAD4	-0.001	0.012	-9999	-10000	0	0
BMPR1A	0.011	0	-9999	-10000	0	0
BMPR1B	-0.015	0.1	-9999	-0.41	34	34
BMPR1A-1B/BAMBI	-0.004	0.08	-9999	-0.25	46	46
AHSG	0	0.05	-9999	-0.33	12	12
CER1	0.004	0.005	-9999	-10000	0	0
BMP2-4/CER1	-0.018	0.092	-9999	-0.24	75	75
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.037	0.12	-9999	-0.34	39	39
BMP2-4 (homodimer)	-0.026	0.11	-9999	-0.29	75	75
RGMB	0.01	0.018	-9999	-0.41	1	1
BMP6/BMPR2/BMPR1A-1B	0.01	0.064	-9999	-0.2	43	43
RGMA	-0.082	0.18	-9999	-0.41	120	120
SMURF1	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.042	0.12	-9999	-0.34	41	41
BMP2-4/USAG1	-0.042	0.12	-9999	-0.24	136	136
SMAD6/SMURF1/SMAD5	-0.012	0.09	-9999	-0.3	24	24
SOSTDC1	-0.04	0.13	-9999	-0.36	72	72
BMP7/BMPR2/BMPR1A-1B	-0.008	0.088	-9999	-0.22	60	60
SKI	0.011	0	-9999	-10000	0	0
BMP6 (homodimer)	0.002	0.059	-9999	-0.41	11	11
HFE2	0.003	0.021	-9999	-0.33	2	2
ZFYVE16	0.011	0	-9999	-10000	0	0
MAP3K7	0.011	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.056	0.14	-9999	-0.27	141	141
SMAD5/SMAD5/SMAD4	-0.012	0.092	-9999	-0.29	28	28
MAPK1	0.011	0	-9999	-10000	0	0
TAK1/TAB family	-0.051	0.087	-9999	-0.31	35	35
BMP7 (homodimer)	-0.032	0.12	-9999	-0.37	62	62
NUP214	0.011	0	-9999	-10000	0	0
BMP6/FETUA	0.003	0.053	-9999	-0.25	23	23
SMAD1/SKI	0.038	0.014	-9999	-10000	0	0
SMAD6	0.01	0.018	-9999	-0.41	1	1
CTDSP2	0.011	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.02	0.097	-9999	-0.25	67	67
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.093	0.18	-9999	-0.41	135	135
BMPR2 (homodimer)	0.011	0	-9999	-10000	0	0
GADD34/PP1CA	0.022	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.002	0.071	-9999	-0.28	34	34
CHRDL1	-0.28	0.2	-9999	-0.41	371	371
ENDOFIN/SMAD1	0.038	0.014	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0	0.012	-9999	-10000	0	0
SMAD6/SMURF1	0.011	0	-9999	-10000	0	0
BAMBI	-0.007	0.083	-9999	-0.38	25	25
SMURF2	0.011	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.18	0.15	-9999	-0.26	388	388
BMP2-4/GREM1	-0.074	0.14	-9999	-0.26	185	185
SMAD7	0.009	0.025	-9999	-0.41	2	2
SMAD8A/SMAD8A/SMAD4	-0.05	0.16	-9999	-0.47	61	61
SMAD1/SMAD6	0.038	0.014	-9999	-10000	0	0
TAK1/SMAD6	0.016	0	-9999	-10000	0	0
BMP7	-0.032	0.12	-9999	-0.37	62	62
BMP6	0.002	0.059	-9999	-0.41	11	11
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.038	0.11	-9999	-0.34	38	38
PPM1A	0.011	0	-9999	-10000	0	0
SMAD1/SMURF2	0.038	0.014	-9999	-10000	0	0
SMAD7/SMURF1	0.015	0.018	-9999	-0.28	2	2
CTDSPL	0.011	0	-9999	-10000	0	0
PPP1CA	0.011	0	-9999	-10000	0	0
XIAP	0.011	0	-9999	-10000	0	0
CTDSP1	0.011	0	-9999	-10000	0	0
PPP1R15A	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.076	0.16	-9999	-0.42	69	69
CHRD	-0.063	0.16	-9999	-0.41	96	96
BMPR2	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.05	0.13	-9999	-0.37	41	41
BMP4	-0.014	0.097	-9999	-0.39	34	34
FST	-0.043	0.14	-9999	-0.4	70	70
BMP2-4/NOG	-0.03	0.11	-9999	-0.23	115	115
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.002	0.082	-9999	-0.36	8	8

×

Ephrin B reverse 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
EFNB2	0.009	0.031	-10000	0	-0.41	3	3
EPHB2	0.01	0.025	-10000	0	-0.33	3	3
EFNB1	0.016	0.037	-10000	0	-0.32	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.01	0.07	-10000	0	-0.35	4	4
Ephrin B2/EPHB1-2	0	0.067	-10000	0	-0.2	53	53
neuron projection morphogenesis	-0.021	0.056	-10000	0	-0.33	4	4
Ephrin B1/EPHB1-2/Tiam1	0.006	0.075	-10000	0	-0.2	48	48
DNM1	0.007	0.044	-10000	0	-0.41	6	6
cell-cell signaling	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.049	0.18	-10000	0	-0.52	70	70
YES1	-0.096	0.25	-10000	0	-0.75	70	70
Ephrin B1/EPHB1-2/NCK2	0.012	0.066	-10000	0	-0.18	41	41
PI3K	-0.05	0.19	-10000	0	-0.52	72	72
mol:GDP	0.005	0.075	-10000	0	-0.19	48	48
ITGA2B	0.005	0.05	-10000	0	-0.4	8	8
endothelial cell proliferation	0.014	0.021	-10000	0	-0.23	4	4
FYN	-0.096	0.25	-10000	0	-0.75	70	70
MAP3K7	-0.058	0.19	-10000	0	-0.55	70	70
FGR	-0.098	0.25	-10000	0	-0.75	70	70
TIAM1	0	0.067	-10000	0	-0.41	14	14
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
RGS3	0.011	0	-10000	0	-10000	0	0
cell adhesion	-0.074	0.2	-10000	0	-0.56	70	70
LYN	-0.096	0.25	-10000	0	-0.75	70	70
Ephrin B1/EPHB1-2/Src Family Kinases	-0.089	0.23	-10000	0	-0.7	70	70
Ephrin B1/EPHB1-2	-0.077	0.2	-10000	0	-0.6	70	70
SRC	-0.095	0.25	-10000	0	-0.75	70	70
ITGB3	-0.068	0.16	-10000	0	-0.41	102	102
EPHB1	-0.028	0.12	-10000	0	-0.4	52	52
EPHB4	0.01	0.018	-10000	0	-0.41	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.014	0.021	-10000	0	-0.23	4	4
alphaIIb/beta3 Integrin	-0.043	0.12	-10000	0	-0.28	110	110
BLK	-0.095	0.25	-10000	0	-0.75	70	70
HCK	-0.095	0.25	-10000	0	-0.75	70	70
regulation of stress fiber formation	-0.011	0.066	0.18	41	-10000	0	41
MAPK8	-0.043	0.18	-10000	0	-0.5	70	70
Ephrin B1/EPHB1-2/RGS3	0.012	0.066	-10000	0	-0.18	41	41
endothelial cell migration	-0.056	0.16	-10000	0	-0.46	71	71
NCK2	0.011	0	-10000	0	-10000	0	0
PTPN13	-0.059	0.18	-10000	0	-0.52	70	70
regulation of focal adhesion formation	-0.011	0.066	0.18	41	-10000	0	41
chemotaxis	-0.011	0.066	0.18	41	-10000	0	41
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
Rac1/GTP	-0.021	0.057	-10000	0	-0.34	4	4
angiogenesis	-0.077	0.2	-10000	0	-0.6	70	70
LCK	-0.095	0.25	-10000	0	-0.75	70	70

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.005	0.067	-9999	-0.25	30	30
alphaM/beta2 Integrin/GPIbA	0.014	0.041	-9999	-0.27	7	7
alphaM/beta2 Integrin/proMMP-9	-0.062	0.1	-9999	-0.22	55	55
PLAUR	0.009	0.025	-9999	-0.33	3	3
HMGB1	0.009	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	0.018	0.033	-9999	-0.24	5	5
AGER	0.008	0.021	-9999	-0.4	1	1
RAP1A	0.011	0	-9999	-10000	0	0
SELPLG	0.01	0.021	-9999	-0.33	2	2
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.019	0.056	-9999	-0.27	3	3
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	222	222
CYR61	-0.027	0.12	-9999	-0.41	49	49
TLN1	0.011	0	-9999	-10000	0	0
Rap1/GTP	-0.029	0.061	-9999	-0.26	15	15
RHOA	0.011	0	-9999	-10000	0	0
P-selectin oligomer	-0.15	0.2	-9999	-0.41	207	207
MYH2	-0.031	0.11	-9999	-0.31	36	36
MST1R	-0.021	0.1	-9999	-0.33	51	51
leukocyte activation during inflammatory response	-0.015	0.05	-9999	-0.22	14	14
APOB	-0.001	0.053	-9999	-0.39	10	10
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.01	0.091	-9999	-0.41	27	27
JAM3	-0.1	0.19	-9999	-0.41	145	145
GP1BA	0.008	0.029	-9999	-0.38	3	3
alphaM/beta2 Integrin/CTGF	0.011	0.052	-9999	-0.24	19	19
alphaM/beta2 Integrin	-0.023	0.084	-9999	-0.23	40	40
JAM3 homodimer	-0.1	0.19	-9999	-0.41	145	145
ICAM2	0.011	0	-9999	-10000	0	0
ICAM1	0.008	0.029	-9999	-0.33	4	4
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.022	0.084	-9999	-0.23	40	40
cell adhesion	0.014	0.04	-9999	-0.27	7	7
NFKB1	0.018	0.086	-9999	-0.3	19	19
THY1	0.011	0	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
Lipoprotein(a)	-0.006	0.055	-9999	-0.2	41	41
alphaM/beta2 Integrin/LRP/tPA	-0.001	0.08	-9999	-0.21	62	62
IL6	0.012	0.13	-9999	-0.53	23	23
ITGB2	0.006	0.034	-9999	-0.33	5	5
elevation of cytosolic calcium ion concentration	0.021	0.036	-9999	-0.22	4	4
alphaM/beta2 Integrin/JAM2/JAM3	-0.11	0.17	-9999	-0.28	247	247
JAM2	-0.14	0.2	-9999	-0.41	193	193
alphaM/beta2 Integrin/ICAM1	0.01	0.062	-9999	-0.36	3	3
alphaM/beta2 Integrin/uPA/Plg	0	0.076	-9999	-0.21	52	52
RhoA/GTP	-0.034	0.11	-9999	-0.28	61	61
positive regulation of phagocytosis	-0.02	0.055	-9999	-0.27	6	6
Ron/MSP	-0.009	0.072	-9999	-0.22	58	58
alphaM/beta2 Integrin/uPAR/uPA	0.022	0.036	-9999	-0.22	4	4
alphaM/beta2 Integrin/uPAR	0.016	0.036	-9999	-0.23	7	7
PLAU	0.009	0.025	-9999	-0.33	3	3
PLAT	-0.035	0.13	-9999	-0.41	59	59
actin filament polymerization	-0.029	0.1	-9999	-0.3	36	36
MST1	0.007	0.038	-9999	-0.33	7	7
alphaM/beta2 Integrin/lipoprotein(a)	0.003	0.057	-9999	-0.22	14	14
TNF	0.011	0.11	-9999	-0.59	3	3
RAP1B	0.011	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	0.016	0.037	-9999	-0.22	8	8
fibrinolysis	-0.001	0.075	-9999	-0.21	52	52
HCK	0.007	0.038	-9999	-0.33	7	7
dendritic cell antigen processing and presentation	-0.022	0.084	-9999	-0.23	40	40
VTN	-0.047	0.14	-9999	-0.41	74	74
alphaM/beta2 Integrin/CYR61	-0.005	0.08	-9999	-0.24	52	52
LPA	-0.012	0.079	-9999	-0.33	32	32
LRP1	0.009	0.025	-9999	-0.41	2	2
cell migration	-0.059	0.1	-9999	-0.25	41	41
FN1	0.007	0.04	-9999	-0.41	5	5
alphaM/beta2 Integrin/Thy1	0.018	0.033	-9999	-0.24	5	5
MPO	0.005	0.041	-9999	-0.33	8	8
KNG1	-0.01	0.07	-9999	-0.33	25	25
RAP1/GDP	0.015	0	-9999	-10000	0	0
ROCK1	-0.026	0.11	-9999	-0.31	36	36
ELA2	0	0	-9999	-10000	0	0
PLG	-0.032	0.12	-9999	-0.4	55	55
CTGF	0	0.067	-9999	-0.41	14	14
alphaM/beta2 Integrin/Hck	0.015	0.044	-9999	-0.27	8	8
ITGAM	0.006	0.038	-9999	-0.37	5	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.063	0.12	-9999	-0.2	210	210
HP	-0.1	0.17	-9999	-0.35	170	170
leukocyte adhesion	-0.11	0.13	-9999	-0.34	104	104
SELP	-0.15	0.2	-9999	-0.41	207	207

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.014	0.076	-9999	-0.24	54	54
EFNA5	-0.003	0.076	-9999	-0.4	19	19
FYN	-0.006	0.069	-9999	-0.21	53	53
neuron projection morphogenesis	-0.014	0.076	-9999	-0.24	54	54
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.014	0.077	-9999	-0.24	54	54
EPHA5	-0.023	0.1	-9999	-0.41	37	37

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.032	0.13	-9999	-0.41	55	55
GNB1/GNG2	-0.048	0.14	-9999	-0.4	41	41
mol:DAG	-0.039	0.13	-9999	-0.41	32	32
PLCG1	-0.04	0.13	-9999	-0.42	32	32
YES1	-0.053	0.14	-9999	-0.43	38	38
FZD3	0.011	0	-9999	-10000	0	0
FZD6	0.01	0.018	-9999	-0.41	1	1
G protein	-0.04	0.13	-9999	-0.43	32	32
MAP3K7	-0.12	0.14	-9999	-0.33	122	122
mol:Ca2+	-0.038	0.12	-9999	-0.4	32	32
mol:IP3	-0.039	0.13	-9999	-0.41	32	32
NLK	-0.005	0.009	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CAMK2A	-0.14	0.15	-9999	-0.36	122	122
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.062	0.15	-9999	-0.42	43	43
CSNK1A1	0.011	0	-9999	-10000	0	0
GNAS	-0.053	0.14	-9999	-0.43	38	38
GO:0007205	-0.039	0.13	-9999	-0.4	33	33
WNT6	-0.031	0.12	-9999	-0.38	58	58
WNT4	-0.088	0.18	-9999	-0.41	128	128
NFAT1/CK1 alpha	-0.051	0.14	-9999	-0.41	44	44
GNG2	0.003	0.056	-9999	-0.4	10	10
WNT5A	-0.003	0.075	-9999	-0.41	18	18
WNT11	-0.03	0.12	-9999	-0.35	63	63
CDC42	-0.044	0.13	-9999	-0.4	38	38

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.077	0.17	-9999	-0.31	169	169
MAP3K8	0.006	0.032	-9999	-0.41	3	3
FOS	-0.044	0.12	-9999	-0.38	26	26
PRKCA	-0.02	0.1	-9999	-0.41	36	36
PTPN7	0.005	0.037	-9999	-0.34	6	6
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.016	0.099	-9999	-0.41	32	32
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	0.015	0.013	-9999	-10000	0	0
MAPK3	-0.017	0.069	-9999	-0.25	5	5
MAP2K1	-0.038	0.14	-9999	-0.4	64	64
ELK1	0.005	0.01	-9999	-10000	0	0
BRAF	-0.034	0.14	-9999	-0.38	64	64
mol:GTP	-0.001	0.002	-9999	-0.005	167	167
MAPK1	-0.017	0.069	-9999	-0.25	5	5
RAF1	-0.034	0.14	-9999	-0.38	64	64
KRAS	0.01	0.015	-9999	-0.33	1	1

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.04	0.1	-9999	-0.32	16	16
NF kappa B1 p50/RelA/I kappa B alpha	-0.013	0.092	-9999	-0.27	15	15
alphaV/beta3 Integrin/Osteopontin/Src	-0.043	0.1	-9999	-0.21	155	155
AP1	-0.081	0.15	-9999	-0.34	98	98
ILK	-0.051	0.11	-9999	-0.33	18	18
bone resorption	-0.029	0.1	-9999	-0.29	31	31
PTK2B	0.011	0	-9999	-10000	0	0
PYK2/p130Cas	-0.034	0.098	-9999	-0.3	17	17
ITGAV	0.014	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.004	0.058	-9999	-0.28	22	22
alphaV/beta3 Integrin/Osteopontin	-0.066	0.12	-9999	-0.24	101	101
MAP3K1	-0.052	0.11	-9999	-0.32	20	20
JUN	0.006	0.047	-9999	-0.41	7	7
MAPK3	-0.037	0.1	-9999	-0.32	16	16
MAPK1	-0.037	0.1	-9999	-0.32	16	16
Rac1/GDP	0.008	0	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAPK8	-0.043	0.1	-9999	-0.32	23	23
ITGB3	-0.064	0.16	-9999	-0.4	102	102
NFKBIA	-0.026	0.099	-9999	-0.3	16	16
FOS	-0.12	0.19	-9999	-0.41	167	167
CD44	0.005	0.05	-9999	-0.4	8	8
CHUK	0.011	0	-9999	-10000	0	0
PLAU	-0.021	0.095	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.046	0.06	-9999	-0.26	15	15
BCAR1	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.032	0.11	-9999	-0.27	102	102
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.052	0.11	-9999	-0.32	21	21
VAV3	-0.079	0.12	-9999	-0.3	68	68
MAP3K14	-0.049	0.11	-9999	-0.32	20	20
ROCK2	0	0.067	-9999	-0.41	14	14
SPP1	-0.082	0.15	-9999	-0.32	155	155
RAC1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.068	0.11	-9999	-0.27	68	68
MMP2	-0.073	0.15	-9999	-0.48	36	36

×

IL4-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
BCL2L1	-0.24	0.37	-10000	0	-1	60	60
STAT6 (cleaved dimer)	-0.27	0.34	-10000	0	-0.91	87	87
IGHG1	-0.085	0.14	-10000	0	-0.35	23	23
IGHG3	-0.24	0.36	-10000	0	-0.9	83	83
AKT1	-0.1	0.2	-10000	0	-0.59	22	22
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.064	0.16	-10000	0	-0.58	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.12	0.23	-10000	0	-0.62	42	42
THY1	-0.24	0.37	-10000	0	-1	61	61
MYB	-0.022	0.1	-10000	0	-0.33	53	53
HMGA1	-0.038	0.12	-10000	0	-0.33	78	78
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.23	-10000	0	-0.59	47	47
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.1	0.2	-10000	0	-0.6	20	20
SP1	0.017	0.002	-10000	0	-10000	0	0
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
SOCS5	0.017	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.22	0.37	-10000	0	-0.96	70	70
SOCS1	-0.14	0.26	-10000	0	-0.68	52	52
SOCS3	-0.1	0.21	-10000	0	-0.94	6	6
FCER2	-0.18	0.3	-10000	0	-0.81	48	48
PARP14	0.012	0.002	-10000	0	-10000	0	0
CCL17	-0.24	0.37	-10000	0	-1	54	54
GRB2	0.011	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.08	0.16	-10000	0	-0.58	7	7
T cell proliferation	-0.24	0.38	-10000	0	-1	66	66
IL4R/JAK1	-0.24	0.38	-10000	0	-1	62	62
EGR2	-0.27	0.46	-10000	0	-1.2	71	71
JAK2	-0.009	0.06	-10000	0	-0.43	9	9
JAK3	0.012	0.03	-10000	0	-0.33	4	4
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
JAK1	0.007	0.027	-10000	0	-0.4	2	2
COL1A2	-0.078	0.18	-10000	0	-1.4	5	5
CCL26	-0.24	0.37	-10000	0	-1	58	58
IL4R	-0.25	0.4	-10000	0	-1.1	62	62
PTPN6	0.017	0.018	-10000	0	-0.31	1	1
IL13RA2	-0.24	0.38	-10000	0	-1	61	61
IL13RA1	-0.002	0.027	-10000	0	-10000	0	0
IRF4	-0.061	0.22	-10000	0	-1.1	18	18
ARG1	-0.054	0.11	-10000	0	-10000	0	0
CBL	-0.12	0.22	-10000	0	-0.56	41	41
GTF3A	0.018	0.001	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
IL13RA1/JAK2	-0.008	0.051	-10000	0	-0.28	9	9
IRF4/BCL6	-0.054	0.2	-10000	0	-1	18	18
CD40LG	0.007	0.064	-10000	0	-0.42	12	12
MAPK14	-0.12	0.22	-10000	0	-0.6	32	32
mitosis	-0.097	0.2	-10000	0	-0.56	22	22
STAT6	-0.27	0.42	-10000	0	-1.1	82	82
SPI1	0.011	0.025	-10000	0	-0.32	3	3
RPS6KB1	-0.089	0.19	-10000	0	-0.57	17	17
STAT6 (dimer)	-0.27	0.42	-10000	0	-1.1	82	82
STAT6 (dimer)/PARP14	-0.25	0.39	-10000	0	-0.98	82	82
mast cell activation	0.006	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.096	0.19	-10000	0	-0.61	13	13
FRAP1	-0.1	0.2	-10000	0	-0.59	22	22
LTA	-0.24	0.37	-10000	0	-1	63	63
FES	0.01	0.018	-10000	0	-0.41	1	1
T-helper 1 cell differentiation	0.26	0.41	1	82	-10000	0	82
CCL11	-0.25	0.39	-10000	0	-1	74	74
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.095	0.19	-10000	0	-0.59	15	15
IL2RG	0.009	0.048	-10000	0	-0.36	9	9
IL10	-0.24	0.37	-10000	0	-1	60	60
IRS1	-0.031	0.13	-10000	0	-0.41	54	54
IRS2	-0.042	0.14	-10000	0	-0.41	69	69
IL4	-0.059	0.1	-10000	0	-10000	0	0
IL5	-0.24	0.37	-10000	0	-1	60	60
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.21	0.32	-10000	0	-0.82	65	65
COL1A1	-0.075	0.16	-10000	0	-1.5	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.24	0.38	-10000	0	-1.1	58	58
IL2R gamma/JAK3	0.015	0.045	-10000	0	-0.3	10	10
TFF3	-0.3	0.43	-10000	0	-1.1	86	86
ALOX15	-0.25	0.38	-10000	0	-1.1	59	59
MYBL1	0.011	0	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.21	0.32	-10000	0	-0.8	74	74
SHC1	0.011	0	-10000	0	-10000	0	0
CEBPB	0.013	0.003	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.12	0.21	-10000	0	-0.56	36	36
mol:PI-3-4-5-P3	-0.1	0.2	-10000	0	-0.59	22	22
PI3K	-0.11	0.21	-10000	0	-0.65	19	19
DOK2	0.008	0.031	-10000	0	-0.35	4	4
ETS1	0.017	0.02	-10000	0	-0.38	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.072	0.16	-10000	0	-0.58	6	6
ITGB3	-0.37	0.57	-10000	0	-1.3	119	119
PIGR	-0.33	0.47	-10000	0	-1.2	95	95
IGHE	0.019	0.033	-10000	0	-10000	0	0
MAPKKK cascade	-0.071	0.16	-10000	0	-0.57	6	6
BCL6	0.01	0.018	-10000	0	-0.41	1	1
OPRM1	-0.24	0.37	-10000	0	-1	62	62
RETNLB	-0.24	0.37	-10000	0	-1	58	58
SELP	-0.52	0.66	-10000	0	-1.3	215	215
AICDA	-0.23	0.36	-10000	0	-0.98	61	61

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.089	0.12	-9999	-0.22	228	228
TP53	-0.023	0.03	-9999	-0.34	1	1
Senescence	-0.023	0.03	-9999	-0.34	1	1
Apoptosis	-0.023	0.03	-9999	-0.34	1	1
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.047	0.055	-9999	-10000	0	0
MDM4	0.011	0	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.006	0.074	-9999	-0.23	45	45
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.068	-9999	-0.26	5	5
AP1	-0.08	0.11	-9999	-0.36	50	50
mol:PIP3	-0.03	0.069	-9999	-0.32	16	16
AKT1	0.029	0.056	-9999	-0.27	8	8
PTK2B	0.006	0.059	-9999	-0.21	27	27
RHOA	0.019	0.03	-9999	-10000	0	0
PIK3CB	0.011	0	-9999	-10000	0	0
mol:Ca2+	0.005	0.063	-9999	-0.19	29	29
MAGI3	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
apoptosis	-0.011	0.086	-9999	-0.23	63	63
HRAS/GDP	0.008	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.01	0.065	-9999	-0.23	17	17
NF kappa B1 p50/RelA	-0.025	0.068	-9999	-0.32	11	11
endothelial cell migration	-0.01	0.12	-9999	-0.44	39	39
ADCY4	-0.044	0.14	-9999	-0.37	56	56
ADCY5	-0.072	0.16	-9999	-0.38	78	78
ADCY6	-0.035	0.13	-9999	-0.34	48	48
ADCY7	-0.035	0.13	-9999	-0.34	48	48
ADCY1	-0.044	0.14	-9999	-0.37	57	57
ADCY2	-0.14	0.19	-9999	-0.4	143	143
ADCY3	-0.036	0.13	-9999	-0.34	50	50
ADCY8	-0.039	0.13	-9999	-0.34	48	48
ADCY9	-0.064	0.16	-9999	-0.38	86	86
GSK3B	0.011	0.056	-9999	-0.22	15	15
arachidonic acid secretion	-0.04	0.13	-9999	-0.39	38	38
GNG2	0.003	0.056	-9999	-0.4	10	10
TRIP6	0.014	0.037	-9999	-0.35	5	5
GNAO1	-0.061	0.14	-9999	-0.26	164	164
HRAS	0.011	0	-9999	-10000	0	0
NFKBIA	0.009	0.076	-9999	-0.23	31	31
GAB1	0.008	0.036	-9999	-0.41	4	4
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.14	-9999	-0.86	14	14
JUN	0.006	0.047	-9999	-0.41	7	7
LPA/LPA2/NHERF2	0.012	0.022	-9999	-0.18	3	3
TIAM1	-0.024	0.16	-9999	-1	14	14
PIK3R1	0.007	0.04	-9999	-0.41	5	5
mol:IP3	0.005	0.064	-9999	-0.19	29	29
PLCB3	0.018	0.02	-9999	-0.15	3	3
FOS	-0.12	0.19	-9999	-0.41	167	167
positive regulation of mitosis	-0.04	0.13	-9999	-0.39	38	38
LPA/LPA1-2-3	-0.013	0.089	-9999	-0.22	63	63
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.011	0	-9999	-10000	0	0
stress fiber formation	0.007	0.068	-9999	-0.26	15	15
GNAZ	-0.004	0.085	-9999	-0.25	54	54
EGFR/PI3K-beta/Gab1	-0.031	0.071	-9999	-0.33	16	16
positive regulation of dendritic cell cytokine production	-0.017	0.087	-9999	-0.22	63	63
LPA/LPA2/MAGI-3	0.012	0.022	-9999	-0.18	3	3
ARHGEF1	0.015	0.061	-9999	-0.37	5	5
GNAI2	0.003	0.072	-9999	-0.25	39	39
GNAI3	0.003	0.072	-9999	-0.25	39	39
GNAI1	0	0.078	-9999	-0.25	46	46
LPA/LPA3	-0.019	0.081	-9999	-0.26	52	52
LPA/LPA2	0.005	0.027	-9999	-0.22	3	3
LPA/LPA1	-0.007	0.084	-9999	-0.3	39	39
HB-EGF/EGFR	-0.064	0.1	-9999	-0.2	100	100
HBEGF	-0.078	0.12	-9999	-0.22	222	222
mol:DAG	0.005	0.064	-9999	-0.19	29	29
cAMP biosynthetic process	-0.067	0.15	-9999	-0.28	142	142
NFKB1	0.01	0.018	-9999	-0.41	1	1
SRC	0.011	0	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
LYN	0.009	0.076	-9999	-0.23	31	31
GNAQ	-0.002	0.06	-9999	-0.22	29	29
LPAR2	0.009	0.025	-9999	-0.33	3	3
LPAR3	-0.026	0.11	-9999	-0.37	52	52
LPAR1	-0.006	0.086	-9999	-0.45	17	17
IL8	-0.071	0.11	-9999	-0.34	38	38
PTK2	-0.004	0.084	-9999	-0.27	19	19
Rac1/GDP	0.008	0	-9999	-10000	0	0
CASP3	-0.011	0.086	-9999	-0.23	63	63
EGFR	0	0.066	-9999	-0.4	14	14
PLCG1	-0.009	0.075	-9999	-0.22	46	46
PLD2	-0.004	0.084	-9999	-0.38	9	9
G12/G13	0.01	0.066	-9999	-0.22	39	39
PI3K-beta	-0.014	0.049	-9999	-0.3	9	9
cell migration	-0.014	0.049	-9999	-0.24	17	17
SLC9A3R2	0.011	0	-9999	-10000	0	0
PXN	0.007	0.069	-9999	-0.27	15	15
HRAS/GTP	-0.042	0.14	-9999	-0.4	38	38
RAC1	0.011	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	222	222
PRKCE	0.011	0.001	-9999	-10000	0	0
PRKCD	0.01	0.061	-9999	-0.23	5	5
Gi(beta/gamma)	-0.034	0.12	-9999	-0.33	49	49
mol:LPA	-0.004	0.034	-9999	-0.16	22	22
TRIP6/p130 Cas/FAK1/Paxillin	-0.023	0.072	-9999	-0.38	10	10
MAPKKK cascade	-0.04	0.13	-9999	-0.39	38	38
contractile ring contraction involved in cytokinesis	0.019	0.03	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.025	0.095	-9999	-0.24	79	79
GNA15	-0.003	0.06	-9999	-0.22	28	28
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
MAPT	0.009	0.067	-9999	-0.23	17	17
GNA11	-0.007	0.066	-9999	-0.22	40	40
Rac1/GTP	-0.002	0.15	-9999	-0.91	14	14
MMP2	-0.01	0.13	-9999	-0.44	39	39

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.033	0.1	0.34	16	-10000	0	16
GNAI2	0.011	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.008	0.036	-10000	0	-0.19	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.1	0.18	-10000	0	-0.41	143	143
RhoA/GTP	-0.033	0.1	-10000	0	-0.35	16	16
negative regulation of cAMP metabolic process	-0.042	0.11	-10000	0	-0.21	147	147
GNAZ	-0.002	0.073	-10000	0	-0.41	17	17
GNAI3	0.011	0	-10000	0	-10000	0	0
GNA12	0.011	0	-10000	0	-10000	0	0
S1PR5	0	0.063	-10000	0	-0.35	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.042	0.11	-10000	0	-0.21	147	147
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.051	-10000	0	-0.41	8	8

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.002	0.071	-9999	-0.28	33	33
PDGFRB	-0.008	0.086	-9999	-0.42	23	23
SPHK1	-0.013	0.024	-9999	-10000	0	0
mol:S1P	-0.016	0.03	-9999	-10000	0	0
S1P1/S1P/Gi	-0.081	0.19	-9999	-0.42	90	90
GNAO1	-0.1	0.19	-9999	-0.41	143	143
PDGFB-D/PDGFRB/PLCgamma1	-0.066	0.18	-9999	-0.39	94	94
PLCG1	-0.07	0.18	-9999	-0.4	91	91
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.008	0.086	-9999	-0.42	23	23
GNAI2	0.011	0.004	-9999	-10000	0	0
GNAI3	0.01	0.004	-9999	-10000	0	0
GNAI1	0.004	0.052	-9999	-0.42	8	8
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.001	0.06	-9999	-0.24	33	33
S1P1/S1P	-0.023	0.065	-9999	-0.27	15	15
negative regulation of cAMP metabolic process	-0.078	0.18	-9999	-0.41	90	90
MAPK3	-0.091	0.23	-9999	-0.55	85	85
calcium-dependent phospholipase C activity	-0.002	0.003	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
KDR	-0.015	0.1	-9999	-0.41	33	33
PLCB2	0.004	0.069	-9999	-0.24	14	14
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.02	0.055	-9999	-0.23	14	14
receptor internalization	-0.022	0.062	-9999	-0.25	15	15
PTGS2	-0.13	0.33	-9999	-0.98	65	65
Rac1/GTP	-0.02	0.055	-9999	-0.23	14	14
RHOA	0.011	0	-9999	-10000	0	0
VEGFA	0.011	0.002	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.078	0.18	-9999	-0.41	90	90
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.003	0.074	-9999	-0.42	17	17
MAPK1	-0.091	0.23	-9999	-0.55	85	85
S1P1/S1P/PDGFB-D/PDGFRB	-0.006	0.099	-9999	-0.32	27	27
ABCC1	0.01	0.002	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.019	0.058	0.2	52	-10000	0	52
RFC1	0.019	0.058	0.2	52	-10000	0	52
PRKDC	0.019	0.058	0.2	52	-10000	0	52
RIPK1	0.011	0.002	-10000	0	-10000	0	0
CASP7	-0.002	0.016	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.019	0.065	0.19	62	-0.21	5	67
MAP2K4	0.037	0.056	-10000	0	-0.24	12	12
mol:ceramide	0.028	0.045	-10000	0	-0.24	4	4
GSN	0.017	0.062	0.2	51	-0.22	5	56
FASLG/FAS/FADD/FAF1/Caspase 8	0.038	0.056	-10000	0	-0.25	2	2
FAS	0.007	0.04	-10000	0	-0.41	5	5
BID	0.001	0.016	0.27	2	-10000	0	2
MAP3K1	0.034	0.038	-10000	0	-10000	0	0
MAP3K7	0.011	0.002	-10000	0	-10000	0	0
RB1	0.018	0.06	0.2	51	-0.22	2	53
CFLAR	0.011	0.002	-10000	0	-10000	0	0
HGF/MET	-0.064	0.14	-10000	0	-0.26	166	166
ARHGDIB	0.019	0.058	0.2	52	-10000	0	52
FADD	0.011	0.003	-10000	0	-10000	0	0
actin filament polymerization	-0.017	0.062	0.22	5	-0.2	51	56
NFKB1	-0.009	0.044	-10000	0	-0.65	1	1
MAPK8	0.036	0.086	-10000	0	-0.41	16	16
DFFA	0.019	0.058	0.2	52	-10000	0	52
DNA fragmentation during apoptosis	0.019	0.058	0.2	52	-10000	0	52
FAS/FADD/MET	0.017	0.038	-10000	0	-0.21	14	14
CFLAR/RIP1	0.015	0.003	-10000	0	-10000	0	0
FAIM3	0.009	0.029	-10000	0	-0.38	3	3
FAF1	0.011	0.004	-10000	0	-10000	0	0
PARP1	0.019	0.058	0.2	52	-10000	0	52
DFFB	0.019	0.058	0.2	52	-10000	0	52
CHUK	-0.008	0.039	-10000	0	-0.6	1	1
FASLG	0.003	0.054	-10000	0	-0.36	12	12
FAS/FADD	0.014	0.029	-10000	0	-0.28	5	5
HGF	-0.076	0.17	-10000	0	-0.41	112	112
LMNA	0.018	0.054	0.18	52	-10000	0	52
CASP6	0.019	0.058	0.2	52	-10000	0	52
CASP10	0.01	0.026	-10000	0	-0.41	2	2
CASP3	0.022	0.068	0.23	52	-10000	0	52
PTPN13	-0.043	0.14	-10000	0	-0.41	70	70
CASP8	0.001	0.02	0.33	2	-10000	0	2
IL6	-0.005	0.2	-10000	0	-1.1	17	17
MET	0.005	0.049	-10000	0	-0.37	9	9
ICAD/CAD	0.018	0.054	0.18	52	-10000	0	52
FASLG/FAS/FADD/FAF1/Caspase 10	0.028	0.046	-10000	0	-0.24	4	4
activation of caspase activity by cytochrome c	0.001	0.016	0.27	2	-10000	0	2
PAK2	0.019	0.058	0.2	52	-10000	0	52
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.01	0.015	-9999	-0.33	1	1
GPC2	-0.014	0.089	-9999	-0.33	40	40
GPC2/Midkine	-0.001	0.062	-9999	-0.22	41	41
neuron projection morphogenesis	-0.001	0.061	-9999	-0.22	41	41

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.015	0	-9999	0	-10000	0	0
ARNO/beta Arrestin1-2	-0.02	0.068	-9999	0	-0.34	1	1
EGFR	0	0.066	-9999	0	-0.4	14	14
EPHA2	0.011	0	-9999	0	-10000	0	0
USP6	0.011	0	-9999	0	-10000	0	0
IQSEC1	0.01	0.018	-9999	0	-0.41	1	1
EGFR/EGFR/EGF/EGF	-0.003	0.069	-9999	0	-0.25	38	38
ARRB2	0.008	0.002	-9999	0	-10000	0	0
mol:GTP	0.015	0.011	-9999	0	-0.14	1	1
ARRB1	0.009	0.025	-9999	0	-0.41	2	2
FBXO8	0.011	0	-9999	0	-10000	0	0
TSHR	-0.006	0.071	-9999	0	-0.34	23	23
EGF	-0.006	0.073	-9999	0	-0.34	25	25
somatostatin receptor activity	0	0	-9999	0	-0.001	75	75
ARAP2	0.009	0.031	-9999	0	-0.41	3	3
mol:GDP	-0.046	0.091	-9999	0	-0.22	81	81
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	50	50
ITGA2B	0.005	0.05	-9999	0	-0.4	8	8
ARF6	0.011	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.027	0.017	-9999	0	-0.2	2	2
ADAP1	0.011	0	-9999	0	-10000	0	0
KIF13B	0.011	0	-9999	0	-10000	0	0
HGF/MET	-0.049	0.12	-9999	0	-0.28	118	118
PXN	0.011	0	-9999	0	-10000	0	0
ARF6/GTP	-0.041	0.095	-9999	0	-0.22	71	71
EGFR/EGFR/EGF/EGF/ARFGEP100	0.006	0.059	-9999	0	-0.24	17	17
ADRB2	-0.063	0.16	-9999	0	-0.41	95	95
receptor agonist activity	0	0	-9999	0	0	78	78
actin filament binding	0	0	-9999	0	0	75	75
SRC	0.011	0	-9999	0	-10000	0	0
ITGB3	-0.068	0.16	-9999	0	-0.41	102	102
GNAQ	0.009	0.026	-9999	0	-0.41	2	2
EFA6/PI-4-5-P2	0	0	-9999	0	-0.001	62	62
ARF6/GDP	0.017	0.048	-9999	0	-0.28	5	5
ARF6/GDP/GULP/ACAP1	-0.047	0.11	-9999	0	-0.3	58	58
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.017	0.091	-9999	0	-0.2	107	107
ACAP1	0.008	0.036	-9999	0	-0.36	5	5
ACAP2	0.01	0.018	-9999	0	-0.41	1	1
LHCGR/beta Arrestin2	0.001	0.004	-9999	0	-10000	0	0
EFNA1	0.01	0.021	-9999	0	-0.33	2	2
HGF	-0.076	0.17	-9999	0	-0.41	112	112
CYTH3	0.009	0	-9999	0	-10000	0	0
CYTH2	0.007	0.002	-9999	0	-10000	0	0
NCK1	0.009	0.025	-9999	0	-0.41	2	2
fibronectin binding	0	0	-9999	0	0	64	64
endosomal lumen acidification	0	0	0	1	0	46	47
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.036	0.13	-9999	0	-0.41	61	61
GNAQ/ARNO	0.012	0.013	-9999	0	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	0	2	2
PIP3-E	0	0	-9999	0	0	13	13
MET	0.005	0.049	-9999	0	-0.37	9	9
GNA14	-0.031	0.13	-9999	0	-0.41	54	54
GNA15	0.007	0.038	-9999	0	-0.33	7	7
GIT1	0.011	0	-9999	0	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	0	-0.001	62	62
GNA11	0.002	0.062	-9999	0	-0.41	12	12
LHCGR	0.001	0.003	-9999	0	-10000	0	0
AGTR1	-0.086	0.17	-9999	0	-0.41	122	122
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.004	-9999	0	-10000	0	0
IPCEF1/ARNO	0.006	0.044	-9999	0	-0.31	1	1
alphaIIb/beta3 Integrin	-0.043	0.12	-9999	0	-0.28	110	110

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.007	0.049	-10000	0	-1.1	1	1
VDR	0.003	0.052	-10000	0	-0.33	13	13
FAM120B	0.011	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.01	0.086	-10000	0	-0.26	22	22
RXRs/LXRs/DNA/Oxysterols	0.016	0.087	-10000	0	-0.45	2	2
MED1	0.011	0	-10000	0	-10000	0	0
mol:9cRA	0.003	0.007	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.026	0.11	-10000	0	-0.21	129	129
RXRs/NUR77	-0.011	0.1	-10000	0	-0.21	98	98
RXRs/PPAR	-0.007	0.091	-10000	0	-0.2	95	95
NCOR2	0.011	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.003	0.036	-10000	0	-0.22	13	13
RARs/VDR/DNA/Vit D3	0.018	0.039	-10000	0	-0.19	11	11
RARA	0.011	0	-10000	0	-10000	0	0
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
VDR/VDR/DNA	0.003	0.052	-10000	0	-0.33	13	13
RARs/RARs/DNA/9cRA	0.018	0.03	-10000	0	-0.19	11	11
RARG	0.011	0	-10000	0	-10000	0	0
RPS6KB1	0.012	0.03	-10000	0	-0.4	1	1
RARs/THRs/DNA/SMRT	-0.026	0.1	-10000	0	-0.2	129	129
THRA	0.002	0.059	-10000	0	-0.41	11	11
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.003	0.036	-10000	0	-0.22	13	13
RXRs/PPAR/9cRA/PGJ2/DNA	0	0.085	0.28	1	-0.21	71	72
NR1H4	-0.009	0.061	-10000	0	-0.33	19	19
RXRs/LXRs/DNA	0.017	0.084	-10000	0	-0.23	21	21
NR1H2	0.014	0.006	-10000	0	-10000	0	0
NR1H3	0.014	0.015	-10000	0	-0.32	1	1
RXRs/VDR/DNA/Vit D3	-0.001	0.082	-10000	0	-0.19	72	72
NR4A1	-0.016	0.1	-10000	0	-0.41	35	35
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.003	0.072	-10000	0	-0.18	70	70
RXRG	-0.046	0.15	-10000	0	-0.4	79	79
RXR alpha/CCPG	0.018	0.007	-10000	0	-10000	0	0
RXRA	0.014	0.006	-10000	0	-10000	0	0
RXRB	0.015	0.005	-10000	0	-10000	0	0
THRB	-0.078	0.17	-10000	0	-0.41	115	115
PPARG	-0.012	0.096	-10000	0	-0.41	30	30
PPARD	0.011	0	-10000	0	-10000	0	0
TNF	0.011	0.11	-10000	0	-0.99	2	2
mol:Oxysterols	0.003	0.006	-10000	0	-10000	0	0
cholesterol transport	0.016	0.086	-10000	0	-0.45	2	2
PPARA	0.011	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.002	0.059	-10000	0	-0.41	11	11
RXRs/NUR77/BCL2	-0.039	0.13	-10000	0	-0.25	128	128
SREBF1	0.022	0.08	-10000	0	-0.5	1	1
RXRs/RXRs/DNA/9cRA	0	0.085	0.27	1	-0.21	71	72
ABCA1	0.022	0.08	-10000	0	-0.5	1	1
RARs/THRs	-0.021	0.099	-10000	0	-0.19	129	129
RXRs/FXR	-0.007	0.091	-10000	0	-0.22	73	73
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.011	0	-9999	-10000	0	0
EGFR	0	0.066	-9999	-0.4	14	14
EGF/EGFR	-0.067	0.099	-9999	-0.2	175	175
EGF/EGFR dimer/SHC/GRB2/SOS1	0.019	0.049	-9999	-0.34	1	1
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.12	0.19	-9999	-0.41	163	163
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.006	0.073	-9999	-0.34	25	25
EGF/EGFR dimer/SHC	0.006	0.058	-9999	-0.24	16	16
mol:GDP	-0.011	0.041	-9999	-0.33	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.006	0.047	-9999	-0.41	7	7
GRB2/SOS1	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.01	0.036	-9999	-0.3	1	1
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	-0.01	0.037	-9999	-0.31	1	1
FRAP1	0.015	0.046	-9999	-0.32	1	1
EGF/EGFR dimer	-0.003	0.069	-9999	-0.25	38	38
SOS1	0.011	0	-9999	-10000	0	0
GRB2	0.011	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.076	0.14	-9999	-0.28	167	167

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.009	0.031	-9999	-0.41	3	3
SVIL	-0.036	0.13	-9999	-0.41	61	61
ZNF318	0.01	0.005	-9999	-10000	0	0
JMJD2C	-0.004	0.031	-9999	-0.11	38	38
T-DHT/AR/Ubc9	-0.026	0.1	-9999	-0.24	93	93
CARM1	0.011	0	-9999	-10000	0	0
PRDX1	0.011	0	-9999	-10000	0	0
PELP1	0.011	0.001	-9999	-10000	0	0
CTNNB1	0.011	0.002	-9999	-10000	0	0
AKT1	0.011	0.001	-9999	-10000	0	0
PTK2B	0.011	0.002	-9999	-10000	0	0
MED1	0.011	0.002	-9999	-10000	0	0
MAK	-0.014	0.087	-9999	-0.33	38	38
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.007	0.04	-9999	-0.41	5	5
GSN	0.007	0.044	-9999	-0.41	6	6
NCOA2	-0.004	0.077	-9999	-0.41	19	19
NCOA6	0.011	0.002	-9999	-10000	0	0
DNA-PK	0.022	0.005	-9999	-10000	0	0
NCOA4	0.011	0	-9999	-10000	0	0
PIAS3	0.011	0.002	-9999	-10000	0	0
cell proliferation	-0.013	0.024	-9999	-10000	0	0
XRCC5	0.011	0.001	-9999	-10000	0	0
UBE3A	0.012	0.002	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.047	0.12	-9999	-0.25	131	131
FHL2	0.001	0.11	-9999	-0.98	5	5
RANBP9	0.011	0.002	-9999	-10000	0	0
JMJD1A	0.005	0.03	-9999	-0.13	23	23
CDK6	0.001	0.064	-9999	-0.41	13	13
TGFB1I1	-0.12	0.2	-9999	-0.41	176	176
T-DHT/AR/CyclinD1	-0.026	0.11	-9999	-0.24	95	95
XRCC6	0.011	0.001	-9999	-10000	0	0
T-DHT/AR	-0.021	0.12	-9999	-0.26	100	100
CTDSP1	0.011	0.001	-9999	-10000	0	0
CTDSP2	0.01	0.003	-9999	-10000	0	0
BRCA1	0.011	0.002	-9999	-10000	0	0
TCF4	-0.005	0.079	-9999	-0.41	20	20
CDKN2A	-0.13	0.17	-9999	-0.33	228	228
SRF	0.016	0.011	-9999	-10000	0	0
NKX3-1	-0.023	0.17	-9999	-0.84	19	19
KLK3	-0.006	0.044	-9999	-10000	0	0
TMF1	0.011	0.001	-9999	-10000	0	0
HNRNPA1	0.011	0.002	-9999	-10000	0	0
AOF2	0	0.002	-9999	-10000	0	0
APPL1	0.018	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.026	0.1	-9999	-0.24	93	93
AR	-0.062	0.16	-9999	-0.42	93	93
UBA3	0.011	0.001	-9999	-10000	0	0
PATZ1	0.011	0.002	-9999	-10000	0	0
PAWR	0.011	0.001	-9999	-10000	0	0
PRKDC	0.011	0.001	-9999	-10000	0	0
PA2G4	0.011	0.002	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.022	0.094	-9999	-0.22	93	93
RPS6KA3	0.011	0.018	-9999	-0.41	1	1
T-DHT/AR/ARA70	-0.026	0.1	-9999	-0.24	95	95
LATS2	0.01	0.018	-9999	-0.41	1	1
T-DHT/AR/PRX1	-0.022	0.094	-9999	-0.22	93	93
Cyclin D3/CDK11 p58	0.008	0	-9999	-10000	0	0
VAV3	-0.068	0.14	-9999	-0.33	127	127
KLK2	-0.067	0.2	-9999	-0.87	29	29
CASP8	0.011	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.023	0.11	-9999	-0.23	106	106
TMPRSS2	-0.018	0.14	-9999	-0.88	10	10
CCND1	0.009	0.025	-9999	-0.33	3	3
PIAS1	0.012	0.002	-9999	-10000	0	0
mol:T-DHT	-0.001	0.02	-9999	-0.066	36	36
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.012	0.004	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.032	0.11	-9999	-0.25	107	107
CMTM2	0.009	0.025	-9999	-0.33	3	3
SNURF	-0.024	0.11	-9999	-0.41	42	42
ZMIZ1	0.008	0.037	-9999	-0.42	3	3
CCND3	0.011	0	-9999	-10000	0	0
TGIF1	0.011	0.002	-9999	-10000	0	0
FKBP4	0.011	0.002	-9999	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.004	0.056	-9999	-0.2	37	37
RGS9BP	-0.005	0.07	-9999	-0.33	24	24
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.015	-9999	-0.33	1	1
mol:Na +	-0.005	0.054	-9999	-0.23	30	30
mol:ADP	0.007	0.015	-9999	-0.22	2	2
GNAT2	0.007	0.025	-9999	-0.33	3	3
RGS9-1/Gbeta5/R9AP	-0.041	0.11	-9999	-0.22	139	139
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.007	0.015	-9999	-0.19	3	3
GRK7	0.006	0.015	-9999	-0.33	1	1
CNGB3	-0.014	0.089	-9999	-0.41	26	26
Cone Metarhodopsin II/X-Arrestin	0.002	0.01	-9999	-0.22	1	1
mol:Ca2+	-0.002	0.05	-9999	-0.2	31	31
Cone PDE6	-0.031	0.092	-9999	-0.19	118	118
Cone Metarhodopsin II	0.006	0.011	-9999	-0.16	2	2
Na + (4 Units)	-0.002	0.05	-9999	-0.2	31	31
GNAT2/GDP	-0.03	0.093	-9999	-0.19	118	118
GNB5	0.011	0	-9999	-10000	0	0
mol:GMP (4 units)	0.008	0.016	-9999	-0.16	4	4
Cone Transducin	0.004	0.06	-9999	-0.21	37	37
SLC24A2	0.004	0.015	-9999	-0.33	1	1
GNB3/GNGT2	-0.003	0.075	-9999	-0.29	35	35
GNB3	-0.015	0.1	-9999	-0.41	33	33
GNAT2/GTP	0.006	0.017	-9999	-0.22	3	3
CNGA3	0.004	0.029	-9999	-0.33	4	4
ARR3	0.003	0.015	-9999	-0.33	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.005	0.055	-9999	-0.23	30	30
mol:Pi	-0.041	0.11	-9999	-0.22	139	139
Cone CNG Channel	-0.011	0.042	-9999	-0.18	26	26
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.004	0.015	-9999	-0.33	1	1
RGS9	-0.08	0.17	-9999	-0.41	118	118
PDE6C	0.003	0.015	-9999	-0.33	1	1
GNGT2	0.009	0.031	-9999	-0.41	3	3
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.004	-9999	-10000	0	0

×

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

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
MET/RANBP9	0.012	0.034	-10000	0	-0.25	9	9
CRKL	-0.014	0.096	-10000	0	-0.39	11	11
mol:PIP3	-0.009	0.042	0.38	6	-10000	0	6
AKT1	0.005	0.03	0.28	6	-10000	0	6
PTK2B	0.011	0	-10000	0	-10000	0	0
RAPGEF1	-0.008	0.092	-10000	0	-0.41	9	9
RANBP10	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
HGF/MET/SHIP2	-0.033	0.11	-10000	0	-0.23	115	115
MAP3K5	0	0.09	-10000	0	-0.39	10	10
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.022	0.096	-10000	0	-0.2	114	114
AP1	-0.068	0.12	-10000	0	-0.25	168	168
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.21	0.34	-10000	0	-0.72	168	168
STAT3 (dimer)	-0.016	0.097	-10000	0	-0.4	5	5
GAB1/CRKL/SHP2/PI3K	-0.034	0.076	-10000	0	-0.4	11	11
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
CBL/CRK	-0.007	0.092	-10000	0	-0.46	7	7
PTPN11	0.011	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.011	0	-10000	0	-10000	0	0
PTEN	0.006	0.044	-10000	0	-0.41	6	6
ELK1	-0.003	0.019	-10000	0	-0.15	5	5
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.026	0.052	-10000	0	-0.26	5	5
PAK1	0.01	0.028	0.27	6	-10000	0	6
HGF/MET/RANBP10	-0.033	0.11	-10000	0	-0.23	115	115
HRAS	-0.026	0.12	-10000	0	-0.55	7	7
DOCK1	-0.01	0.097	-10000	0	-0.43	11	11
GAB1	-0.021	0.1	-10000	0	-0.42	11	11
CRK	-0.014	0.096	-10000	0	-0.43	9	9
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.088	0.17	-10000	0	-0.42	114	114
JUN	0.006	0.047	-10000	0	-0.41	7	7
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.026	0.075	-10000	0	-0.17	114	114
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
cell morphogenesis	-0.001	0.11	-10000	0	-0.4	10	10
GRB2/SHC	-0.01	0.067	-10000	0	-0.27	5	5
FOS	-0.12	0.19	-10000	0	-0.41	167	167
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.003	0.019	-10000	0	-0.15	5	5
HGF/MET/MUC20	-0.04	0.11	-10000	0	-0.24	118	118
cell migration	-0.01	0.067	-10000	0	-0.27	5	5
GRB2	0.011	0	-10000	0	-10000	0	0
CBL	0.011	0	-10000	0	-10000	0	0
MET/RANBP10	0.012	0.034	-10000	0	-0.25	9	9
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.02	0.096	-10000	0	-0.2	117	117
MET/MUC20	0.004	0.034	-10000	0	-0.26	9	9
RAP1B	-0.002	0.087	-10000	0	-0.43	7	7
RAP1A	-0.002	0.087	-10000	0	-0.43	7	7
HGF/MET/RANBP9	-0.033	0.11	-10000	0	-0.23	115	115
RAF1	-0.019	0.11	-10000	0	-0.6	5	5
STAT3	-0.016	0.098	-10000	0	-0.4	5	5
cell proliferation	-0.025	0.13	-10000	0	-0.28	114	114
RPS6KB1	-0.003	0.029	-10000	0	-0.14	3	3
MAPK3	-0.007	0.018	-10000	0	-10000	0	0
MAPK1	-0.007	0.018	-10000	0	-10000	0	0
RANBP9	0.011	0	-10000	0	-10000	0	0
MAPK8	0.01	0.096	-10000	0	-0.41	13	13
SRC	-0.012	0.091	-10000	0	-0.37	5	5
PI3K	-0.012	0.073	-10000	0	-0.29	10	10
MET/Glomulin	0.006	0.03	-10000	0	-0.22	9	9
SOS1	0.011	0	-10000	0	-10000	0	0
MAP2K1	-0.012	0.11	-10000	0	-0.55	5	5
MET	0.005	0.049	-10000	0	-0.37	9	9
MAP4K1	-0.006	0.092	-10000	0	-0.46	7	7
PTK2	0.011	0	-10000	0	-10000	0	0
MAP2K2	-0.012	0.11	-10000	0	-0.55	5	5
BAD	0.01	0.028	0.27	6	-10000	0	6
MAP2K4	0.006	0.084	-10000	0	-0.36	10	10
SHP2/GRB2/SOS1/GAB1	-0.034	0.076	-10000	0	-0.42	9	9
INPPL1	0.011	0	-10000	0	-10000	0	0
PXN	0.011	0	-10000	0	-10000	0	0
SH3KBP1	0.011	0	-10000	0	-10000	0	0
HGS	-0.018	0.07	-10000	0	-0.15	114	114
PLCgamma1/PKC	0.008	0	-10000	0	-10000	0	0
HGF	-0.076	0.17	-10000	0	-0.41	112	112
RASA1	0.007	0.04	-10000	0	-0.41	5	5
NCK1	0.009	0.025	-10000	0	-0.41	2	2
PTPRJ	0.011	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.013	0.076	-10000	0	-0.27	7	7
PDPK1	-0.002	0.034	0.31	6	-10000	0	6
HGF/MET/SHIP	-0.033	0.11	-10000	0	-0.23	119	119

×

BCR signaling 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
JUN	0.015	0.085	-10000	0	-0.29	31	31
IKBKB	0.027	0.048	0.16	1	-0.17	3	4
AKT1	0.005	0.065	0.19	4	-0.2	28	32
IKBKG	0.029	0.049	0.16	1	-0.18	3	4
CALM1	0.02	0.079	0.17	67	-0.25	20	87
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
MAP3K1	0.005	0.11	-10000	0	-0.43	26	26
MAP3K7	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0.015	0.082	0.18	67	-0.26	21	88
DOK1	0.011	0	-10000	0	-10000	0	0
AP-1	0	0.076	0.14	40	-0.19	30	70
LYN	0.011	0	-10000	0	-10000	0	0
BLNK	0.009	0.029	-10000	0	-0.38	3	3
SHC1	0.011	0	-10000	0	-10000	0	0
BCR complex	-0.023	0.096	-10000	0	-0.24	83	83
CD22	-0.059	0.13	-10000	0	-0.5	32	32
CAMK2G	0.025	0.075	0.17	67	-0.23	20	87
CSNK2A1	0.011	0	-10000	0	-10000	0	0
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
SHC/GRB2/SOS1	-0.019	0.047	-10000	0	-0.3	3	3
GO:0007205	0.015	0.083	0.18	67	-0.27	21	88
SYK	0.01	0.015	-10000	0	-0.33	1	1
ELK1	0.02	0.079	0.17	67	-0.25	20	87
NFATC1	0.004	0.1	0.18	3	-0.32	36	39
B-cell antigen/BCR complex	-0.023	0.096	-10000	0	-0.24	83	83
PAG1/CSK	0.015	0.022	-10000	0	-0.28	3	3
NFKBIB	0.019	0.021	0.083	1	-0.12	1	2
HRAS	0.02	0.071	0.19	1	-0.23	20	21
NFKBIA	0.019	0.021	0.083	1	-0.12	1	2
NF-kappa-B/RelA/I kappa B beta	0.022	0.02	0.084	1	-0.14	1	2
RasGAP/Csk	0.001	0.073	-10000	0	-0.2	35	35
mol:GDP	0.014	0.079	0.17	67	-0.25	21	88
PTEN	0.006	0.044	-10000	0	-0.41	6	6
CD79B	-0.008	0.088	-10000	0	-0.41	25	25
NF-kappa-B/RelA/I kappa B alpha	0.022	0.02	0.084	1	-0.14	1	2
GRB2	0.011	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.009	0.12	-10000	0	-0.43	30	30
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
mol:IP3	0.015	0.084	0.18	67	-0.27	21	88
CSK	0.011	0	-10000	0	-10000	0	0
FOS	-0.031	0.12	0.17	45	-0.25	44	89
CHUK	0.029	0.049	0.16	1	-0.18	3	4
IBTK	0.011	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.013	0.047	-10000	0	-0.3	5	5
PTPN6	-0.032	0.13	-10000	0	-0.48	31	31
RELA	0.011	0	-10000	0	-10000	0	0
BCL2A1	0.019	0.016	-10000	0	-10000	0	0
VAV2	-0.008	0.11	-10000	0	-0.44	27	27
ubiquitin-dependent protein catabolic process	0.022	0.021	0.086	1	-0.12	1	2
BTK	-0.005	0.065	0.27	1	-1.1	2	3
CD19	-0.04	0.11	-10000	0	-0.33	52	52
MAP4K1	0.003	0.052	-10000	0	-0.33	13	13
CD72	0.009	0.025	-10000	0	-0.33	3	3
PAG1	0.009	0.031	-10000	0	-0.41	3	3
MAPK14	0.012	0.096	-10000	0	-0.37	26	26
SH3BP5	-0.05	0.15	-10000	0	-0.41	79	79
PIK3AP1	0.022	0.092	0.2	64	-0.3	20	84
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.014	0.054	-10000	0	-0.34	5	5
RAF1	0.025	0.068	0.19	1	-0.22	19	20
RasGAP/p62DOK/SHIP	-0.024	0.058	-10000	0	-0.34	4	4
CD79A	-0.027	0.11	-10000	0	-0.34	60	60
re-entry into mitotic cell cycle	0	0.076	0.14	40	-0.19	30	70
RASA1	0.007	0.04	-10000	0	-0.41	5	5
MAPK3	0.034	0.061	0.18	1	-0.26	3	4
MAPK1	0.034	0.061	0.18	1	-0.26	3	4
CD72/SHP1	-0.025	0.13	-10000	0	-0.45	31	31
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	0.01	0.099	-10000	0	-0.36	30	30
actin cytoskeleton organization	0	0.1	-10000	0	-0.39	26	26
NF-kappa-B/RelA	0.047	0.038	0.16	1	-0.18	1	2
Calcineurin	-0.011	0.045	-10000	0	-0.31	5	5
PI3K	-0.046	0.093	-10000	0	-0.36	32	32
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.019	0.094	0.2	66	-0.31	21	87
SOS1	0.011	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.023	0.17	-10000	0	-0.64	34	34
DAPP1	-0.049	0.18	-10000	0	-0.72	34	34
cytokine secretion	0.005	0.096	0.18	3	-0.3	36	39
mol:DAG	0.015	0.084	0.18	67	-0.27	21	88
PLCG2	0.01	0.023	-10000	0	-0.37	2	2
MAP2K1	0.03	0.065	0.19	1	-0.29	3	4
B-cell antigen/BCR complex/FcgammaRIIB	-0.013	0.084	-10000	0	-0.2	85	85
mol:PI-3-4-5-P3	-0.033	0.073	0.21	5	-0.26	32	37
ETS1	0.029	0.072	0.17	67	-0.21	20	87
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.003	0.07	-10000	0	-0.2	30	30
B-cell antigen/BCR complex/LYN	-0.033	0.1	-10000	0	-0.45	28	28
MALT1	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	-0.001	0.11	-10000	0	-0.41	26	26
B-cell antigen/BCR complex/LYN/SYK	-0.054	0.12	-10000	0	-0.48	28	28
CARD11	0.016	0.085	0.17	65	-0.26	21	86
FCGR2B	0.008	0.034	-10000	0	-0.39	4	4
PPP3CA	0.011	0	-10000	0	-10000	0	0
BCL10	0.011	0	-10000	0	-10000	0	0
IKK complex	0.02	0.024	0.11	1	-10000	0	1
PTPRC	0.003	0.058	-10000	0	-0.4	11	11
PDPK1	-0.001	0.062	0.17	4	-0.18	29	33
PPP3CB	0.011	0	-10000	0	-10000	0	0
PPP3CC	0.008	0.036	-10000	0	-0.41	4	4
POU2F2	0.02	0.015	-10000	0	-0.1	1	1

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.014	0.043	-9999	-0.41	5	5
Syndecan-4/Syndesmos	-0.012	0.069	-9999	-10000	0	0
positive regulation of JNK cascade	-0.12	0.11	-9999	-0.35	37	37
Syndecan-4/ADAM12	-0.015	0.072	-9999	-10000	0	0
CCL5	0.003	0.053	-9999	-0.37	11	11
Rac1/GDP	0.008	0	-9999	-10000	0	0
DNM2	0.011	0	-9999	-10000	0	0
ITGA5	0.011	0	-9999	-10000	0	0
SDCBP	0.011	0	-9999	-10000	0	0
PLG	-0.028	0.12	-9999	-0.38	55	55
ADAM12	0.003	0.05	-9999	-0.33	12	12
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.039	0.042	-9999	-0.14	1	1
Syndecan-4/Laminin alpha1	-0.062	0.096	-9999	-0.34	18	18
Syndecan-4/CXCL12/CXCR4	-0.12	0.11	-9999	-0.37	37	37
Syndecan-4/Laminin alpha3	-0.017	0.075	-9999	-10000	0	0
MDK	0.01	0.015	-9999	-0.33	1	1
Syndecan-4/FZD7	-0.042	0.099	-9999	-0.35	11	11
Syndecan-4/Midkine	-0.012	0.07	-9999	-10000	0	0
FZD7	-0.055	0.15	-9999	-0.41	85	85
Syndecan-4/FGFR1/FGF	-0.11	0.1	-9999	-0.36	33	33
THBS1	-0.046	0.14	-9999	-0.41	74	74
integrin-mediated signaling pathway	-0.016	0.074	-9999	-0.37	2	2
positive regulation of MAPKKK cascade	-0.12	0.11	-9999	-0.35	37	37
Syndecan-4/TACI	-0.018	0.076	-9999	-0.34	2	2
CXCR4	0.011	0	-9999	-10000	0	0
cell adhesion	0.013	0.051	-9999	-0.26	5	5
Syndecan-4/Dynamin	-0.012	0.069	-9999	-10000	0	0
Syndecan-4/TSP1	-0.038	0.095	-9999	-0.37	9	9
Syndecan-4/GIPC	-0.012	0.069	-9999	-10000	0	0
Syndecan-4/RANTES	-0.015	0.074	-9999	-0.36	2	2
ITGB1	0.011	0	-9999	-10000	0	0
LAMA1	-0.1	0.16	-9999	-0.33	183	183
LAMA3	-0.001	0.069	-9999	-0.41	15	15
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	-0.007	0.1	-9999	-0.37	36	36
Syndecan-4/alpha-Actinin	-0.012	0.069	-9999	-10000	0	0
TFPI	-0.039	0.14	-9999	-0.41	64	64
F2	-0.024	0.095	-9999	-0.33	48	48
alpha5/beta1 Integrin	0.016	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.06	0.097	-9999	-0.32	22	22
ACTN1	0.011	0	-9999	-10000	0	0
TNC	0	0.066	-9999	-0.4	14	14
Syndecan-4/CXCL12	-0.13	0.12	-9999	-0.38	37	37
FGF6	0	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CXCL12	-0.26	0.2	-9999	-0.41	345	345
TNFRSF13B	-0.002	0.059	-9999	-0.33	17	17
FGF2	-0.22	0.21	-9999	-0.41	295	295
FGFR1	0.01	0.018	-9999	-0.41	1	1
Syndecan-4/PI-4-5-P2	-0.018	0.069	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.011	0.039	-9999	-0.39	5	5
cell migration	-0.017	0.019	-9999	-10000	0	0
PRKCD	0.015	0.008	-9999	-10000	0	0
vasculogenesis	-0.037	0.092	-9999	-0.36	9	9
SDC4	-0.019	0.072	-9999	-10000	0	0
Syndecan-4/Tenascin C	-0.017	0.076	-9999	-0.38	2	2
Syndecan-4/PI-4-5-P2/PKC alpha	-0.031	0.034	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.012	0.069	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	222	222
Rac1/GTP	0.013	0.052	-9999	-0.26	5	5
cytoskeleton organization	-0.011	0.068	-9999	-10000	0	0
GIPC1	0.011	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.034	0.097	-9999	-0.36	13	13

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.011	0	-9999	-10000	0	0
GNAT1/GTP	0.002	0.024	-9999	-0.22	6	6
Metarhodopsin II/Arrestin	0.006	0.015	-9999	-0.18	3	3
PDE6G/GNAT1/GTP	-0.008	0.059	-9999	-0.18	53	53
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.002	0.035	-9999	-0.33	6	6
GRK1	0.002	0.015	-9999	-0.33	1	1
CNG Channel	-0.03	0.064	-9999	-0.28	14	14
mol:Na +	-0.019	0.054	-9999	-0.34	6	6
mol:ADP	0.002	0.015	-9999	-0.33	1	1
RGS9-1/Gbeta5/R9AP	-0.041	0.11	-9999	-0.22	139	139
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.019	0.055	-9999	-0.34	6	6
CNGB1	-0.008	0.076	-9999	-0.33	29	29
RDH5	0.009	0.025	-9999	-0.33	3	3
SAG	0.005	0.005	-9999	-10000	0	0
mol:Ca2+	0.01	0.061	-9999	-0.32	6	6
Na + (4 Units)	-0.017	0.049	-9999	-0.31	6	6
RGS9	-0.08	0.17	-9999	-0.41	118	118
GNB1/GNGT1	-0.067	0.11	-9999	-0.22	193	193
GNAT1/GDP	-0.032	0.093	-9999	-0.2	119	119
GUCY2D	0	0.052	-9999	-0.33	13	13
GNGT1	-0.11	0.16	-9999	-0.33	193	193
GUCY2F	0.005	0.005	-9999	-10000	0	0
GNB5	0.011	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.003	0.066	-9999	-0.21	23	23
mol:11-cis-retinal	0.009	0.025	-9999	-0.33	3	3
mol:cGMP	0.007	0.046	-9999	-0.25	4	4
GNB1	0.011	0	-9999	-10000	0	0
Rhodopsin	0.009	0.024	-9999	-0.22	6	6
SLC24A1	0.011	0	-9999	-10000	0	0
CNGA1	0.001	0.056	-9999	-0.33	15	15
Metarhodopsin II	0.004	0.015	-9999	-0.16	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.004	0.049	-9999	-0.23	10	10
RGS9BP	-0.005	0.07	-9999	-0.33	24	24
Metarhodopsin II/Transducin	-0.014	0.038	-9999	-10000	0	0
GCAP Family/Ca ++	0.003	0.04	-9999	-0.21	8	8
PDE6A/B	0.002	0.062	-9999	-0.26	28	28
mol:Pi	-0.041	0.11	-9999	-0.22	139	139
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.046	0.087	-9999	-0.17	78	78
PDE6B	-0.007	0.085	-9999	-0.4	24	24
PDE6A	0.008	0.029	-9999	-0.33	4	4
PDE6G	-0.019	0.097	-9999	-0.33	48	48
RHO	0.003	0.025	-9999	-0.33	3	3
PDE6	-0.061	0.089	-9999	-0.33	21	21
GUCA1A	-0.003	0.059	-9999	-0.33	17	17
GC2/GCAP Family	0.006	0.04	-9999	-0.21	8	8
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.005	0.051	-9999	-0.41	8	8

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.008	0.045	-9999	-0.24	15	15
NFATC2	-0.011	0.079	-9999	-0.24	55	55
NFATC3	0.015	0.018	-9999	-10000	0	0
CD40LG	-0.056	0.18	-9999	-0.47	50	50
PTGS2	-0.076	0.21	-9999	-0.49	78	78
JUNB	0.007	0.04	-9999	-0.41	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.007	-9999	-10000	0	0
CaM/Ca2+	-0.001	0.007	-9999	-10000	0	0
CALM1	0.011	0.005	-9999	-10000	0	0
JUN	0.006	0.048	-9999	-0.41	7	7
mol:Ca2+	-0.002	0.007	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.004	-9999	-10000	0	0
FOSL1	-0.015	0.091	-9999	-0.33	42	42
CREM	0.011	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.036	0.082	-9999	-0.3	29	29
FOS	-0.12	0.2	-9999	-0.41	167	167
IFNG	-0.067	0.19	-9999	-0.48	60	60
AP-1/NFAT1-c-4	-0.064	0.2	-9999	-0.49	57	57
FASLG	-0.055	0.18	-9999	-0.5	41	41
NFAT1-c-4/ICER1	-0.011	0.082	-9999	-0.27	25	25
IL2RA	-0.056	0.18	-9999	-0.5	42	42
FKBP12/FK506	0.008	0	-9999	-10000	0	0
CSF2	-0.056	0.18	-9999	-0.47	42	42
JunB/Fra1/NFAT1-c-4	-0.022	0.085	-9999	-0.26	31	31
IL4	-0.056	0.17	-9999	-0.48	38	38
IL2	-0.009	0.03	-9999	-10000	0	0
IL3	-0.011	0.015	-9999	-10000	0	0
FKBP1A	0.011	0	-9999	-10000	0	0
BATF3	0.01	0.015	-9999	-0.33	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.011	0	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.039	0.12	-9999	-0.28	102	102
AKT1	0.02	0.15	-9999	-0.51	35	35
PTK2B	-0.022	0.15	-9999	-0.54	33	33
VEGFR2 homodimer/Frs2	-0.006	0.14	-9999	-0.56	33	33
CAV1	-0.062	0.16	-9999	-0.41	94	94
CALM1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.004	0.13	-9999	-0.52	33	33
endothelial cell proliferation	0.017	0.15	-9999	-0.45	42	42
mol:Ca2+	-0.002	0.15	-9999	-0.55	33	33
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.011	0.13	-9999	-0.49	33	33
RP11-342D11.1	-0.009	0.15	-9999	-0.56	33	33
CDH5	0.006	0.047	-9999	-0.41	7	7
VEGFA homodimer	0.029	0.01	-9999	-0.2	1	1
SHC1	0.011	0	-9999	-10000	0	0
SHC2	-0.049	0.15	-9999	-0.41	77	77
HRAS/GDP	-0.035	0.12	-9999	-0.47	33	33
SH2D2A	-0.002	0.065	-9999	-0.33	21	21
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.035	0.12	-9999	-0.47	33	33
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.003	0.14	-9999	-0.53	33	33
VEGFR1 homodimer	0.011	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.039	0.13	-9999	-0.52	33	33
GRB10	-0.002	0.15	-9999	-0.56	33	33
PTPN11	0.011	0	-9999	-10000	0	0
GRB2	0.011	0	-9999	-10000	0	0
PAK1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.013	0.13	-9999	-0.5	33	33
HRAS	0.011	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.014	0.12	-9999	-0.38	33	33
HIF1A	0.011	0	-9999	-10000	0	0
FRS2	0.011	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.009	0.12	-9999	-0.48	33	33
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.005	0.081	-9999	-0.41	21	21
Nck/Pak	0.015	0.018	-9999	-0.28	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.004	0.13	-9999	-0.52	33	33
mol:GDP	-0.038	0.12	-9999	-0.5	33	33
mol:NADP	0.023	0.12	-9999	-0.4	33	33
eNOS/Hsp90	0.028	0.11	-9999	-0.38	33	33
PIK3R1	0.007	0.04	-9999	-0.41	5	5
mol:IP3	-0.002	0.15	-9999	-0.56	33	33
HIF1A/ARNT	0.016	0	-9999	-10000	0	0
SHB	0.011	0	-9999	-10000	0	0
VEGFA	0.013	0.001	-9999	-10000	0	0
VEGFC	0.004	0.054	-9999	-0.41	9	9
FAK1/Vinculin	-0.01	0.16	-9999	-0.59	33	33
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.028	0.16	-9999	-0.58	33	33
PTPN6	0.01	0.015	-9999	-0.33	1	1
EPAS1	-0.001	0.084	-9999	-0.32	33	33
mol:L-citrulline	0.023	0.12	-9999	-0.4	33	33
ITGAV	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.011	0.13	-9999	-0.49	33	33
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.16	-9999	-0.6	33	33
VEGFR2/3 heterodimer	-0.016	0.15	-9999	-0.58	33	33
VEGFB	0.011	0	-9999	-10000	0	0
MAPK11	-0.004	0.16	-9999	-0.57	34	34
VEGFR2 homodimer	-0.012	0.16	-9999	-0.65	33	33
FLT1	0.011	0	-9999	-10000	0	0
NEDD4	-0.021	0.12	-9999	-0.41	44	44
MAPK3	-0.007	0.14	-9999	-0.47	41	41
MAPK1	-0.007	0.14	-9999	-0.47	41	41
VEGFA145/NRP2	0.004	0.062	-9999	-0.28	25	25
VEGFR1/2 heterodimer	-0.006	0.14	-9999	-0.56	33	33
KDR	-0.012	0.16	-9999	-0.65	33	33
VEGFA165/NRP1/VEGFR2 homodimer	-0.011	0.16	-9999	-0.56	35	35
SRC	0.011	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.006	0.15	-9999	-0.48	41	41
PI3K	0.01	0.16	-9999	-0.57	35	35
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.003	0.13	-9999	-0.52	33	33
FES	-0.003	0.15	-9999	-0.56	34	34
GAB1	-0.04	0.14	-9999	-0.6	33	33
VEGFR2 homodimer/VEGFA homodimer/Src	0.004	0.13	-9999	-0.52	33	33
CTNNB1	0.011	0	-9999	-10000	0	0
SOS1	0.011	0	-9999	-10000	0	0
ARNT	0.011	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.012	0.13	-9999	-0.42	42	42
VEGFR2 homodimer/VEGFA homodimer/Yes	0.004	0.13	-9999	-0.52	33	33
PI3K/GAB1	0.021	0.16	-9999	-0.53	35	35
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.014	0.12	-9999	-0.47	33	33
PRKACA	0.011	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.011	0.15	-9999	-0.56	33	33
HSP90AA1	0.011	0	-9999	-10000	0	0
CDC42	-0.003	0.15	-9999	-0.56	33	33
actin cytoskeleton reorganization	-0.003	0.14	-9999	-0.53	33	33
PTK2	-0.018	0.18	-9999	-0.64	33	33
EDG1	-0.009	0.15	-9999	-0.56	33	33
mol:DAG	-0.002	0.15	-9999	-0.56	33	33
CaM/Ca2+	0.003	0.14	-9999	-0.51	33	33
MAP2K3	0.002	0.15	-9999	-0.53	33	33
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.002	0.16	-9999	-0.58	33	33
PLCG1	-0.003	0.15	-9999	-0.56	33	33
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.011	0.13	-9999	-0.49	33	33
IQGAP1	0.011	0	-9999	-10000	0	0
YES1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.004	0.13	-9999	-0.52	33	33
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.003	0.13	-9999	-0.52	33	33
cell migration	0.012	0.15	-9999	-0.53	33	33
mol:PI-3-4-5-P3	0.012	0.15	-9999	-0.53	35	35
FYN	0.011	0	-9999	-10000	0	0
VEGFB/NRP1	-0.002	0.14	-9999	-0.52	33	33
mol:NO	0.023	0.12	-9999	-0.4	33	33
PXN	0.011	0	-9999	-10000	0	0
HRAS/GTP	-0.035	0.12	-9999	-0.47	33	33
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.002	0.16	-9999	-0.58	33	33
VHL	0.01	0.018	-9999	-0.41	1	1
ITGB3	-0.068	0.16	-9999	-0.41	102	102
NOS3	0.022	0.13	-9999	-0.46	33	33
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.028	0.15	-9999	-0.55	33	33
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	-0.009	0.16	-9999	-0.51	39	39
PRKCB	-0.008	0.15	-9999	-0.52	36	36
VCL	0.011	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.008	0.15	-9999	-0.56	33	33
VEGFR1/2 heterodimer/VEGFA homodimer	0.004	0.13	-9999	-0.52	33	33
VEGFA165/NRP2	0.004	0.062	-9999	-0.28	25	25
MAPKKK cascade	0.019	0.13	-9999	-0.47	33	33
NRP2	-0.008	0.088	-9999	-0.41	25	25
VEGFC homodimer	0.004	0.054	-9999	-0.41	9	9
NCK1	0.009	0.025	-9999	-0.41	2	2
ROCK1	0.011	0	-9999	-10000	0	0
FAK1/Paxillin	-0.01	0.16	-9999	-0.59	33	33
MAP3K13	-0.004	0.15	-9999	-0.57	33	33
PDPK1	0.019	0.14	-9999	-0.47	35	35

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0	-9999	-10000	0	0
HDAC2	0.011	0.001	-9999	-10000	0	0
GNB1/GNG2	0.015	0.041	-9999	-0.22	15	15
forebrain development	-0.068	0.2	-9999	-0.44	105	105
GNAO1	-0.1	0.18	-9999	-0.41	143	143
SMO/beta Arrestin2	0.015	0.029	-9999	-0.28	5	5
SMO	0.007	0.04	-9999	-0.41	5	5
ARRB2	0.011	0.003	-9999	-10000	0	0
GLI3/SPOP	-0.029	0.11	-9999	-0.46	4	4
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.011	0	-9999	-10000	0	0
GNAI2	0.011	0.002	-9999	-10000	0	0
SIN3/HDAC complex	0.028	0.002	-9999	-10000	0	0
GNAI1	0.005	0.051	-9999	-0.41	8	8
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.066	0.13	-9999	-0.44	33	33
SAP30	0.011	0.001	-9999	-10000	0	0
mol:GDP	0.007	0.04	-9999	-0.41	5	5
MIM/GLI2A	0.013	0.018	-9999	-10000	0	0
IFT88	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GLI2	-0.012	0.078	-9999	-10000	0	0
GLI3	-0.036	0.12	-9999	-0.22	150	150
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
SAP18	0.011	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.011	0	-9999	-10000	0	0
GNG2	0.003	0.056	-9999	-0.4	10	10
Gi family/GTP	-0.039	0.11	-9999	-0.21	147	147
SIN3B	0.011	0.001	-9999	-10000	0	0
SIN3A	0.011	0	-9999	-10000	0	0
GLI3/Su(fu)	-0.004	0.086	-9999	-0.39	3	3
GLI2/Su(fu)	0.004	0.07	-9999	-0.23	3	3
FOXA2	-0.1	0.3	-9999	-1.1	49	49
neural tube patterning	-0.068	0.2	-9999	-0.44	105	105
SPOP	0.011	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.025	0.016	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CSNK1G2	0.011	0	-9999	-10000	0	0
CSNK1G3	0.011	0	-9999	-10000	0	0
MTSS1	0.013	0.018	-9999	-10000	0	0
embryonic limb morphogenesis	-0.068	0.2	-9999	-0.44	105	105
SUFU	0.021	0.018	-9999	-10000	0	0
LGALS3	0.009	0.025	-9999	-0.41	2	2
catabolic process	-0.035	0.13	-9999	-0.28	76	76
GLI3A/CBP	-0.044	0.13	-9999	-0.31	104	104
KIF3A	0.01	0.018	-9999	-0.41	1	1
GLI1	-0.07	0.2	-9999	-0.45	105	105
RAB23	0.007	0.04	-9999	-0.41	5	5
CSNK1A1	0.011	0	-9999	-10000	0	0
IFT172	0.011	0	-9999	-10000	0	0
RBBP7	0.011	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.024	0.021	-9999	-0.19	2	2
GNAZ	-0.002	0.073	-9999	-0.41	17	17
RBBP4	0.009	0.031	-9999	-0.41	3	3
CSNK1G1	0.011	0	-9999	-10000	0	0
PIAS1	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GLI2/SPOP	-0.006	0.073	-9999	-10000	0	0
STK36	0.012	0.004	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.03	0.1	-9999	-0.36	18	18
PTCH1	-0.055	0.18	-9999	-0.52	36	36
MIM/GLI1	-0.075	0.24	-9999	-0.47	127	127
CREBBP	-0.044	0.13	-9999	-0.31	104	104
Su(fu)/SIN3/HDAC complex	0.039	0.016	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.1	0.19	-10000	0	-0.41	149	149
HRAS	0.011	0	-10000	0	-10000	0	0
EGFR	0	0.066	-10000	0	-0.4	14	14
AKT	-0.068	0.13	-10000	0	-0.28	109	109
FOXO3	0.011	0	-10000	0	-10000	0	0
AKT1	0.011	0	-10000	0	-10000	0	0
FOXO1	0.009	0.031	-10000	0	-0.41	3	3
AKT3	-0.15	0.2	-10000	0	-0.41	204	204
FOXO4	0.009	0.025	-10000	0	-0.41	2	2
MET	0.005	0.049	-10000	0	-0.37	9	9
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
PIK3CB	0.011	0	-10000	0	-10000	0	0
NRAS	0.011	0	-10000	0	-10000	0	0
PIK3CG	-0.001	0.07	-10000	0	-0.4	16	16
PIK3R3	0.01	0.015	-10000	0	-0.33	1	1
PIK3R2	0.011	0	-10000	0	-10000	0	0
NF1	0.009	0.025	-10000	0	-0.41	2	2
RAS	-0.022	0.073	0.18	1	-0.26	14	15
ERBB2	0.002	0.054	-10000	0	-0.33	14	14
proliferation/survival/translation	0.011	0.066	0.22	20	-10000	0	20
PI3K	-0.013	0.074	0.15	2	-0.21	27	29
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
KRAS	0.01	0.015	-10000	0	-0.33	1	1
FOXO	0.023	0.022	-10000	0	-10000	0	0
AKT2	0.011	0	-10000	0	-10000	0	0
PTEN	0.006	0.044	-10000	0	-0.41	6	6

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.011	0	-9999	-10000	0	0
VLDLR	0.009	0.025	-9999	-0.41	2	2
LRPAP1	0.011	0	-9999	-10000	0	0
NUDC	0.011	0	-9999	-10000	0	0
RELN/LRP8	-0.071	0.12	-9999	-0.23	202	202
CaM/Ca2+	0.008	0	-9999	-10000	0	0
KATNA1	0.011	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.058	0.11	-9999	-0.2	196	196
IQGAP1/CaM	0.016	0	-9999	-10000	0	0
DAB1	-0.001	0.052	-9999	-0.33	13	13
IQGAP1	0.011	0	-9999	-10000	0	0
PLA2G7	0.006	0.043	-9999	-0.4	6	6
CALM1	0.011	0	-9999	-10000	0	0
DYNLT1	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.014	0.022	-9999	-0.22	5	5
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.011	0	-9999	-10000	0	0
CDK5R1	0.01	0.015	-9999	-0.33	1	1
LIS1/Poliovirus Protein 3A	0.013	0	-9999	-10000	0	0
CDK5R2	-0.028	0.1	-9999	-0.33	57	57
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.077	0.12	-9999	-0.23	213	213
YWHAE	0.011	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.032	0.091	-9999	-0.22	18	18
MAP1B	-0.012	0.055	-9999	-0.25	27	27
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.039	0.097	-9999	-0.3	3	3
RELN	-0.14	0.2	-9999	-0.41	200	200
PAFAH/LIS1	0.019	0.025	-9999	-0.22	6	6
LIS1/CLIP170	0.022	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.039	0.054	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.05	0.1	-9999	-0.25	7	7
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.04	0.095	-9999	-0.24	18	18
LIS1/IQGAP1	0.022	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	0.005	0.043	-9999	-0.33	9	9
PAFAH1B2	0.01	0.018	-9999	-0.41	1	1
MAP1B/LIS1/Dynein heavy chain	0.012	0.037	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.027	0.088	-9999	-0.26	2	2
LRP8	0.008	0.032	-9999	-0.33	5	5
NDEL1/Katanin 60	-0.032	0.091	-9999	-0.22	18	18
P39/CDK5	-0.057	0.1	-9999	-0.31	19	19
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.022	0	-9999	-10000	0	0
CDK5	-0.048	0.1	-9999	-0.28	4	4
PPP2R5D	0.011	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.019	0	-9999	-10000	0	0
CSNK2A1	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.052	0.1	-9999	-0.34	2	2
RELN/VLDLR	-0.057	0.11	-9999	-0.2	195	195
CDC42	0	0	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.011	0.045	-9999	-0.23	19	19
EPHB2	0.009	0.025	-9999	-0.33	3	3
Syndecan-2/TACI	0.006	0.052	-9999	-0.2	30	30
LAMA1	-0.1	0.16	-9999	-0.33	183	183
Syndecan-2/alpha2 ITGB1	0.015	0.062	-9999	-0.2	38	38
HRAS	0.011	0	-9999	-10000	0	0
Syndecan-2/CASK	0.006	0.039	-9999	-0.23	14	14
ITGA5	0.011	0	-9999	-10000	0	0
BAX	0.023	0.042	-9999	-10000	0	0
EPB41	0.01	0.018	-9999	-0.41	1	1
positive regulation of cell-cell adhesion	0.012	0.035	-9999	-0.2	14	14
LAMA3	-0.001	0.069	-9999	-0.41	15	15
EZR	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.024	0.12	-9999	-0.41	45	45
Syndecan-2/MMP2	0.001	0.068	-9999	-0.24	39	39
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.009	0.045	-9999	-0.28	13	13
dendrite morphogenesis	0.013	0.041	-9999	-0.22	17	17
Syndecan-2/GM-CSF	0.008	0.046	-9999	-0.22	21	21
determination of left/right symmetry	0.008	0.047	-9999	-0.28	14	14
Syndecan-2/PKC delta	0.014	0.039	-9999	-0.23	14	14
GNB2L1	0.011	0	-9999	-10000	0	0
MAPK3	0.015	0.042	-9999	-0.21	14	14
MAPK1	0.015	0.042	-9999	-0.21	14	14
Syndecan-2/RACK1	0.019	0.033	-9999	-0.18	14	14
NF1	0.009	0.025	-9999	-0.41	2	2
FGFR/FGF/Syndecan-2	0.008	0.047	-9999	-0.28	14	14
ITGA2	0.001	0.064	-9999	-0.41	13	13
MAPK8	0.018	0.047	-9999	-0.22	20	20
Syndecan-2/alpha2/beta1 Integrin	-0.034	0.089	-9999	-0.22	30	30
Syndecan-2/Kininogen	0.001	0.055	-9999	-0.19	39	39
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.024	0.031	-9999	-0.17	14	14
Syndecan-2/CASK/Protein 4.1	0.012	0.036	-9999	-0.2	15	15
extracellular matrix organization	0.013	0.04	-9999	-0.23	15	15
actin cytoskeleton reorganization	0.011	0.045	-9999	-0.23	19	19
Syndecan-2/Caveolin-2/Ras	0.002	0.072	-9999	-0.21	57	57
Syndecan-2/Laminin alpha3	0.007	0.057	-9999	-0.24	28	28
Syndecan-2/RasGAP	0.022	0.037	-9999	-0.17	19	19
alpha5/beta1 Integrin	0.016	0	-9999	-10000	0	0
PRKCD	0.011	0	-9999	-10000	0	0
Syndecan-2 dimer	0.013	0.041	-9999	-0.22	17	17
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.028	0.036	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
SDCBP	0.011	0	-9999	-10000	0	0
TNFRSF13B	-0.002	0.059	-9999	-0.33	17	17
RASA1	0.007	0.04	-9999	-0.41	5	5
alpha2/beta1 Integrin	0.009	0.045	-9999	-0.28	13	13
Syndecan-2/Synbindin	0.014	0.039	-9999	-0.23	14	14
TGFB1	0.01	0.018	-9999	-0.41	1	1
CASP3	0.02	0.035	-9999	-0.2	14	14
FN1	0.007	0.04	-9999	-0.41	5	5
Syndecan-2/IL8	-0.042	0.093	-9999	-0.18	171	171
SDC2	0.008	0.047	-9999	-0.28	14	14
KNG1	-0.01	0.07	-9999	-0.33	25	25
Syndecan-2/Neurofibromin	0.013	0.042	-9999	-0.23	16	16
TRAPPC4	0.011	0	-9999	-10000	0	0
CSF2	0.001	0.041	-9999	-0.33	8	8
Syndecan-2/TGFB1	0.013	0.04	-9999	-0.23	15	15
Syndecan-2/Syntenin/PI-4-5-P2	0.013	0.035	-9999	-0.2	14	14
Syndecan-2/Ezrin	0.02	0.035	-9999	-0.2	14	14
PRKACA	0.019	0.038	-9999	-0.2	16	16
angiogenesis	-0.042	0.093	-9999	-0.18	171	171
MMP2	-0.01	0.091	-9999	-0.41	27	27
IL8	-0.088	0.15	-9999	-0.33	158	158
calcineurin-NFAT signaling pathway	0.006	0.052	-9999	-0.2	30	30

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.01	0.039	-10000	0	-10000	0	0
SMARCC2	0.012	0.002	-10000	0	-10000	0	0
SMARCC1	0.012	0.003	-10000	0	-10000	0	0
TBX21	0.006	0.12	-10000	0	-0.67	10	10
SUMO2	0.01	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0.02	-10000	0	-0.32	2	2
FKBP4	0.011	0	-10000	0	-10000	0	0
FKBP5	0.005	0.051	-10000	0	-0.41	8	8
GR alpha/HSP90/FKBP51/HSP90	0.001	0.1	0.21	12	-0.25	54	66
PRL	-0.029	0.25	-10000	0	-1.2	20	20
cortisol/GR alpha (dimer)/TIF2	0.027	0.16	0.44	20	-0.43	8	28
RELA	-0.015	0.062	-10000	0	-0.22	10	10
FGG	0.005	0.14	0.37	14	-0.45	5	19
GR beta/TIF2	-0.015	0.13	0.23	12	-0.31	66	78
IFNG	-0.094	0.14	-10000	0	-0.51	10	10
apoptosis	-0.078	0.19	0.47	8	-0.59	28	36
CREB1	0.009	0.022	-10000	0	-10000	0	0
histone acetylation	0.038	0.074	0.23	13	-0.24	9	22
BGLAP	0.024	0.064	-10000	0	-10000	0	0
GR/PKAc	0.005	0.092	0.21	8	-0.24	34	42
NF kappa B1 p50/RelA	-0.024	0.11	-10000	0	-0.33	28	28
SMARCD1	0.012	0.003	-10000	0	-10000	0	0
MDM2	0.022	0.041	0.18	15	-10000	0	15
GATA3	0.002	0.069	-10000	0	-0.35	20	20
AKT1	0.005	0.002	-10000	0	-10000	0	0
CSF2	0.018	0.066	-10000	0	-10000	0	0
GSK3B	0.01	0.005	-10000	0	-10000	0	0
NR1I3	-0.055	0.17	0.46	7	-0.54	23	30
CSN2	0.003	0.11	0.31	11	-0.37	4	15
BRG1/BAF155/BAF170/BAF60A	0.035	0.009	-10000	0	-10000	0	0
NFATC1	0.002	0.069	-10000	0	-0.41	15	15
POU2F1	0.007	0.044	-10000	0	-0.23	17	17
CDKN1A	0.032	0.06	-10000	0	-1.3	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	-0.24	0.15	-10000	0	-0.33	401	401
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.1	0.14	0.22	15	-0.34	75	90
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.11	0.29	0.44	7	-0.81	71	78
JUN	-0.041	0.1	-10000	0	-0.36	16	16
IL4	0.007	0.08	-10000	0	-0.46	2	2
CDK5R1	0.01	0.015	-10000	0	-0.33	1	1
PRKACA	0.011	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.17	-10000	0	-0.36	194	194
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.009	0.095	0.21	11	-0.24	38	49
cortisol/GR alpha (monomer)	0.029	0.18	0.5	21	-0.47	4	25
NCOA2	-0.004	0.077	-10000	0	-0.41	19	19
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.15	0.2	-10000	0	-0.44	167	167
AP-1/NFAT1-c-4	-0.16	0.18	-10000	0	-0.48	67	67
AFP	-0.016	0.08	-10000	0	-0.42	1	1
SUV420H1	0.011	0	-10000	0	-10000	0	0
IRF1	0.026	0.088	0.33	1	-10000	0	1
TP53	0.027	0.027	-10000	0	-0.42	2	2
PPP5C	0.011	0	-10000	0	-10000	0	0
KRT17	-0.12	0.18	-10000	0	-0.77	16	16
KRT14	-0.052	0.11	0.43	1	-10000	0	1
TBP	0.019	0	-10000	0	-10000	0	0
CREBBP	0.031	0.046	-10000	0	-0.32	4	4
HDAC1	0.01	0.002	-10000	0	-10000	0	0
HDAC2	0.01	0.002	-10000	0	-10000	0	0
AP-1	-0.16	0.18	-10000	0	-0.48	67	67
MAPK14	0.01	0.005	-10000	0	-10000	0	0
MAPK10	-0.08	0.17	-10000	0	-0.41	116	116
MAPK11	0.008	0.026	-10000	0	-0.41	2	2
KRT5	-0.14	0.22	-10000	0	-0.63	46	46
interleukin-1 receptor activity	-0.001	0.002	-10000	0	-10000	0	0
NCOA1	0.012	0.018	-10000	0	-0.41	1	1
STAT1	0.016	0.021	-10000	0	-0.32	2	2
CGA	0.006	0.082	-10000	0	-0.36	3	3
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.009	0.097	0.29	3	-0.48	2	5
MAPK3	0.01	0.006	-10000	0	-10000	0	0
MAPK1	0.01	0.005	-10000	0	-10000	0	0
ICAM1	-0.015	0.11	-10000	0	-0.4	9	9
NFKB1	-0.016	0.064	-10000	0	-0.25	8	8
MAPK8	-0.017	0.097	0.26	1	-0.3	20	21
MAPK9	0.01	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.085	0.2	0.47	8	-0.61	29	37
BAX	0.034	0.025	-10000	0	-10000	0	0
POMC	-0.019	0.21	-10000	0	-1.3	10	10
EP300	0.032	0.037	-10000	0	-0.23	2	2
cortisol/GR alpha (dimer)/p53	0.046	0.15	0.45	21	-0.46	2	23
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.033	0.15	4	-10000	0	4
SGK1	0.045	0.092	-10000	0	-1.3	2	2
IL13	-0.058	0.11	-10000	0	-0.6	3	3
IL6	-0.037	0.19	-10000	0	-0.71	27	27
PRKACG	0.003	0.005	-10000	0	-10000	0	0
IL5	-0.056	0.097	-10000	0	-0.58	2	2
IL2	-0.089	0.13	-10000	0	-0.48	11	11
CDK5	0.01	0.003	-10000	0	-10000	0	0
PRKACB	0.006	0.044	-10000	0	-0.41	6	6
HSP90AA1	0.011	0	-10000	0	-10000	0	0
IL8	-0.05	0.13	-10000	0	-0.42	14	14
CDK5R1/CDK5	0.014	0.013	-10000	0	-0.22	1	1
NF kappa B1 p50/RelA/PKAc	-0.001	0.085	-10000	0	-0.31	11	11
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.043	0.14	0.41	24	-0.42	2	26
SMARCA4	0.012	0.002	-10000	0	-10000	0	0
chromatin remodeling	0.026	0.11	0.3	13	-0.43	4	17
NF kappa B1 p50/RelA/Cbp	0.021	0.1	-10000	0	-0.34	9	9
JUN (dimer)	-0.041	0.1	-10000	0	-0.36	16	16
YWHAH	0.011	0	-10000	0	-10000	0	0
VIPR1	0.012	0.088	-10000	0	-0.41	7	7
NR3C1	-0.015	0.16	0.32	13	-0.4	65	78
NR4A1	-0.022	0.12	-10000	0	-0.43	44	44
TIF2/SUV420H1	0.006	0.054	-10000	0	-0.28	19	19
MAPKKK cascade	-0.078	0.19	0.47	8	-0.59	28	36
cortisol/GR alpha (dimer)/Src-1	0.04	0.15	0.44	21	-0.4	4	25
PBX1	-0.01	0.096	-10000	0	-0.34	38	38
POU1F1	-0.003	0.049	-10000	0	-0.25	19	19
SELE	-0.098	0.32	-10000	0	-0.93	65	65
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.026	0.11	0.3	13	-0.43	4	17
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.043	0.14	0.41	24	-0.42	2	26
mol:cortisol	0.024	0.075	0.28	19	-10000	0	19
MMP1	-0.12	0.11	-10000	0	-0.32	3	3

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.032	0.13	-9999	-0.55	3	3
CRP	0.026	0.13	-9999	-0.52	6	6
cell cycle arrest	0.026	0.14	-9999	-0.53	10	10
TIMP1	0.028	0.12	-9999	-0.57	4	4
IL6ST	-0.052	0.15	-9999	-0.41	86	86
Rac1/GDP	-0.001	0.12	-9999	-0.35	37	37
AP1	-0.021	0.12	-9999	-0.5	11	11
GAB2	0.009	0.036	-9999	-0.41	4	4
TNFSF11	0.013	0.14	-9999	-0.53	6	6
HSP90B1	0.032	0.03	-9999	-10000	0	0
GAB1	0.008	0.036	-9999	-0.41	4	4
MAPK14	-0.026	0.13	-9999	-0.38	39	39
AKT1	0.042	0.039	-9999	-0.39	2	2
FOXO1	0.045	0.04	-9999	-0.37	2	2
MAP2K6	-0.032	0.14	-9999	-0.38	44	44
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	0.015	0.12	-9999	-0.35	29	29
MITF	-0.031	0.15	-9999	-0.39	57	57
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.011	0	-9999	-10000	0	0
A2M	0.012	0.078	-9999	-1.3	2	2
CEBPB	0.017	0.002	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.012	0.085	-9999	-0.63	5	5
STAT3	0.028	0.14	-9999	-0.56	10	10
STAT1	0.002	0.014	-9999	-10000	0	0
CEBPD	0.031	0.13	-9999	-0.6	6	6
PIK3CA	0.012	0.018	-9999	-0.41	1	1
PI3K	0.015	0.031	-9999	-0.28	6	6
JUN	0.006	0.047	-9999	-0.41	7	7
PIAS3/MITF	-0.025	0.14	-9999	-0.37	56	56
MAPK11	-0.027	0.13	-9999	-0.38	39	39
STAT3 (dimer)/FOXO1	0.061	0.13	-9999	-0.46	7	7
GRB2/SOS1/GAB family	-0.043	0.1	-9999	-0.37	33	33
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.02	0.13	-9999	-0.3	67	67
GRB2	0.012	0.001	-9999	-10000	0	0
JAK2	0.004	0.054	-9999	-0.41	9	9
LBP	0.018	0.12	-9999	-0.52	2	2
PIK3R1	0.008	0.04	-9999	-0.41	5	5
JAK1	0.012	0.025	-9999	-0.4	2	2
MYC	0.021	0.18	-9999	-0.93	11	11
FGG	0.025	0.13	-9999	-0.53	5	5
macrophage differentiation	0.026	0.14	-9999	-0.53	10	10
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.041	0.12	-9999	-0.3	63	63
JUNB	0.025	0.15	-9999	-0.76	8	8
FOS	-0.12	0.19	-9999	-0.41	167	167
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.018	0.13	-9999	-0.34	54	54
STAT1/PIAS1	0.001	0.12	-9999	-0.33	35	35
GRB2/SOS1/GAB family/SHP2/PI3K	0.033	0.041	-9999	-0.33	4	4
STAT3 (dimer)	0.029	0.14	-9999	-0.55	10	10
PRKCD	0.029	0.12	-9999	-0.44	11	11
IL6R	-0.022	0.12	-9999	-0.41	46	46
SOCS3	-0.026	0.14	-9999	-0.65	9	9
gp130 (dimer)/JAK1/JAK1/LMO4	-0.008	0.094	-9999	-0.22	88	88
Rac1/GTP	0.002	0.12	-9999	-0.35	36	36
HCK	0.006	0.038	-9999	-0.33	7	7
MAPKKK cascade	0.026	0.081	-9999	-0.77	4	4
bone resorption	0.014	0.13	-9999	-0.51	6	6
IRF1	0.032	0.13	-9999	-0.55	3	3
mol:GDP	-0.01	0.13	-9999	-0.36	39	39
SOS1	0.011	0.001	-9999	-10000	0	0
VAV1	-0.01	0.13	-9999	-0.37	39	39
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.039	0.16	-9999	-0.46	49	49
PTPN11	0.002	0.014	-9999	-10000	0	0
IL6/IL6RA	-0.015	0.1	-9999	-0.29	65	65
gp130 (dimer)/TYK2/TYK2/LMO4	-0.011	0.092	-9999	-0.22	86	86
gp130 (dimer)/JAK2/JAK2/LMO4	-0.015	0.098	-9999	-0.23	93	93
IL6	-0.003	0.083	-9999	-0.38	25	25
PIAS3	0.011	0	-9999	-10000	0	0
PTPRE	0.003	0.024	-9999	-0.37	2	2
PIAS1	0.011	0	-9999	-10000	0	0
RAC1	0.011	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.03	0.13	-9999	-0.25	115	115
LMO4	0.015	0.005	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	0.018	0.13	-9999	-0.54	10	10
MCL1	0.046	0.036	-9999	-0.35	2	2

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.009	0.036	-9999	-0.41	4	4
ELF1	0.009	0.046	-9999	-0.38	5	5
CCNA2	-0.062	0.14	-9999	-0.33	117	117
PIK3CA	0.011	0.018	-9999	-0.41	1	1
JAK3	0.009	0.029	-9999	-0.33	4	4
PIK3R1	0.008	0.04	-9999	-0.41	5	5
JAK1	0.01	0.025	-9999	-0.41	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.053	0.044	-9999	-0.51	1	1
SHC1	0.012	0	-9999	-10000	0	0
SP1	-0.043	0.12	-9999	-0.3	102	102
IL2RA	0.013	0.059	-9999	-0.34	5	5
IL2RB	0.011	0.018	-9999	-0.41	1	1
SOS1	0.012	0	-9999	-10000	0	0
IL2RG	0.006	0.047	-9999	-0.36	9	9
G1/S transition of mitotic cell cycle	-0.1	0.27	-9999	-0.64	103	103
PTPN11	0.012	0	-9999	-10000	0	0
CCND2	-0.1	0.26	-9999	-0.65	102	102
LCK	0.008	0.034	-9999	-0.34	5	5
GRB2	0.012	0	-9999	-10000	0	0
IL2	-0.006	0.06	-9999	-0.33	18	18
CDK6	0.001	0.064	-9999	-0.41	13	13
CCND3	0.056	0.04	-9999	-0.43	1	1

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.1	0.18	-9999	-0.41	143	143
CDC42/GTP	-0.03	0.1	-9999	-0.35	14	14
PLCG1	-0.031	0.1	-9999	-0.36	14	14
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.016	0	-9999	-10000	0	0
cell migration	-0.03	0.099	-9999	-0.34	14	14
S1PR5	0	0.063	-9999	-0.35	17	17
S1PR4	0.009	0.029	-9999	-0.38	3	3
MAPK3	-0.031	0.1	-9999	-0.36	14	14
MAPK1	-0.031	0.1	-9999	-0.36	14	14
S1P/S1P5/Gi	-0.042	0.11	-9999	-0.21	147	147
GNAI1	0.005	0.051	-9999	-0.41	8	8
CDC42/GDP	0.008	0	-9999	-10000	0	0
S1P/S1P5/G12	0.008	0.036	-9999	-0.19	17	17
RHOA	0.024	0.014	-9999	-0.18	2	2
S1P/S1P4/Gi	-0.039	0.11	-9999	-0.21	145	145
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.002	0.073	-9999	-0.41	17	17
S1P/S1P4/G12/G13	0.02	0.016	-9999	-0.2	2	2
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.001	-9999	-10000	0	0
SMARCC1	0.007	0.016	-9999	-10000	0	0
REL	0.011	0.001	-9999	-10000	0	0
HDAC7	0.02	0.066	-9999	-0.31	2	2
JUN	0.006	0.047	-9999	-0.41	7	7
EP300	0.011	0	-9999	-10000	0	0
KAT2B	0.004	0.054	-9999	-0.41	9	9
KAT5	0.011	0	-9999	-10000	0	0
MAPK14	-0.01	0.078	-9999	-0.21	69	69
FOXO1	0.009	0.031	-9999	-0.41	3	3
T-DHT/AR	0.019	0.071	-9999	-0.3	3	3
MAP2K6	-0.031	0.11	-9999	-0.33	69	69
BRM/BAF57	0.008	0.05	-9999	-0.28	16	16
MAP2K4	0.011	0.018	-9999	-0.41	1	1
SMARCA2	-0.001	0.071	-9999	-0.41	16	16
PDE9A	-0.02	0.1	-9999	-0.96	4	4
NCOA2	-0.004	0.077	-9999	-0.41	19	19
CEBPA	0.007	0.037	-9999	-0.38	5	5
EHMT2	0.011	0.001	-9999	-10000	0	0
cell proliferation	0.011	0.12	-9999	-0.37	20	20
NR0B1	-0.014	0.076	-9999	-0.33	30	30
EGR1	-0.044	0.14	-9999	-0.41	71	71
RXRs/9cRA	-0.011	0.078	-9999	-0.2	79	79
AR/RACK1/Src	0.008	0.069	-9999	-0.29	5	5
AR/GR	-0.048	0.12	-9999	-0.25	104	104
GNB2L1	0.011	0.002	-9999	-10000	0	0
PKN1	0.011	0	-9999	-10000	0	0
RCHY1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.016	0.034	-9999	-0.28	7	7
T-DHT/AR/TIF2/CARM1	0.004	0.083	-9999	-0.32	14	14
SRC	0.011	0.06	-9999	-0.28	2	2
NR3C1	-0.05	0.15	-9999	-0.41	79	79
KLK3	-0.048	0.092	-9999	-0.42	6	6
APPBP2	0.012	0.002	-9999	-10000	0	0
TRIM24	0.011	0.002	-9999	-10000	0	0
T-DHT/AR/TIP60	0.004	0.063	-9999	-0.36	2	2
TMPRSS2	-0.031	0.14	-9999	-1	8	8
RXRG	-0.049	0.14	-9999	-0.4	79	79
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.011	0	-9999	-10000	0	0
RXRB	0.011	0	-9999	-10000	0	0
CARM1	0.011	0.002	-9999	-10000	0	0
NR2C2	0.003	0.059	-9999	-0.41	11	11
KLK2	-0.012	0.16	-9999	-0.54	37	37
AR	-0.023	0.099	-9999	-0.22	93	93
SENP1	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
MDM2	0.011	0.002	-9999	-10000	0	0
SRY	0	0.002	-9999	-10000	0	0
GATA2	-0.03	0.12	-9999	-0.41	53	53
MYST2	0.011	0	-9999	-10000	0	0
HOXB13	-0.22	0.16	-9999	-0.33	363	363
T-DHT/AR/RACK1/Src	0.009	0.065	-9999	-0.31	3	3
positive regulation of transcription	-0.03	0.12	-9999	-0.41	53	53
DNAJA1	0.012	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.001	-9999	-10000	0	0
NCOA1	0.013	0.02	-9999	-0.44	1	1
SPDEF	-0.11	0.17	-9999	-0.34	190	190
T-DHT/AR/TIF2	0.01	0.073	-9999	-0.29	16	16
T-DHT/AR/Hsp90	0.004	0.063	-9999	-0.36	2	2
GSK3B	0.011	0.002	-9999	-10000	0	0
NR2C1	0.011	0	-9999	-10000	0	0
mol:T-DHT	0.006	0.064	-9999	-0.22	7	7
SIRT1	0.009	0.025	-9999	-0.41	2	2
ZMIZ2	0.011	0.002	-9999	-10000	0	0
POU2F1	0.021	0.011	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.009	0.071	-9999	-0.31	5	5
CREBBP	0.009	0.025	-9999	-0.41	2	2
SMARCE1	0.011	0.001	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.063	-10000	0	-0.65	4	4
HDAC1	0.008	0.005	-10000	0	-10000	0	0
AES	0.01	0.001	-10000	0	-10000	0	0
FBXW11	0.011	0	-10000	0	-10000	0	0
DTX1	0.006	0.044	-10000	0	-0.41	6	6
LRP6/FZD1	0.015	0.018	-10000	0	-0.28	2	2
TLE1	0.01	0.018	-10000	0	-0.41	1	1
AP1	-0.064	0.12	-10000	0	-0.24	172	172
NCSTN	0.011	0	-10000	0	-10000	0	0
ADAM10	0.008	0.036	-10000	0	-0.41	4	4
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.03	0.052	-10000	0	-0.56	2	2
NICD/RBPSUH	0.023	0.046	-10000	0	-0.5	4	4
WIF1	-0.097	0.16	-10000	0	-0.35	163	163
NOTCH1	-0.004	0.046	-10000	0	-0.53	4	4
PSENEN	0.011	0	-10000	0	-10000	0	0
KREMEN2	-0.021	0.099	-10000	0	-0.33	51	51
DKK1	-0.065	0.14	-10000	0	-0.33	119	119
beta catenin/beta TrCP1	0.026	0.027	-10000	0	-10000	0	0
APH1B	0.006	0.047	-10000	0	-0.41	7	7
APH1A	0.011	0	-10000	0	-10000	0	0
AXIN1	0.001	0.019	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.017	0.027	0.19	1	-0.21	3	4
PSEN1	0.011	0	-10000	0	-10000	0	0
FOS	-0.12	0.19	-10000	0	-0.41	167	167
JUN	0.006	0.047	-10000	0	-0.41	7	7
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
CTNNB1	0.02	0.029	-10000	0	-10000	0	0
MAPK3	0.011	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.011	0.083	-10000	0	-0.25	35	35
HNF1A	0.005	0.041	-10000	0	-0.33	8	8
CTBP1	0.01	0.001	-10000	0	-10000	0	0
MYC	-0.003	0.17	-10000	0	-1.3	10	10
NKD1	-0.021	0.1	-10000	0	-0.34	48	48
FZD1	0.009	0.025	-10000	0	-0.41	2	2
NOTCH1 precursor/Deltex homolog 1	0.021	0.05	-10000	0	-0.5	4	4
apoptosis	-0.064	0.12	-10000	0	-0.24	172	172
Delta 1/NOTCHprecursor	0.017	0.067	-10000	0	-0.64	4	4
DLL1	-0.003	0.075	-10000	0	-0.41	18	18
PPARD	0.018	0.013	-10000	0	-10000	0	0
Gamma Secretase	0.031	0.024	-10000	0	-0.19	1	1
APC	0.001	0.019	-10000	0	-0.18	2	2
DVL1	0	0.015	-10000	0	-10000	0	0
CSNK2A1	0.011	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.039	0.096	-10000	0	-0.18	163	163
LRP6	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.011	0.001	-10000	0	-10000	0	0
NLK	0.011	0.006	-10000	0	-10000	0	0
CCND1	0.018	0.019	-10000	0	-10000	0	0
WNT1	0.004	0.041	-10000	0	-0.33	8	8
Axin1/APC/beta catenin	0.029	0.025	-10000	0	-10000	0	0
DKK2	-0.015	0.1	-10000	0	-0.4	34	34
NOTCH1 precursor/DVL1	0	0.04	-10000	0	-0.46	4	4
GSK3B	0.011	0	-10000	0	-10000	0	0
FRAT1	0.01	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.006	0.047	-10000	0	-0.51	4	4
PPP2R5D	0.012	0.046	0.21	11	-10000	0	11
MAPK1	0.011	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.033	0.089	-10000	0	-0.21	39	39
RBPJ	0.011	0	-10000	0	-10000	0	0
CREBBP	0.012	0.026	-10000	0	-0.41	2	2

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.075	0.11	-9999	-0.36	37	37
TC10/GTP	-0.055	0.076	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.001	0.069	-9999	-0.21	54	54
HRAS	0.011	0	-9999	-10000	0	0
APS homodimer	0.011	0	-9999	-10000	0	0
GRB14	-0.11	0.16	-9999	-0.33	196	196
FOXO3	-0.009	0.036	-9999	-0.57	2	2
AKT1	-0.031	0.091	-9999	-0.28	28	28
INSR	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.03	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0.018	-9999	-0.41	1	1
SORBS1	-0.13	0.2	-9999	-0.41	187	187
CRK	0.011	0	-9999	-10000	0	0
PTPN1	0.027	0.001	-9999	-10000	0	0
CAV1	-0.036	0.11	-9999	-0.23	126	126
CBL/APS/CAP/Crk-II/C3G	-0.04	0.1	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.001	0.069	-9999	-0.21	54	54
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.019	0.057	-9999	-0.18	58	58
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.013	0.055	-9999	-10000	0	0
RPS6KB1	-0.023	0.086	-9999	-0.25	28	28
PARD6A	0.011	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.003	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.047	0.066	-9999	-0.26	28	28
HRAS/GTP	-0.014	0.043	-9999	-10000	0	0
Insulin Receptor	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.008	0.065	-9999	-0.19	47	47
PRKCI	-0.012	0.018	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.059	0.08	-9999	-0.3	28	28
SHC1	0.011	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.002	0.028	-9999	-0.39	2	2
PI3K	-0.02	0.058	-9999	-0.18	58	58
NCK2	0.011	0	-9999	-10000	0	0
RHOQ	0.011	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.008	0	-9999	-10000	0	0
AKT2	-0.031	0.091	-9999	-0.28	28	28
PRKCZ	-0.013	0.028	-9999	-0.52	1	1
SH2B2	0.011	0	-9999	-10000	0	0
SHC/SHIP	0.007	0.061	-9999	-0.18	55	55
F2RL2	-0.016	0.1	-9999	-0.4	35	35
TRIP10	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.017	0.002	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.029	0.001	-9999	-10000	0	0
RAPGEF1	0.011	0	-9999	-10000	0	0
RASA1	0.007	0.04	-9999	-0.41	5	5
NCK1	0.009	0.025	-9999	-0.41	2	2
CBL/APS/CAP/Crk-II	-0.05	0.11	-9999	-0.2	187	187
TC10/GDP	0.008	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.024	0.01	-9999	-0.21	1	1
INPP5D	0	0.064	-9999	-0.19	55	55
SOS1	0.011	0	-9999	-10000	0	0
SGK1	-0.006	0.05	-9999	-0.82	2	2
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.011	0	-9999	-10000	0	0
IRS1	-0.031	0.13	-9999	-0.41	54	54
p62DOK/RasGAP	-0.002	0.028	-9999	-0.4	2	2
INS	0.003	0.002	-9999	-10000	0	0
mol:PI-3-4-P2	0	0.064	-9999	-0.19	55	55
GRB2	0.011	0	-9999	-10000	0	0
EIF4EBP1	-0.026	0.089	-9999	-0.26	32	32
PTPRA	0.012	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
TC10/GTP/CIP4	0.015	0	-9999	-10000	0	0
PDPK1	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.006	0.065	-9999	-0.19	47	47
Insulin Receptor/Insulin/IRS1	-0.006	0.069	-9999	-0.22	54	54
Insulin Receptor/Insulin/IRS3	0.012	0.002	-9999	-10000	0	0
Par3/Par6	0.013	0.051	-9999	-0.19	32	32

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.16	0.21	-9999	-0.41	216	216
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0.015	-9999	-0.33	1	1
TCEB1	0.011	0	-9999	-10000	0	0
HIF1A/p53	0.025	0.01	-9999	-10000	0	0
HIF1A	0.02	0.005	-9999	-10000	0	0
COPS5	0.011	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.032	0.012	-9999	-10000	0	0
FIH (dimer)	0.011	0	-9999	-10000	0	0
CDKN2A	-0.13	0.17	-9999	-0.33	228	228
ARNT/IPAS	-0.1	0.14	-9999	-0.28	216	216
HIF1AN	0.011	0	-9999	-10000	0	0
GNB2L1	0.011	0	-9999	-10000	0	0
HIF1A/ARNT	0.026	0.005	-9999	-10000	0	0
CUL2	0.011	0	-9999	-10000	0	0
OS9	0.011	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.022	0.008	-9999	-0.17	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.026	0.005	-9999	-10000	0	0
PHD1-3/OS9	0.027	0.016	-9999	-0.2	1	1
HIF1A/RACK1/Elongin B/Elongin C	0.034	0.008	-9999	-10000	0	0
VHL	0.01	0.018	-9999	-0.41	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
HIF1A/JAB1	0.026	0.005	-9999	-10000	0	0
EGLN3	0.008	0.031	-9999	-0.35	4	4
EGLN2	0.011	0	-9999	-10000	0	0
EGLN1	0.011	0	-9999	-10000	0	0
TP53	0.01	0.018	-9999	-0.41	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.03	0.023	-9999	-0.5	1	1
ARNT	0.011	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.011	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.037	0.074	-9999	-0.19	1	1

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.007	0.085	-10000	0	-0.41	23	23
Jak2/Leptin Receptor	-0.097	0.14	-10000	0	-0.35	86	86
PTP1B/AKT1	0.017	0.04	-10000	0	-0.2	5	5
FYN	0.011	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.013	0.044	-10000	0	-0.23	5	5
EGFR	0.001	0.067	-10000	0	-0.41	14	14
EGF/EGFR	-0.016	0.05	-10000	0	-0.24	18	18
CSF1	0.003	0.057	-10000	0	-0.41	10	10
AKT1	0.011	0.001	-10000	0	-10000	0	0
INSR	0.011	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.012	0.089	-10000	0	-0.26	30	30
Insulin Receptor/Insulin	-0.008	0.022	-10000	0	-10000	0	0
HCK	0.007	0.038	-10000	0	-0.33	7	7
CRK	0.011	0	-10000	0	-10000	0	0
TYK2	0.018	0.041	-10000	0	-0.22	5	5
EGF	-0.005	0.073	-10000	0	-0.34	25	25
YES1	0.011	0	-10000	0	-10000	0	0
CAV1	-0.002	0.077	-10000	0	-0.3	13	13
TXN	0.011	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.004	0.078	-10000	0	-0.24	32	32
cell migration	-0.013	0.044	0.23	5	-10000	0	5
STAT3	0.011	0.001	-10000	0	-10000	0	0
PRLR	-0.075	0.17	-10000	0	-0.41	111	111
ITGA2B	0.004	0.05	-10000	0	-0.4	8	8
CSF1R	0.008	0.034	-10000	0	-0.39	4	4
Prolactin Receptor/Prolactin	-0.059	0.13	-10000	0	-0.29	128	128
FGR	0.002	0.059	-10000	0	-0.41	11	11
PTP1B/p130 Cas	0.018	0.041	-10000	0	-0.22	5	5
Crk/p130 Cas	0.023	0.04	-10000	0	-0.2	5	5
DOK1	0.015	0.06	-10000	0	-0.24	16	16
JAK2	-0.039	0.13	-10000	0	-0.27	81	81
Jak2/Leptin Receptor/Leptin	-0.014	0.051	-10000	0	-0.38	7	7
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
PTPN1	0.013	0.044	-10000	0	-0.23	5	5
LYN	0.011	0	-10000	0	-10000	0	0
CDH2	-0.052	0.15	-10000	0	-0.41	81	81
SRC	0.019	0.019	-10000	0	-10000	0	0
ITGB3	-0.068	0.16	-10000	0	-0.41	102	102
CAT1/PTP1B	0.017	0.072	-10000	0	-0.31	7	7
CAPN1	0.012	0.001	-10000	0	-10000	0	0
CSK	0.011	0	-10000	0	-10000	0	0
PI3K	-0.007	0.025	-10000	0	-0.23	2	2
mol:H2O2	0	0.001	-10000	0	-10000	0	0
STAT3 (dimer)	-0.012	0.047	-10000	0	-0.35	7	7
negative regulation of transcription	-0.038	0.12	-10000	0	-0.25	100	100
FCGR2A	0.01	0.015	-10000	0	-0.33	1	1
FER	0.011	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.044	0.12	-10000	0	-0.28	110	110
BLK	-0.015	0.087	-10000	0	-0.33	39	39
Insulin Receptor/Insulin/Shc	0.016	0.002	-10000	0	-10000	0	0
RHOA	0.012	0.001	-10000	0	-10000	0	0
LEPR	-0.11	0.19	-10000	0	-0.41	161	161
BCAR1	0.011	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.011	0	-10000	0	-10000	0	0
mol:NADPH	0.001	0.001	-10000	0	-10000	0	0
TRPV6	0.012	0.068	-10000	0	-0.37	5	5
PRL	-0.01	0.083	-10000	0	-0.39	24	24
SOCS3	0.005	0.075	-10000	0	-1.2	2	2
SPRY2	0.006	0.044	-10000	0	-0.42	6	6
Insulin Receptor/Insulin/IRS1	-0.009	0.075	-10000	0	-0.24	54	54
CSF1/CSF1R	0.018	0.056	-10000	0	-0.25	13	13
Ras protein signal transduction	0.008	0.014	-10000	0	-10000	0	0
IRS1	-0.031	0.13	-10000	0	-0.41	54	54
INS	0.001	0.003	-10000	0	-10000	0	0
LEP	0.005	0.025	-10000	0	-0.33	3	3
STAT5B	-0.004	0.065	-10000	0	-0.23	20	20
STAT5A	-0.004	0.064	-10000	0	-0.23	19	19
GRB2	0.011	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.064	-10000	0	-0.26	18	18
CSN2	-0.031	0.061	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
LAT	0.019	0.019	-10000	0	-10000	0	0
YBX1	0.017	0.018	-10000	0	-0.4	1	1
LCK	0.008	0.034	-10000	0	-0.34	5	5
SHC1	0.011	0	-10000	0	-10000	0	0
NOX4	0.007	0.039	-10000	0	-0.4	5	5

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.012	0.004	-10000	0	-10000	0	0
HSPA8	0.011	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.029	0.088	0.17	1	-0.26	65	66
AKT1	0.013	0.002	-10000	0	-10000	0	0
GSC	-0.029	0.077	-10000	0	-10000	0	0
NKX2-5	-0.05	0.12	-10000	0	-0.34	84	84
muscle cell differentiation	0.044	0.097	0.36	22	-10000	0	22
SMAD2-3/SMAD4/SP1	0.038	0.051	-10000	0	-0.26	3	3
SMAD4	0.007	0.035	-10000	0	-0.42	1	1
CBFB	0.011	0	-10000	0	-10000	0	0
SAP18	0.011	0	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.017	0.044	-10000	0	-0.19	21	21
SMAD3/SMAD4/VDR	0.005	0.041	-10000	0	-0.22	4	4
MYC	0.001	0.057	-10000	0	-0.41	10	10
CDKN2B	0.025	0.031	-10000	0	-10000	0	0
AP1	-0.025	0.12	-10000	0	-0.35	23	23
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.044	0.02	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.012	0.045	-10000	0	-0.34	3	3
SP3	0.013	0	-10000	0	-10000	0	0
CREB1	0.011	0	-10000	0	-10000	0	0
FOXH1	-0.08	0.15	-10000	0	-0.34	135	135
SMAD3/SMAD4/GR	-0.036	0.096	-10000	0	-0.25	82	82
GATA3	-0.004	0.071	-10000	0	-0.35	20	20
SKI/SIN3/HDAC complex/NCoR1	0.036	0.013	-10000	0	-10000	0	0
MEF2C/TIF2	-0.07	0.18	-10000	0	-0.45	68	68
endothelial cell migration	-0.015	0.11	1.2	4	-10000	0	4
MAX	0.01	0.004	-10000	0	-10000	0	0
RBBP7	0.011	0	-10000	0	-10000	0	0
RBBP4	0.009	0.031	-10000	0	-0.41	3	3
RUNX2	0.001	0.058	-10000	0	-0.33	16	16
RUNX3	0.002	0.054	-10000	0	-0.33	14	14
RUNX1	0.011	0	-10000	0	-10000	0	0
CTBP1	0.011	0	-10000	0	-10000	0	0
NR3C1	-0.052	0.15	-10000	0	-0.41	79	79
VDR	0.003	0.052	-10000	0	-0.33	13	13
CDKN1A	0.054	0.066	-10000	0	-1.2	1	1
KAT2B	0.004	0.054	-10000	0	-0.41	9	9
SMAD2/SMAD2/SMAD4/FOXH1	-0.036	0.1	-10000	0	-0.24	48	48
DCP1A	0.011	0	-10000	0	-10000	0	0
SKI	0.011	0	-10000	0	-10000	0	0
SERPINE1	0.015	0.11	-10000	0	-1.3	4	4
SMAD3/SMAD4/ATF2	0.011	0.048	-10000	0	-0.3	7	7
SMAD3/SMAD4/ATF3	-0.01	0.089	-10000	0	-0.27	50	50
SAP30	0.011	0	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.026	0.019	-10000	0	-0.22	2	2
JUN	-0.025	0.12	-10000	0	-0.38	19	19
SMAD3/SMAD4/IRF7	0.006	0.055	-10000	0	-0.29	8	8
TFE3	0.016	0.005	-10000	0	-10000	0	0
COL1A2	0.008	0.086	-10000	0	-0.79	5	5
mesenchymal cell differentiation	-0.006	0.059	0.27	16	-10000	0	16
DLX1	-0.031	0.11	-10000	0	-0.33	63	63
TCF3	0.011	0	-10000	0	-10000	0	0
FOS	-0.12	0.2	-10000	0	-0.41	167	167
SMAD3/SMAD4/Max	0.001	0.036	-10000	0	-0.26	5	5
Cbp/p300/SNIP1	0.023	0.016	-10000	0	-0.23	2	2
ZBTB17	0.009	0.002	-10000	0	-10000	0	0
LAMC1	0.033	0.036	-10000	0	-0.26	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	0.013	0.04	-10000	0	-0.25	5	5
IRF7	0.004	0.05	-10000	0	-0.35	10	10
ESR1	-0.038	0.13	-10000	0	-0.41	62	62
HNF4A	-0.04	0.12	-10000	0	-0.33	78	78
MEF2C	-0.073	0.17	-10000	0	-0.43	80	80
SMAD2-3/SMAD4	0.017	0.048	-10000	0	-0.28	4	4
Cbp/p300/Src-1	0.023	0.019	-10000	0	-0.22	3	3
IGHV3OR16-13	-0.001	0.008	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.011	0	-10000	0	-10000	0	0
CREBBP	0.01	0.026	-10000	0	-0.41	2	2
SKIL	0.011	0	-10000	0	-10000	0	0
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC2	0.011	0	-10000	0	-10000	0	0
SNIP1	0.011	0.001	-10000	0	-10000	0	0
GCN5L2	0.001	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.03	0.044	-10000	0	-0.26	4	4
MSG1/HSC70	0.004	0.046	-10000	0	-0.23	20	20
SMAD2	0.008	0.018	-10000	0	-10000	0	0
SMAD3	0.009	0.046	-10000	0	-0.45	4	4
SMAD3/E2F4-5/DP1/p107/SMAD4	0.026	0.033	-10000	0	-0.22	4	4
SMAD2/SMAD2/SMAD4	0.002	0.042	-10000	0	-0.28	10	10
NCOR1	0.011	0	-10000	0	-10000	0	0
NCOA2	-0.004	0.077	-10000	0	-0.41	19	19
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
MYOD/E2A	-0.011	0.068	-10000	0	-0.22	53	53
SMAD2-3/SMAD4/SP1/MIZ-1	0.043	0.049	-10000	0	-0.24	3	3
IFNB1	0.014	0.063	-10000	0	-0.32	10	10
SMAD3/SMAD4/MEF2C	-0.065	0.17	-10000	0	-0.46	62	62
CITED1	-0.002	0.066	-10000	0	-0.34	20	20
SMAD2-3/SMAD4/ARC105	0.023	0.044	-10000	0	-0.24	4	4
RBL1	0.011	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.041	0.037	-10000	0	-0.34	2	2
RUNX1-3/PEBPB2	0.017	0.031	-10000	0	-10000	0	0
SMAD7	0	0.13	-10000	0	-0.48	12	12
MYC/MIZ-1	0.007	0.04	-10000	0	-0.28	10	10
SMAD3/SMAD4	0.012	0.055	-10000	0	-0.4	4	4
IL10	0.009	0.091	-10000	0	-0.29	34	34
PIASy/HDAC complex	0.01	0.003	-10000	0	-10000	0	0
PIAS3	0.011	0.002	-10000	0	-10000	0	0
CDK2	0.012	0.003	-10000	0	-10000	0	0
IL5	0.011	0.064	-10000	0	-0.4	2	2
CDK4	0.012	0.003	-10000	0	-10000	0	0
PIAS4	0.01	0.003	-10000	0	-10000	0	0
ATF3	-0.025	0.12	-10000	0	-0.41	47	47
SMAD3/SMAD4/SP1	0.033	0.048	-10000	0	-0.25	5	5
FOXG1	-0.16	0.17	-10000	0	-0.33	262	262
FOXO3	0.022	0.003	-10000	0	-10000	0	0
FOXO1	0.02	0.022	-10000	0	-0.28	3	3
FOXO4	0.021	0.018	-10000	0	-0.28	2	2
heart looping	-0.072	0.17	-10000	0	-0.42	80	80
CEBPB	0.012	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.012	0.08	-10000	0	-0.25	31	31
MYOD1	-0.028	0.099	-10000	0	-0.33	53	53
SMAD3/SMAD4/HNF4	-0.016	0.079	-10000	0	-0.22	32	32
SMAD3/SMAD4/GATA3	-0.001	0.07	-10000	0	-0.31	8	8
SnoN/SIN3/HDAC complex/NCoR1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.027	0.045	-10000	0	-0.24	2	2
SMAD3/SMAD4/SP1-3	0.041	0.046	-10000	0	-0.25	2	2
MED15	0.011	0	-10000	0	-10000	0	0
SP1	0.018	0.013	-10000	0	-10000	0	0
SIN3B	0.011	0	-10000	0	-10000	0	0
SIN3A	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.061	0.14	-10000	0	-0.36	59	59
ITGB5	0.043	0.036	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.037	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.032	0.11	-10000	0	-0.25	95	95
AR	-0.061	0.16	-10000	0	-0.41	93	93
negative regulation of cell growth	0.019	0.061	-10000	0	-0.3	5	5
SMAD3/SMAD4/MYOD	-0.009	0.07	-10000	0	-0.22	26	26
E2F5	0.011	0	-10000	0	-10000	0	0
E2F4	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.016	0.085	-10000	0	-0.25	13	13
SMAD2-3/SMAD4/FOXO1-3a-4	0.038	0.037	-10000	0	-0.35	2	2
TFDP1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.019	0.12	-10000	0	-0.34	25	25
SMAD3/SMAD4/RUNX2	0.007	0.059	-10000	0	-0.27	16	16
TGIF2	0.011	0	-10000	0	-10000	0	0
TGIF1	0.011	0	-10000	0	-10000	0	0
ATF2	0.009	0.031	-10000	0	-0.41	3	3

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.007	0.085	-9999	-0.41	23	23
alphaV beta3 Integrin	-0.039	0.12	-9999	-0.28	102	102
PTK2	-0.037	0.086	-9999	-0.38	23	23
positive regulation of JNK cascade	-0.014	0.057	-9999	-0.28	23	23
CDC42/GDP	0.019	0.088	-9999	-0.38	23	23
Rac1/GDP	0.02	0.087	-9999	-0.37	23	23
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.011	0	-9999	-10000	0	0
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.017	0.07	-9999	-0.35	23	23
nectin-3/I-afadin	0.004	0.06	-9999	-0.28	23	23
RAPGEF1	0.012	0.094	-9999	-0.42	23	23
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.006	0.11	-9999	-0.47	23	23
PDGFB-D/PDGFRB	-0.007	0.085	-9999	-0.41	23	23
TLN1	0.001	0.076	-9999	-0.26	35	35
Rap1/GTP	-0.014	0.06	-9999	-0.3	23	23
IQGAP1	0.011	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.021	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.004	0.06	-9999	-0.28	23	23
PVR	0.011	0	-9999	-10000	0	0
Necl-5(dimer)	0.011	0	-9999	-10000	0	0
mol:GDP	0.014	0.1	-9999	-0.46	23	23
MLLT4	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PI3K	0.013	0.069	-9999	-0.21	46	46
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.016	0.014	-9999	-0.22	2	2
positive regulation of lamellipodium assembly	-0.015	0.06	-9999	-0.3	23	23
PVRL1	0.01	0.021	-9999	-0.33	2	2
PVRL3	-0.007	0.085	-9999	-0.41	23	23
PVRL2	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
CDH1	0.009	0.025	-9999	-0.41	2	2
CLDN1	-0.043	0.14	-9999	-0.41	70	70
JAM-A/CLDN1	-0.011	0.09	-9999	-0.21	89	89
SRC	-0.001	0.12	-9999	-0.52	23	23
ITGB3	-0.068	0.16	-9999	-0.41	102	102
nectin-1(dimer)/I-afadin/I-afadin	0.016	0.014	-9999	-0.22	2	2
FARP2	0.01	0.1	-9999	-0.45	23	23
RAC1	0.011	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.012	0.05	-9999	-0.23	23	23
nectin-1/I-afadin	0.016	0.014	-9999	-0.22	2	2
nectin-2/I-afadin	0.016	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.015	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.011	0.054	-9999	-0.24	23	23
CDC42/GTP/IQGAP1/filamentous actin	0.015	0	-9999	-10000	0	0
F11R	0.01	0.018	-9999	-0.41	1	1
positive regulation of filopodium formation	-0.014	0.057	-9999	-0.28	23	23
alphaV/beta3 Integrin/Talin	-0.023	0.11	-9999	-0.31	41	41
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.016	0	-9999	-10000	0	0
PIP5K1C	-0.005	0.081	-9999	-0.29	35	35
VAV2	0.009	0.1	-9999	-0.46	23	23
RAP1/GDP	-0.016	0.07	-9999	-0.35	23	23
ITGAV	0.011	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.012	0.05	-9999	-0.23	23	23
nectin-3(dimer)/I-afadin/I-afadin	0.004	0.06	-9999	-0.28	23	23
Rac1/GTP	-0.018	0.073	-9999	-0.36	23	23
PTPRM	-0.013	0.089	-9999	-0.26	57	57
E-cadherin/beta catenin/alpha catenin	-0.001	0.012	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC3	0.011	0	-10000	0	-10000	0	0
VDR	0.003	0.052	-10000	0	-0.33	13	13
Cbp/p300/PCAF	0.017	0.035	-10000	0	-0.23	11	11
EP300	0.011	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.02	0.051	-10000	0	-0.28	7	7
KAT2B	0.004	0.054	-10000	0	-0.41	9	9
MAPK14	0.011	0	-10000	0	-10000	0	0
AKT1	0.012	0.06	0.19	21	-0.24	12	33
RAR alpha/9cRA/Cyclin H	-0.02	0.065	-10000	0	-0.24	39	39
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.017	0.055	-10000	0	-0.23	17	17
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.005	0.068	-10000	0	-0.2	47	47
NCOR2	0.011	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.003	0.036	-10000	0	-0.22	13	13
RXRs/RARs/NRIP1/9cRA	-0.003	0.13	-10000	0	-0.4	45	45
NCOA2	-0.004	0.077	-10000	0	-0.41	19	19
NCOA3	0.01	0.015	-10000	0	-0.33	1	1
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
VDR/VDR/DNA	0.003	0.052	-10000	0	-0.33	13	13
RARG	0.012	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.015	0.001	-10000	0	-10000	0	0
MAPK3	0.012	0.001	-10000	0	-10000	0	0
MAPK1	0.011	0	-10000	0	-10000	0	0
MAPK8	0.007	0.044	-10000	0	-0.41	6	6
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.011	0.12	-10000	0	-0.38	44	44
RARA	-0.004	0.073	-10000	0	-0.23	47	47
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.01	0.07	-10000	0	-0.26	22	22
PRKCA	-0.014	0.1	-10000	0	-0.41	36	36
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.012	0.14	-10000	0	-0.42	45	45
RXRG	-0.053	0.13	-10000	0	-0.3	106	106
RXRA	0.002	0.068	-10000	0	-0.2	47	47
RXRB	-0.013	0.087	-10000	0	-0.28	42	42
VDR/Vit D3/DNA	0.003	0.036	-10000	0	-0.22	13	13
RBP1	-0.007	0.085	-10000	0	-0.41	23	23
CRBP1/9-cic-RA	-0.004	0.06	-10000	0	-0.29	23	23
RARB	0.004	0.06	-10000	0	-0.41	11	11
PRKCG	-0.035	0.12	-10000	0	-0.33	74	74
MNAT1	0.011	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.003	0.14	-10000	0	-0.42	44	44
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.003	0.11	-10000	0	-0.34	43	43
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.069	-10000	0	-0.27	14	14
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.012	0.14	-10000	0	-0.42	45	45
positive regulation of DNA binding	-0.019	0.062	-10000	0	-0.22	39	39
NRIP1	-0.012	0.15	-10000	0	-0.78	10	10
RXRs/RARs	-0.017	0.14	-10000	0	-0.41	47	47
RXRs/RXRs/DNA/9cRA	-0.018	0.12	-10000	0	-0.4	44	44
PRKACA	0.011	0	-10000	0	-10000	0	0
CDK7	0.011	0	-10000	0	-10000	0	0
TFIIH	0.022	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.011	0.039	-10000	0	-0.33	2	2
CCNH	0.011	0	-10000	0	-10000	0	0
CREBBP	0.009	0.025	-10000	0	-0.41	2	2
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.005	0.047	-10000	0	-0.22	22	22
cell-cell adhesion	0.029	0.062	0.3	8	-10000	0	8
Ephrin B/EPHB2/RasGAP	0.008	0.069	-10000	0	-0.38	1	1
ITSN1	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
SHC1	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.006	0.045	-10000	0	-0.2	22	22
Ephrin B1/EPHB1	-0.009	0.073	-10000	0	-0.23	53	53
HRAS/GDP	-0.029	0.066	-10000	0	-0.3	9	9
Ephrin B/EPHB1/GRB7	-0.02	0.097	-10000	0	-0.2	101	101
Endophilin/SYNJ1	0.008	0.062	-10000	0	-0.36	1	1
KRAS	0.01	0.015	-10000	0	-0.33	1	1
Ephrin B/EPHB1/Src	-0.009	0.09	-10000	0	-0.19	99	99
endothelial cell migration	-0.003	0.025	-10000	0	-0.18	10	10
GRB2	0.011	0	-10000	0	-10000	0	0
GRB7	-0.011	0.084	-10000	0	-0.33	34	34
PAK1	0.012	0.067	-10000	0	-0.36	3	3
HRAS	0.011	0	-10000	0	-10000	0	0
RRAS	0.008	0.063	-10000	0	-0.36	1	1
DNM1	0.006	0.044	-10000	0	-0.41	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.01	0.085	-10000	0	-0.36	7	7
lamellipodium assembly	-0.029	0.062	-10000	0	-0.3	8	8
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.008	0.088	-10000	0	-0.21	53	53
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
EPHB2	0.009	0.025	-10000	0	-0.33	3	3
EPHB3	-0.004	0.072	-10000	0	-0.35	22	22
EPHB1	-0.029	0.12	-10000	0	-0.41	52	52
EPHB4	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	-0.001	0.083	-10000	0	-0.22	45	45
Ephrin B/EPHB2	0.004	0.066	-10000	0	-0.19	55	55
Ephrin B/EPHB3	-0.003	0.083	-10000	0	-0.22	58	58
JNK cascade	0.009	0.064	-10000	0	-0.18	52	52
Ephrin B/EPHB1	-0.016	0.09	-10000	0	-0.2	99	99
RAP1/GDP	0.01	0.075	-10000	0	-0.29	7	7
EFNB2	0.009	0.031	-10000	0	-0.41	3	3
EFNB3	-0.029	0.12	-10000	0	-0.41	52	52
EFNB1	0.01	0.018	-10000	0	-0.41	1	1
Ephrin B2/EPHB1-2	-0.002	0.069	-10000	0	-0.2	53	53
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
CDC42/GTP	-0.034	0.072	-10000	0	-0.35	8	8
Rap1/GTP	-0.029	0.061	-10000	0	-0.31	8	8
axon guidance	0.005	0.047	-10000	0	-0.22	22	22
MAPK3	0.004	0.079	-10000	0	-0.32	7	7
MAPK1	0.004	0.079	-10000	0	-0.32	7	7
Rac1/GDP	0.006	0.078	-10000	0	-0.29	9	9
actin cytoskeleton reorganization	-0.023	0.05	-10000	0	-0.25	8	8
CDC42/GDP	0.006	0.078	-10000	0	-0.29	9	9
PI3K	0.022	0.028	-10000	0	-0.19	10	10
EFNA5	-0.003	0.076	-10000	0	-0.4	19	19
Ephrin B2/EPHB4	0.013	0.021	-10000	0	-0.23	4	4
Ephrin B/EPHB2/Intersectin/N-WASP	0.007	0.068	-10000	0	-0.19	55	55
CDC42	0.011	0	-10000	0	-10000	0	0
RAS family/GTP	-0.028	0.06	-10000	0	-0.3	8	8
PTK2	0.006	0.018	-10000	0	-10000	0	0
MAP4K4	0.009	0.065	-10000	0	-0.18	52	52
SRC	0.011	0	-10000	0	-10000	0	0
KALRN	0.007	0.04	-10000	0	-0.41	5	5
Intersectin/N-WASP	0.016	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.018	0.08	-10000	0	-0.28	10	10
MAP2K1	-0.002	0.083	-10000	0	-0.35	7	7
WASL	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.005	0.07	-10000	0	-0.2	52	52
cell migration	-0.003	0.097	-10000	0	-0.37	8	8
NRAS	0.011	0	-10000	0	-10000	0	0
SYNJ1	0.008	0.063	-10000	0	-0.36	1	1
PXN	0.011	0	-10000	0	-10000	0	0
TF	0.005	0.072	-10000	0	-0.32	5	5
HRAS/GTP	-0.032	0.067	-10000	0	-0.33	8	8
Ephrin B1/EPHB1-2	-0.002	0.067	-10000	0	-0.2	56	56
cell adhesion mediated by integrin	0.018	0.067	0.21	55	-10000	0	55
RAC1	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.006	0.086	-10000	0	-0.35	8	8
RAC1-CDC42/GTP	-0.033	0.071	-10000	0	-0.3	19	19
RASA1	0.007	0.04	-10000	0	-0.41	5	5
RAC1-CDC42/GDP	0.01	0.075	-10000	0	-0.27	9	9
ruffle organization	0.01	0.08	-10000	0	-0.31	8	8
NCK1	0.009	0.025	-10000	0	-0.41	2	2
receptor internalization	0.012	0.067	-10000	0	-0.35	5	5
Ephrin B/EPHB2/KALRN	0.008	0.071	-10000	0	-0.38	3	3
ROCK1	0.012	0.04	-10000	0	-0.18	22	22
RAS family/GDP	-0.022	0.05	-10000	0	-0.24	8	8
Rac1/GTP	-0.031	0.065	-10000	0	-0.32	8	8
Ephrin B/EPHB1/Src/Paxillin	-0.013	0.094	-10000	0	-0.2	99	99

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	-0.015	0.082	-10000	0	-0.2	86	86
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.004	0.033	-10000	0	-0.22	12	12
GNB1/GNG2	0.01	0.033	-10000	0	-0.23	10	10
GNB1	0.011	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.026	0.079	-10000	0	-0.22	80	80
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	0.009	0.021	0.061	80	-10000	0	80
GNAL	-0.051	0.15	-10000	0	-0.41	80	80
GNG2	0.003	0.056	-10000	0	-0.4	10	10
CRH	-0.006	0.049	-10000	0	-0.33	12	12
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.03	-10000	0	-0.28	6	6
MAPK11	0.006	0.018	-10000	0	-0.28	2	2

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0.01	-9999	-0.22	1	1
BAD/BCL-XL/YWHAZ	0.027	0.007	-9999	-10000	0	0
CDKN1B	0.021	0.041	-9999	-0.23	1	1
CDKN1A	0.029	0.009	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.011	0	-9999	-10000	0	0
FOXO3	0.029	0.004	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
BAD	0.011	0	-9999	-10000	0	0
AKT3	-0.095	0.14	-9999	-0.28	204	204
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.029	0.013	-9999	-10000	0	0
AKT1/ASK1	0.027	0.015	-9999	-10000	0	0
BAD/YWHAZ	0.022	0	-9999	-10000	0	0
RICTOR	0.009	0.025	-9999	-0.41	2	2
RAF1	0.011	0	-9999	-10000	0	0
JNK cascade	-0.026	0.014	-9999	-10000	0	0
TSC1	0.029	0.009	-9999	-10000	0	0
YWHAZ	0.011	0	-9999	-10000	0	0
AKT1/RAF1	0.03	0.004	-9999	-10000	0	0
EP300	0.011	0	-9999	-10000	0	0
mol:GDP	0.024	0.004	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.029	0.004	-9999	-10000	0	0
YWHAQ	0.011	0	-9999	-10000	0	0
TBC1D4	0.017	0.021	-9999	-0.22	4	4
MAP3K5	0.009	0.031	-9999	-0.41	3	3
MAPKAP1	0.011	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.011	0.015	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0
AKT1S1	0.029	0.004	-9999	-10000	0	0
CASP9	0.029	0.004	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.027	0.039	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.022	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
AKT2/p21CIP1	0.033	0.009	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.002	-9999	-10000	0	0
CHUK	0.029	0.004	-9999	-10000	0	0
BAD/BCL-XL	0.04	0.007	-9999	-10000	0	0
mTORC2	0.013	0.014	-9999	-0.21	2	2
AKT2	0.014	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.022	0.018	-9999	-10000	0	0
PDPK1	0.011	0	-9999	-10000	0	0
MDM2	0.029	0.004	-9999	-10000	0	0
MAPKKK cascade	-0.029	0.004	-9999	-10000	0	0
MDM2/Cbp/p300	0.039	0.012	-9999	-10000	0	0
TSC1/TSC2	0.034	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.012	-9999	-10000	0	0
glucose import	-0.086	0.11	-9999	-0.2	268	268
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.004	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.086	0.11	-9999	-0.2	268	268
GSK3A	0.029	0.004	-9999	-10000	0	0
FOXO1	0.028	0.015	-9999	-10000	0	0
GSK3B	0.029	0.004	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	401	401
G1/S transition of mitotic cell cycle	0.034	0.003	-9999	-10000	0	0
p27Kip1/14-3-3 family	-0.002	0.025	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
KPNA1	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
RHEB	0.011	0	-9999	-10000	0	0
CREBBP	0.009	0.025	-9999	-0.41	2	2

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.02	0.18	1	-10000	0	1
AES	0.011	0.017	0.16	1	-10000	0	1
FBXW11	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.015	0.018	-10000	0	-0.28	2	2
SMAD4	0.01	0.018	-10000	0	-0.41	1	1
DKK2	-0.015	0.1	-10000	0	-0.4	34	34
TLE1	0.011	0.024	0.16	1	-0.41	1	2
MACF1	0.011	0	-10000	0	-10000	0	0
CTNNB1	0.041	0.047	0.21	6	-10000	0	6
WIF1	-0.097	0.16	-10000	0	-0.35	163	163
beta catenin/RanBP3	0.02	0.092	0.36	35	-10000	0	35
KREMEN2	-0.021	0.099	-10000	0	-0.33	51	51
DKK1	-0.065	0.14	-10000	0	-0.33	119	119
beta catenin/beta TrCP1	0.045	0.044	0.2	6	-10000	0	6
FZD1	0.01	0.026	-10000	0	-0.41	2	2
AXIN2	-0.052	0.29	-10000	0	-1.3	27	27
AXIN1	0.011	0	-10000	0	-10000	0	0
RAN	0.011	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.014	0.023	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.05	0.055	0.22	1	-0.32	5	6
Axin1/APC/GSK3	0.018	0.031	0.18	2	-10000	0	2
Axin1/APC/GSK3/beta catenin/Macf1	0.044	0.026	-10000	0	-10000	0	0
HNF1A	0.006	0.045	0.16	1	-0.33	8	9
CTBP1	0.011	0.018	0.17	1	-10000	0	1
MYC	-0.017	0.18	-10000	0	-1.3	10	10
RANBP3	0.011	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.011	0.083	-10000	0	-0.25	35	35
NKD1	-0.02	0.1	-10000	0	-0.34	48	48
TCF4	-0.004	0.08	0.16	1	-0.4	20	21
TCF3	0.011	0.017	0.16	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.024	0.026	-10000	0	-0.2	2	2
Ran/GTP	0.008	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.02	0.11	0.44	29	-0.4	2	31
LEF1	0.007	0.044	0.16	1	-0.38	6	7
DVL1	0.03	0.019	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.047	0.076	-10000	0	-0.34	10	10
DKK1/LRP6/Kremen 2	-0.039	0.096	-10000	0	-0.18	163	163
LRP6	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.02	0.18	1	-10000	0	1
NLK	0.011	0.003	-10000	0	-10000	0	0
CCND1	0.002	0.057	-10000	0	-0.51	1	1
WNT1	0.004	0.041	-10000	0	-0.33	8	8
GSK3A	0.011	0	-10000	0	-10000	0	0
GSK3B	0.011	0	-10000	0	-10000	0	0
FRAT1	0.011	0	-10000	0	-10000	0	0
PPP2R5D	0.031	0.047	0.17	45	-10000	0	45
APC	0.028	0.023	-10000	0	-0.18	1	1
WNT1/LRP6/FZD1	0.038	0.058	0.2	34	-0.2	2	36
CREBBP	0.01	0.03	0.16	1	-0.39	2	3

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.015	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.011	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.032	0.11	-9999	-0.33	69	69
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0.018	-9999	-0.41	1	1
RAC1-CDC42/GTP/PAK family	-0.008	0.069	-9999	-0.18	80	80
response to UV	0	0	-9999	-10000	0	0
YES1	0.011	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.011	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
MAP3K12	0.008	0.036	-9999	-0.41	4	4
FGR	0.002	0.059	-9999	-0.41	11	11
p38 alpha/TAB1	-0.003	0.016	-9999	-0.21	1	1
PRKG1	-0.18	0.21	-9999	-0.41	241	241
DUSP8	0.007	0.04	-9999	-0.41	5	5
PGK/cGMP/p38 alpha	-0.067	0.076	-9999	-0.22	23	23
apoptosis	-0.003	0.015	-9999	-0.2	1	1
RAL/GTP	0.015	0	-9999	-10000	0	0
LYN	0.011	0	-9999	-10000	0	0
DUSP1	-0.09	0.18	-9999	-0.41	130	130
PAK1	0.011	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.028	0	-9999	-10000	0	0
TRAF6	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.011	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.015	0	-9999	-10000	0	0
MAPK11	0.032	0.036	-9999	-10000	0	0
BLK	-0.015	0.087	-9999	-0.33	39	39
HCK	0.007	0.038	-9999	-0.33	7	7
MAP2K3	0.011	0	-9999	-10000	0	0
DUSP16	0.011	0	-9999	-10000	0	0
DUSP10	0.011	0	-9999	-10000	0	0
TRAF6/MEKK3	0.014	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.035	0.028	-9999	-0.23	1	1
positive regulation of innate immune response	0.039	0.039	-9999	-10000	0	0
LCK	0.008	0.034	-9999	-0.34	5	5
p38alpha-beta/MKP7	0.043	0.038	-9999	-10000	0	0
p38alpha-beta/MKP5	0.043	0.038	-9999	-10000	0	0
PGK/cGMP	-0.12	0.15	-9999	-0.29	241	241
PAK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.018	0.074	-9999	-0.26	9	9
CDC42	0.011	0	-9999	-10000	0	0
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
PAK3	-0.054	0.15	-9999	-0.41	80	80

×

BARD1 signaling events

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
BARD1/CSTF1	0.01	0.042	-10000	0	-0.28	11	11
ATM	0.011	0	-10000	0	-10000	0	0
UBE2D3	0.011	0	-10000	0	-10000	0	0
PRKDC	0.011	0	-10000	0	-10000	0	0
ATR	0.011	0	-10000	0	-10000	0	0
UBE2L3	0.011	0	-10000	0	-10000	0	0
FANCD2	0.02	0.007	-10000	0	-10000	0	0
protein ubiquitination	-0.057	0.07	-10000	0	-0.33	5	5
XRCC5	0.011	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
M/R/N Complex	0.022	0	-10000	0	-10000	0	0
MRE11A	0.011	0	-10000	0	-10000	0	0
DNA-PK	0.022	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.019	0.029	-10000	0	-10000	0	0
FANCF	0.009	0.025	-10000	0	-0.41	2	2
BRCA1	0.011	0	-10000	0	-10000	0	0
CCNE1	-0.13	0.17	-10000	0	-0.33	220	220
CDK2/Cyclin E1	-0.078	0.11	-10000	0	-0.22	220	220
FANCG	0.011	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.01	0.042	-10000	0	-0.28	11	11
FANCE	0.011	0	-10000	0	-10000	0	0
FANCC	0.011	0	-10000	0	-10000	0	0
NBN	0.011	0	-10000	0	-10000	0	0
FANCA	-0.072	0.15	-10000	0	-0.33	133	133
DNA repair	-0.015	0.087	-10000	0	-0.31	7	7
BRCA1/BARD1/ubiquitin	0.01	0.042	-10000	0	-0.28	11	11
BARD1/DNA-PK	0.024	0.032	-10000	0	-0.2	11	11
FANCL	0.011	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.01	0.042	0.28	11	-10000	0	11
BRCA1/BARD1/CTIP/M/R/N Complex	0.028	0.031	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0.017	0.035	-10000	0	-0.23	11	11
BRCA1/BARD1/P53	0.023	0.033	-10000	0	-0.2	12	12
BARD1/CSTF1/BRCA1	0.017	0.035	-10000	0	-0.23	11	11
BRCA1/BACH1	0.011	0	-10000	0	-10000	0	0
BARD1	0.002	0.059	-10000	0	-0.41	11	11
PCNA	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.017	0.035	-10000	0	-0.23	11	11
BRCA1/BARD1/UbcH7	0.017	0.035	-10000	0	-0.23	11	11
BRCA1/BARD1/RAD51/PCNA	-0.029	0.089	-10000	0	-0.29	11	11
BARD1/DNA-PK/P53	0.028	0.031	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.01	0.042	-10000	0	-0.28	11	11
BRCA1/BARD1/CTIP	0.023	0.032	-10000	0	-0.2	11	11
FA complex	0.013	0.036	-10000	0	-0.24	1	1
BARD1/EWS	0.01	0.042	-10000	0	-0.28	11	11
RBBP8	0.018	0	-10000	0	-10000	0	0
TP53	0.01	0.018	-10000	0	-0.41	1	1
TOPBP1	0.011	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.022	0.033	0.2	12	-10000	0	12
BRCA1/BARD1	-0.038	0.086	-10000	0	-0.33	5	5
CSTF1	0.011	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.002	0.042	-10000	0	-0.29	11	11
CDK2	0.011	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.091	0.16	-10000	0	-0.33	164	164
RAD50	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.01	0.042	-10000	0	-0.28	11	11
EWSR1	0.011	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.008	0.072	-10000	0	-0.28	35	35
PRKCZ	0.01	0.023	-10000	0	-0.37	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.003	0.022	-10000	0	-0.23	4	4
IRAK/TOLLIP	0.009	0.054	-10000	0	-0.2	35	35
IKBKB	0.011	0	-10000	0	-10000	0	0
IKBKG	0.011	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.016	0.086	-10000	0	-0.24	67	67
IL1A	-0.012	0.083	-10000	0	-0.33	35	35
IL1B	0.015	0.035	-10000	0	-0.33	5	5
IRAK/TRAF6/p62/Atypical PKCs	0.01	0.048	-10000	0	-0.34	1	1
IL1R2	-0.013	0.089	-10000	0	-0.34	38	38
IL1R1	0.003	0.057	-10000	0	-0.41	10	10
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.025	0.057	0.18	22	-0.25	11	33
TOLLIP	0.011	0	-10000	0	-10000	0	0
TICAM2	0.004	0.051	-10000	0	-0.41	8	8
MAP3K3	0.011	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.007	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.04	0.043	-10000	0	-10000	0	0
JUN	0.001	0.07	-10000	0	-0.28	10	10
MAP3K7	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.028	0.05	-10000	0	-0.42	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88	0.011	0.057	-10000	0	-0.23	12	12
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.017	0.053	-10000	0	-0.21	12	12
IL1 beta fragment/IL1R1/IL1RAP	0.019	0.045	-10000	0	-0.22	17	17
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	-0.002	0.07	-10000	0	-0.29	8	8
IRAK1	0.002	0.06	-10000	0	-0.23	35	35
IL1RN/IL1R1	-0.023	0.091	-10000	0	-0.23	87	87
IRAK4	0.011	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
PI3K	0.013	0.031	-10000	0	-0.28	6	6
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.026	0.041	-10000	0	-0.21	13	13
CHUK	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.019	0.045	-10000	0	-0.22	17	17
IL1 beta/IL1R2	0.005	0.058	-10000	0	-0.19	43	43
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.011	0.041	-10000	0	-0.16	35	35
NF kappa B1 p50/RelA	-0.007	0.039	-10000	0	-0.38	3	3
IRAK3	-0.007	0.085	-10000	0	-0.41	23	23
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.027	0.049	-10000	0	-0.36	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.019	0.041	-10000	0	-0.22	12	12
IL1 alpha/IL1R1/IL1RAP	0.003	0.063	-10000	0	-0.2	46	46
RELA	0.011	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.011	0	-10000	0	-10000	0	0
MYD88	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.016	0.051	-10000	0	-0.18	35	35
IL1RAP	0.009	0.031	-10000	0	-0.41	3	3
UBE2N	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.048	-10000	0	-0.3	6	6
CASP1	0.009	0.025	-10000	0	-0.41	2	2
IL1RN/IL1R2	-0.034	0.1	-10000	0	-0.24	107	107
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.026	0.043	-10000	0	-0.2	17	17
TMEM189-UBE2V1	-0.023	0.1	-10000	0	-0.41	35	35
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.017	0.059	-10000	0	-0.33	10	10
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
IL1RN	-0.038	0.12	-10000	0	-0.33	79	79
TRAF6/TAK1/TAB1/TAB2	-0.011	0.043	-10000	0	-0.18	35	35
MAP2K6	-0.006	0.07	-10000	0	-0.19	35	35

×

Regulation of Telomerase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.13	0.12	-9999	-0.43	6	6
RAD9A	0.011	0	-9999	-10000	0	0
AP1	-0.081	0.14	-9999	-0.29	168	168
IFNAR2	0.007	0.019	-9999	-0.41	1	1
AKT1	-0.012	0.058	-9999	-0.18	22	22
ER alpha/Oestrogen	-0.028	0.094	-9999	-0.29	62	62
NFX1/SIN3/HDAC complex	0.032	0.016	-9999	-10000	0	0
EGF	-0.006	0.073	-9999	-0.34	25	25
SMG5	0.011	0	-9999	-10000	0	0
SMG6	0.011	0	-9999	-10000	0	0
SP3/HDAC2	0.012	0.009	-9999	-10000	0	0
TERT/c-Abl	-0.11	0.11	-9999	-0.43	7	7
SAP18	0.011	0.001	-9999	-10000	0	0
MRN complex	0.022	0	-9999	-10000	0	0
WT1	-0.3	0.18	-9999	-0.41	402	402
WRN	0.011	0	-9999	-10000	0	0
SP1	0.009	0.006	-9999	-10000	0	0
SP3	0.01	0.002	-9999	-10000	0	0
TERF2IP	0.011	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.1	0.09	-9999	-0.39	3	3
Mad/Max	0.012	0.009	-9999	-10000	0	0
TERT	-0.13	0.12	-9999	-0.45	5	5
CCND1	-0.11	0.11	-9999	-0.48	1	1
MAX	0.01	0.002	-9999	-10000	0	0
RBBP7	0.011	0.001	-9999	-10000	0	0
RBBP4	0.008	0.031	-9999	-0.41	3	3
TERF2	0.01	0	-9999	-10000	0	0
PTGES3	0.011	0	-9999	-10000	0	0
SIN3A	0.011	0.001	-9999	-10000	0	0
Telomerase/911	0.009	0.021	-9999	-10000	0	0
CDKN1B	-0.015	0.12	-9999	-0.5	23	23
RAD1	0.011	0	-9999	-10000	0	0
XRCC5	0.011	0	-9999	-10000	0	0
XRCC6	0.011	0	-9999	-10000	0	0
SAP30	0.011	0.001	-9999	-10000	0	0
TRF2/PARP2	0.016	0	-9999	-10000	0	0
UBE3A	0.01	0.002	-9999	-10000	0	0
JUN	0.005	0.048	-9999	-0.41	7	7
E6	-0.001	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.005	-9999	-10000	0	0
FOS	-0.12	0.19	-9999	-0.41	167	167
IFN-gamma/IRF1	-0.02	0.086	-9999	-0.22	83	83
PARP2	0.011	0	-9999	-10000	0	0
BLM	-0.026	0.11	-9999	-0.33	60	60
Telomerase	-0.013	0.036	-9999	-10000	0	0
IRF1	0.008	0.033	-9999	-10000	0	0
ESR1	-0.037	0.13	-9999	-0.41	62	62
KU/TER	0.016	0	-9999	-10000	0	0
ATM/TRF2	0.017	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.037	0.015	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.038	0.015	-9999	-10000	0	0
HDAC1	0.011	0.001	-9999	-10000	0	0
HDAC2	0.008	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.016	0.029	-9999	-0.28	5	5
ABL1	0.009	0.025	-9999	-0.41	2	2
MXD1	0.01	0.002	-9999	-10000	0	0
MRE11A	0.011	0	-9999	-10000	0	0
HUS1	0.011	0	-9999	-10000	0	0
RPS6KB1	0.011	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.096	0.096	-9999	-0.4	2	2
NR2F2	-0.008	0.09	-9999	-0.41	26	26
MAPK3	0.003	0.041	-9999	-0.22	18	18
MAPK1	0.003	0.041	-9999	-0.22	18	18
TGFB1/TGF beta receptor Type II	0.011	0.018	-9999	-0.41	1	1
NFKB1	0.01	0.018	-9999	-0.41	1	1
HNRNPC	0.011	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.011	0	-9999	-10000	0	0
EGFR	0	0.066	-9999	-0.41	14	14
mol:Oestrogen	-0.001	0.001	-9999	-10000	0	0
EGF/EGFR	-0.007	0.068	-9999	-0.25	38	38
MYC	0.002	0.057	-9999	-0.41	10	10
IL2	-0.009	0.06	-9999	-0.33	18	18
KU	0.016	0	-9999	-10000	0	0
RAD50	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
TGFB1	0.011	0.018	-9999	-0.41	1	1
TRF2/BLM	-0.007	0.067	-9999	-0.2	60	60
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.11	-9999	-0.42	4	4
SP1/HDAC2	0.014	0.01	-9999	-10000	0	0
PINX1	0.011	0	-9999	-10000	0	0
Telomerase/EST1A	-0.1	0.09	-9999	-0.39	3	3
Smad3/Myc	0.016	0.043	-9999	-0.24	14	14
911 complex	0.022	0	-9999	-10000	0	0
IFNG	-0.032	0.11	-9999	-0.32	60	60
Telomerase/PinX1	-0.1	0.09	-9999	-0.39	3	3
Telomerase/AKT1/mTOR/p70S6K	-0.014	0.04	-9999	-10000	0	0
SIN3B	0.011	0.001	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
Telomerase/EST1B	-0.1	0.09	-9999	-0.39	3	3
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.032	0	-9999	-10000	0	0
TRF2/WRN	0.016	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.1	0.09	-9999	-0.39	3	3
E2F1	-0.055	0.13	-9999	-0.33	102	102
ZNFX1	0.011	0.001	-9999	-10000	0	0
PIF1	-0.075	0.15	-9999	-0.33	138	138
NCL	0.011	0	-9999	-10000	0	0
DKC1	0.011	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.023	0.076	-10000	0	-0.32	9	9
TBX21	0.004	0.25	-10000	0	-0.99	20	20
B2M	0.012	0.005	-10000	0	-10000	0	0
TYK2	0.014	0.016	-10000	0	-10000	0	0
IL12RB1	0.002	0.071	-10000	0	-0.37	18	18
GADD45B	0.037	0.17	-10000	0	-0.65	15	15
IL12RB2	-0.005	0.081	-10000	0	-0.33	30	30
GADD45G	0.015	0.25	-10000	0	-0.99	22	22
natural killer cell activation	0.003	0.016	-10000	0	-10000	0	0
RELB	0.011	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
IL18	0.009	0.044	-10000	0	-0.33	9	9
IL2RA	-0.002	0.066	-10000	0	-0.33	21	21
IFNG	-0.029	0.11	-10000	0	-0.33	60	60
STAT3 (dimer)	0.027	0.19	-10000	0	-0.64	20	20
HLA-DRB5	-0.005	0.067	-10000	0	-0.38	16	16
FASLG	0.008	0.23	-10000	0	-0.94	17	17
NF kappa B2 p52/RelB	-0.064	0.17	-10000	0	-0.69	26	26
CD4	0.006	0.017	-10000	0	-0.34	1	1
SOCS1	0.01	0.018	-10000	0	-0.41	1	1
EntrezGene:6955	-0.006	0.014	-10000	0	-10000	0	0
CD3D	-0.008	0.073	-10000	0	-0.37	21	21
CD3E	-0.002	0.064	-10000	0	-0.39	14	14
CD3G	0	0.047	-10000	0	-0.35	9	9
IL12Rbeta2/JAK2	0.005	0.072	-10000	0	-0.24	39	39
CCL3	0.012	0.22	-10000	0	-0.9	14	14
CCL4	0.009	0.24	-10000	0	-0.98	16	16
HLA-A	0.011	0.015	-10000	0	-0.33	1	1
IL18/IL18R	0.043	0.054	-10000	0	-0.22	16	16
NOS2	0.017	0.23	-10000	0	-1	17	17
IL12/IL12R/TYK2/JAK2/SPHK2	0.023	0.073	-10000	0	-0.29	9	9
IL1R1	0.002	0.26	-10000	0	-1.1	19	19
IL4	0.001	0.017	-10000	0	-10000	0	0
JAK2	0.007	0.057	-10000	0	-0.42	9	9
EntrezGene:6957	-0.005	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.001	0.12	-10000	0	-0.58	17	17
RAB7A	0.043	0.18	-10000	0	-0.69	10	10
lysosomal transport	0.044	0.17	-10000	0	-0.63	12	12
FOS	-0.3	0.56	-10000	0	-1.1	170	170
STAT4 (dimer)	0.04	0.2	-10000	0	-0.66	21	21
STAT5A (dimer)	-0.073	0.18	-10000	0	-0.7	29	29
GZMA	-0.004	0.26	-10000	0	-1	23	23
GZMB	0.002	0.23	-10000	0	-0.97	15	15
HLX	0.011	0	-10000	0	-10000	0	0
LCK	0.019	0.23	-10000	0	-0.79	24	24
TCR/CD3/MHC II/CD4	-0.042	0.12	-10000	0	-0.33	29	29
IL2/IL2R	0.008	0.062	-10000	0	-0.3	14	14
MAPK14	0.036	0.2	-10000	0	-0.68	24	24
CCR5	0.029	0.2	-10000	0	-0.83	15	15
IL1B	0.011	0.042	-10000	0	-0.44	4	4
STAT6	0.024	0.077	0.2	1	-0.25	13	14
STAT4	0.01	0.018	-10000	0	-0.41	1	1
STAT3	0.011	0	-10000	0	-10000	0	0
STAT1	0.01	0.021	-10000	0	-0.33	2	2
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
NFKB2	0.011	0	-10000	0	-10000	0	0
IL12B	0.01	0.021	-10000	0	-0.31	1	1
CD8A	0.002	0.064	-10000	0	-0.39	14	14
CD8B	-0.01	0.087	-10000	0	-0.35	33	33
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.023	0.075	0.32	9	-10000	0	9
IL2RB	0.01	0.018	-10000	0	-0.41	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.19	-10000	0	-0.61	21	21
IL2RG	0.005	0.047	-10000	0	-0.36	9	9
IL12	0.014	0.049	-10000	0	-0.23	16	16
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
CD247	0.006	0.03	-10000	0	-0.38	3	3
IL2	-0.007	0.06	-10000	0	-0.33	18	18
SPHK2	0.011	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.003	0.061	-10000	0	-0.34	15	15
IL12/IL12R/TYK2/JAK2	0.019	0.24	-10000	0	-0.81	26	26
MAP2K3	0.03	0.2	-10000	0	-0.66	25	25
RIPK2	0.011	0	-10000	0	-10000	0	0
MAP2K6	0.032	0.2	-10000	0	-0.66	24	24
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.004	0.028	-10000	0	-0.42	2	2
IL18RAP	0.01	0.045	-10000	0	-0.38	7	7
IL12Rbeta1/TYK2	0.012	0.055	-10000	0	-0.26	18	18
EOMES	-0.009	0.14	-10000	0	-1.2	7	7
STAT1 (dimer)	0.029	0.18	-10000	0	-0.63	20	20
T cell proliferation	0.038	0.16	-10000	0	-0.51	21	21
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.012	0.037	-10000	0	-0.41	4	4
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.039	0.13	-10000	0	-0.55	23	23
ATF2	0.039	0.19	-10000	0	-0.62	25	25

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.027	0.025	-9999	-10000	0	0
PLK1	-0.087	0.18	-9999	-0.53	55	55
CDKN1B	0.003	0.14	-9999	-0.45	26	26
FOXO3	-0.048	0.18	-9999	-0.5	58	58
KAT2B	-0.002	0.057	-9999	-0.42	9	9
FOXO1/SIRT1	0.022	0.03	-9999	-10000	0	0
CAT	-0.038	0.17	-9999	-0.54	22	22
CTNNB1	0.011	0	-9999	-10000	0	0
AKT1	0.007	0.016	-9999	-10000	0	0
FOXO1	0.026	0.026	-9999	-0.22	5	5
MAPK10	-0.019	0.09	-9999	-0.19	116	116
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.038	0.076	-9999	-0.29	5	5
response to oxidative stress	-0.005	0.018	-9999	-10000	0	0
FOXO3A/SIRT1	-0.072	0.15	-9999	-0.47	59	59
XPO1	0.012	0	-9999	-10000	0	0
EP300	0.012	0.001	-9999	-10000	0	0
BCL2L11	0.011	0.025	-9999	-10000	0	0
FOXO1/SKP2	0.029	0.023	-9999	-0.21	2	2
mol:GDP	-0.005	0.018	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
GADD45A	0.012	0.096	-9999	-0.42	2	2
YWHAQ	0.011	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.033	0.017	-9999	-10000	0	0
MST1	0.001	0.042	-9999	-0.34	7	7
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.011	0.021	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
MAPK8	0.024	0.024	-9999	-0.19	6	6
MAPK9	0.026	0.008	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
YWHAZ	0.011	0	-9999	-10000	0	0
SIRT1	0.009	0.026	-9999	-0.41	2	2
SOD2	0.02	0.12	-9999	-0.4	7	7
RBL2	-0.013	0.15	-9999	-0.8	5	5
RAL/GDP	0.016	0.012	-9999	-10000	0	0
CHUK	0.005	0.016	-9999	-10000	0	0
Ran/GTP	0.011	0.001	-9999	-10000	0	0
CSNK1G2	0.011	0	-9999	-10000	0	0
RAL/GTP	0.022	0.012	-9999	-10000	0	0
CSNK1G1	0.011	0	-9999	-10000	0	0
FASLG	0	0.12	-9999	-1.3	4	4
SKP2	0.011	0	-9999	-10000	0	0
USP7	0.012	0	-9999	-10000	0	0
IKBKB	0.005	0.016	-9999	-10000	0	0
CCNB1	-0.049	0.18	-9999	-0.61	21	21
FOXO1-3a-4/beta catenin	0.035	0.11	-9999	-0.37	7	7
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.023	-9999	-0.2	2	2
CSNK1A1	0.011	0	-9999	-10000	0	0
SGK1	0.004	0.031	-9999	-0.44	2	2
CSNK1G3	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.02	0.002	-9999	-10000	0	0
ZFAND5	0.042	0.067	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	401	401
CDK2	0.013	0.002	-9999	-10000	0	0
FOXO3A/14-3-3	0.004	0.035	-9999	-10000	0	0
CREBBP	0.011	0.026	-9999	-0.41	2	2
FBXO32	-0.13	0.4	-9999	-1.2	69	69
BCL6	-0.011	0.14	-9999	-0.6	7	7
RALB	0.012	0	-9999	-10000	0	0
RALA	0.012	0	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.021	0.02	-9999	-0.17	6	6
SNTA1	0.011	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.021	0.02	-9999	-0.17	6	6
MAPK12	-0.009	0.073	-9999	-0.21	27	27
CCND1	0.003	0.033	-9999	-10000	0	0
p38 gamma/SNTA1	-0.003	0.068	-9999	-0.33	1	1
MAP2K3	0.011	0	-9999	-10000	0	0
PKN1	0.011	0	-9999	-10000	0	0
G2/M transition checkpoint	-0.009	0.072	-9999	-0.21	27	27
MAP2K6	-0.017	0.08	-9999	-0.19	94	94
MAPT	0.002	0.061	-9999	-0.28	20	20
MAPK13	0.016	0.025	-9999	-0.22	6	6
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0	0.062	-9999	-0.28	26	26

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.012	0.066	-10000	0	-0.35	15	15
FYN	0.034	0.099	-10000	0	-0.44	16	16
LAT/GRAP2/SLP76	-0.012	0.081	-10000	0	-0.39	18	18
IKBKB	0.011	0	-10000	0	-10000	0	0
AKT1	0.039	0.076	-10000	0	-0.32	17	17
B2M	0.012	0.002	-10000	0	-10000	0	0
IKBKG	-0.004	0.018	-10000	0	-0.12	9	9
MAP3K8	0.009	0.031	-10000	0	-0.41	3	3
mol:Ca2+	-0.006	0.017	-10000	0	-0.081	19	19
integrin-mediated signaling pathway	0.015	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.038	0.1	-10000	0	-0.46	17	17
TRPV6	-0.045	0.13	-10000	0	-0.4	61	61
CD28	0.01	0.021	-10000	0	-0.33	2	2
SHC1	0.033	0.095	-10000	0	-0.44	15	15
receptor internalization	0.028	0.088	-10000	0	-0.44	14	14
PRF1	0.022	0.13	-10000	0	-0.84	9	9
KRAS	0.01	0.015	-10000	0	-0.33	1	1
GRB2	0.011	0	-10000	0	-10000	0	0
COT/AKT1	0.04	0.063	-10000	0	-0.27	15	15
LAT	0.034	0.095	-10000	0	-0.44	15	15
EntrezGene:6955	0.001	0.002	-10000	0	-10000	0	0
CD3D	-0.002	0.072	-10000	0	-0.36	21	21
CD3E	0.002	0.064	-10000	0	-0.39	14	14
CD3G	0.006	0.047	-10000	0	-0.35	9	9
RASGRP2	-0.01	0.058	-10000	0	-0.16	74	74
RASGRP1	0.041	0.084	-10000	0	-0.36	16	16
HLA-A	0.012	0.015	-10000	0	-0.33	1	1
RASSF5	0.011	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.025	0.035	-10000	0	-0.11	12	12
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.008	0.032	-10000	0	-0.18	13	13
PRKCA	-0.006	0.046	-10000	0	-0.21	16	16
GRAP2	-0.002	0.073	-10000	0	-0.41	17	17
mol:IP3	0.004	0.081	0.18	51	-0.32	14	65
EntrezGene:6957	0.001	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.019	0.082	-10000	0	-0.41	14	14
ORAI1	0.027	0.075	0.24	61	-10000	0	61
CSK	0.032	0.097	-10000	0	-0.43	16	16
B7 family/CD28	0.032	0.097	-10000	0	-0.43	16	16
CHUK	0.011	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.028	0.11	-10000	0	-0.48	16	16
PTPN6	0.03	0.096	-10000	0	-0.43	16	16
VAV1	0.032	0.1	-10000	0	-0.46	15	15
Monovalent TCR/CD3	0.012	0.063	-10000	0	-0.29	19	19
CBL	0.011	0	-10000	0	-10000	0	0
LCK	0.031	0.1	-10000	0	-0.46	16	16
PAG1	0.031	0.099	-10000	0	-0.44	17	17
RAP1A	0.011	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.028	0.11	-10000	0	-0.48	16	16
CD80	-0.008	0.077	-10000	0	-0.33	30	30
CD86	0.01	0.021	-10000	0	-0.33	2	2
PDK1/CARD11/BCL10/MALT1	-0.01	0.039	-10000	0	-0.22	13	13
HRAS	0.011	0	-10000	0	-10000	0	0
GO:0035030	0.03	0.084	-10000	0	-0.37	16	16
CD8A	0.002	0.064	-10000	0	-0.39	14	14
CD8B	-0.009	0.087	-10000	0	-0.35	33	33
PTPRC	0.003	0.059	-10000	0	-0.4	11	11
PDK1/PKC theta	0.041	0.095	-10000	0	-0.41	16	16
CSK/PAG1	0.034	0.097	-10000	0	-0.42	17	17
SOS1	0.011	0	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.011	-10000	0	-0.21	1	1
GRAP2/SLP76	-0.013	0.093	-10000	0	-0.45	18	18
STIM1	0.014	0.036	-10000	0	-10000	0	0
RAS family/GTP	0.04	0.036	-10000	0	-0.16	6	6
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.028	0.092	-10000	0	-0.46	14	14
mol:DAG	-0.005	0.058	-10000	0	-0.3	14	14
RAP1A/GDP	0.012	0.015	-10000	0	-0.057	6	6
PLCG1	0.011	0	-10000	0	-10000	0	0
CD247	0.01	0.03	-10000	0	-0.39	3	3
cytotoxic T cell degranulation	0.023	0.12	-10000	0	-0.79	9	9
RAP1A/GTP	-0.008	0.019	-10000	0	-0.057	74	74
mol:PI-3-4-5-P3	0.038	0.088	-10000	0	-0.38	17	17
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.002	0.095	0.2	49	-0.41	14	63
NRAS	0.011	0	-10000	0	-10000	0	0
ZAP70	0	0.063	-10000	0	-0.34	18	18
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.011	0.079	-10000	0	-0.41	15	15
MALT1	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.003	0.079	-10000	0	-0.26	43	43
CARD11	0.001	0.059	-10000	0	-0.34	15	15
PRKCB	-0.007	0.057	-10000	0	-0.27	19	19
PRKCE	-0.003	0.041	-10000	0	-0.21	14	14
PRKCQ	0.035	0.1	-10000	0	-0.43	19	19
LCP2	0.01	0.015	-10000	0	-0.33	1	1
BCL10	0.011	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.038	0.067	-10000	0	-0.28	17	17
IKK complex	0.03	0.036	-10000	0	-0.097	15	15
RAS family/GDP	-0.001	0.005	-10000	0	-10000	0	0
MAP3K14	0.039	0.051	-10000	0	-0.21	13	13
PDPK1	0.04	0.073	-10000	0	-0.31	16	16
TCR/CD3/MHC I/CD8/Fyn	0.022	0.12	-10000	0	-0.49	20	20

×

Signaling events mediated by PRL

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.13	0.17	-9999	-0.33	220	220
mol:Halofuginone	0.004	0	-9999	-10000	0	0
ITGA1	0.009	0.031	-9999	-0.41	3	3
CDKN1A	0.012	0.04	-9999	-0.36	1	1
PRL-3/alpha Tubulin	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.042	0.1	-9999	-0.29	79	79
AGT	-0.049	0.15	-9999	-0.4	79	79
CCNA2	-0.029	0.099	-9999	-0.33	20	20
TUBA1B	0.011	0	-9999	-10000	0	0
EGR1	-0.019	0.1	-9999	-0.28	71	71
CDK2/Cyclin E1	-0.041	0.087	-9999	-0.46	1	1
MAPK3	0.018	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.016	0	-9999	-10000	0	0
MAPK1	0.018	0	-9999	-10000	0	0
PTP4A1	0	0.075	-9999	-10000	0	0
PTP4A3	0.011	0	-9999	-10000	0	0
PTP4A2	0.011	0	-9999	-10000	0	0
ITGB1	0.018	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
RAC1	0.013	0.036	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.016	0	-9999	-10000	0	0
PRL-1/ATF-5	0.005	0.071	-9999	-0.33	1	1
RABGGTA	0.011	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	0.013	0.036	-9999	-10000	0	0
RHOA	0.013	0.036	-9999	-10000	0	0
cell motility	0.016	0.039	-9999	-10000	0	0
PRL-1/alpha Tubulin	0.006	0.07	-9999	-10000	0	0
PRL-3/alpha1 Integrin	0.015	0.022	-9999	-0.28	3	3
ROCK1	0.016	0.039	-9999	-10000	0	0
RABGGTB	0.011	0	-9999	-10000	0	0
CDK2	0.011	0	-9999	-10000	0	0
mitosis	0	0.074	-9999	-10000	0	0
ATF5	0.008	0.029	-9999	-0.33	4	4

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0	-9999	-10000	0	0
SPHK1	0.009	0.025	-9999	-0.33	3	3
GNAI2	0.011	0	-9999	-10000	0	0
mol:S1P	0.018	0.006	-9999	-10000	0	0
GNAO1	-0.1	0.18	-9999	-0.41	143	143
mol:Sphinganine-1-P	0.017	0.017	-9999	-0.22	3	3
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.032	0.004	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.016	0	-9999	-10000	0	0
S1PR3	-0.004	0.077	-9999	-0.41	19	19
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0	0.004	-9999	-10000	0	0
S1PR5	0	0.063	-9999	-0.35	17	17
S1PR4	0.009	0.029	-9999	-0.38	3	3
GNAI1	0.005	0.051	-9999	-0.41	8	8
S1P/S1P5/G12	0.021	0.032	-9999	-0.19	4	4
S1P/S1P3/Gq	-0.007	0.1	-9999	-0.25	74	74
S1P/S1P4/Gi	-0.032	0.11	-9999	-0.38	14	14
GNAQ	0.009	0.025	-9999	-0.41	2	2
GNAZ	-0.002	0.073	-9999	-0.41	17	17
GNA14	-0.031	0.13	-9999	-0.41	54	54
GNA15	0.007	0.038	-9999	-0.33	7	7
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
GNA11	0.002	0.062	-9999	-0.41	12	12
ABCC1	0.011	0	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.014	0.051	-10000	0	-0.17	11	11
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.011	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.037	0.048	-10000	0	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.015	0.037	-10000	0	-0.23	11	11
antigen processing and presentation of peptide antigen via MHC class I	-0.031	0.042	-10000	0	-0.24	5	5
CaM/Ca2+	-0.013	0.036	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.018	0.05	-10000	0	-0.24	2	2
AKT1	0.024	0.049	-10000	0	-0.28	2	2
MAP2K1	0.024	0.046	-10000	0	-10000	0	0
MAP3K11	0.017	0.048	-10000	0	-10000	0	0
IFNGR1	0.011	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.18	0.16	-10000	0	-0.33	304	304
Rap1/GTP	-0.009	0.023	-10000	0	-10000	0	0
CRKL/C3G	0.016	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.013	0.055	-10000	0	-0.18	11	11
CEBPB	0.048	0.048	-10000	0	-0.38	2	2
STAT3	0.011	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.018	0.067	-10000	0	-1	1	1
STAT1	0.017	0.05	-10000	0	-0.24	2	2
CALM1	0.011	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.027	0.1	-10000	0	-0.32	60	60
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
STAT1 (dimer)/PIAS1	0.023	0.048	-10000	0	-0.23	2	2
CEBPB/PTGES2/Cbp/p300	-0.003	0.018	-10000	0	-0.24	2	2
mol:Ca2+	0.012	0.05	-10000	0	-0.17	11	11
MAPK3	0.033	0.042	-10000	0	-10000	0	0
STAT1 (dimer)	-0.039	0.056	-10000	0	-0.33	5	5
MAPK1	0.033	0.042	-10000	0	-10000	0	0
JAK2	0.004	0.054	-10000	0	-0.41	9	9
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
JAK1	0.01	0.026	-10000	0	-0.41	2	2
CAMK2D	0.009	0.025	-10000	0	-0.41	2	2
DAPK1	0.046	0.049	-10000	0	-0.58	2	2
SMAD7	0.001	0.041	-10000	0	-0.29	2	2
CBL/CRKL/C3G	0.027	0.044	-10000	0	-10000	0	0
PI3K	-0.014	0.039	-10000	0	-0.31	2	2
IFNG	-0.027	0.1	-10000	0	-0.32	60	60
apoptosis	0.027	0.04	-10000	0	-0.43	2	2
CAMK2G	0.011	0	-10000	0	-10000	0	0
STAT3 (dimer)	0.011	0	-10000	0	-10000	0	0
CAMK2A	-0.22	0.21	-10000	0	-0.41	304	304
CAMK2B	-0.045	0.13	-10000	0	-0.33	89	89
FRAP1	0.023	0.046	-10000	0	-0.27	2	2
PRKCD	0.026	0.049	-10000	0	-0.28	2	2
RAP1B	0.011	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.031	0.042	-10000	0	-0.24	5	5
PTPN2	0.011	0	-10000	0	-10000	0	0
EP300	0.011	0	-10000	0	-10000	0	0
IRF1	0.044	0.043	-10000	0	-0.25	1	1
STAT1 (dimer)/PIASy	0.02	0.048	0.18	1	-0.23	2	3
SOCS1	0.001	0.055	-10000	0	-1.3	1	1
mol:GDP	-0.011	0.029	-10000	0	-10000	0	0
CASP1	0.001	0.04	-10000	0	-0.19	4	4
PTGES2	0.01	0.018	-10000	0	-0.41	1	1
IRF9	0.04	0.019	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.014	0.038	-10000	0	-0.3	2	2
RAP1/GDP	-0.009	0.023	-10000	0	-10000	0	0
CBL	0.017	0.047	-10000	0	-10000	0	0
MAP3K1	0.018	0.048	-10000	0	-10000	0	0
PIAS1	0.011	0	-10000	0	-10000	0	0
PIAS4	0.011	0	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.031	0.042	-10000	0	-0.24	5	5
PTPN11	0.011	0.05	-10000	0	-0.17	11	11
CREBBP	0.01	0.025	-10000	0	-0.41	2	2
RAPGEF1	0.011	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	0.01	0.015	-10000	0	-0.33	1	1
NFATC1	0.034	0.05	-10000	0	-0.25	15	15
NFATC2	0.015	0.049	-10000	0	-0.21	8	8
NFATC3	0.018	0.016	-10000	0	-0.31	1	1
YWHAE	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.016	0.1	-10000	0	-0.36	27	27
Exportin 1/Ran/NUP214	0.021	0.006	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.031	0.08	-10000	0	-0.35	22	22
BCL2/BAX	-0.011	0.086	-10000	0	-0.28	50	50
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.004	-10000	0	-10000	0	0
CaM/Ca2+	0.008	0.004	-10000	0	-10000	0	0
BAX	0.011	0	-10000	0	-10000	0	0
MAPK14	0.011	0.003	-10000	0	-10000	0	0
BAD	0.011	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.01	0.099	-10000	0	-0.38	21	21
Calcineurin A alpha-beta B1/BCL2	-0.028	0.12	-10000	0	-0.41	50	50
FKBP8	0.011	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.01	0.098	0.38	21	-10000	0	21
KPNB1	0.011	0	-10000	0	-10000	0	0
KPNA2	-0.005	0.071	-10000	0	-0.33	25	25
XPO1	0.011	0	-10000	0	-10000	0	0
SFN	-0.24	0.15	-10000	0	-0.33	401	401
MAP3K8	0.008	0.031	-10000	0	-0.41	3	3
NFAT4/CK1 alpha	0.026	0.012	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.025	0.077	-10000	0	-0.32	6	6
CABIN1	-0.017	0.1	-10000	0	-0.36	27	27
CALM1	0.011	0.002	-10000	0	-10000	0	0
RAN	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.011	0	-10000	0	-10000	0	0
CAMK4	0.004	0.05	-10000	0	-0.36	10	10
mol:Ca2+	0	0.004	-10000	0	-10000	0	0
MAPK3	0.011	0	-10000	0	-10000	0	0
YWHAH	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.014	0.022	-10000	0	-0.28	3	3
YWHAB	0.011	0	-10000	0	-10000	0	0
MAPK8	0.006	0.044	-10000	0	-0.41	6	6
MAPK9	0.011	0	-10000	0	-10000	0	0
YWHAG	0.011	0	-10000	0	-10000	0	0
FKBP1A	0.011	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.044	0.048	-10000	0	-0.25	2	2
PRKCH	0.009	0.031	-10000	0	-0.41	3	3
CABIN1/Cbp/p300	0.015	0.019	-10000	0	-0.28	2	2
CASP3	0.011	0.003	-10000	0	-10000	0	0
PIM1	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.002	-10000	0	-10000	0	0
apoptosis	-0.007	0.023	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.02	-10000	0	-10000	0	0
PRKCB	-0.014	0.099	-10000	0	-0.41	32	32
PRKCE	0.011	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.022	0.014	-10000	0	-0.28	1	1
BAD/BCL-XL	0.016	0.01	-10000	0	-0.22	1	1
PRKCD	0.011	0	-10000	0	-10000	0	0
NUP214	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.023	-10000	0	-0.37	2	2
PRKCA	-0.017	0.1	-10000	0	-0.41	36	36
PRKCG	-0.037	0.12	-10000	0	-0.34	74	74
PRKCQ	-0.026	0.12	-10000	0	-0.41	48	48
FKBP38/BCL2	-0.011	0.086	-10000	0	-0.28	50	50
EP300	0.011	0.003	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
NFATc/JNK1	0.036	0.053	-10000	0	-0.23	15	15
CaM/Ca2+/FKBP38	0.015	0.004	-10000	0	-10000	0	0
FKBP12/FK506	0.008	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.011	0.029	-10000	0	-0.2	10	10
NFATc/ERK1	0.039	0.048	-10000	0	-0.28	2	2
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.031	0.08	-10000	0	-0.35	22	22
NR4A1	0.015	0.12	-10000	0	-0.4	36	36
GSK3B	0.011	0.003	-10000	0	-10000	0	0
positive T cell selection	0.018	0.016	-10000	0	-0.31	1	1
NFAT1/CK1 alpha	-0.01	0.028	-10000	0	-0.22	3	3
RCH1/ KPNB1	0.006	0.049	-10000	0	-0.22	25	25
YWHAQ	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0.003	-10000	0	-10000	0	0
AKAP5	0.009	0.031	-10000	0	-0.41	3	3
MEF2D	0.011	0.003	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.011	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.038	0.049	-10000	0	-0.29	2	2
CREBBP	0.009	0.026	-10000	0	-0.41	2	2
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.015	0.085	-9999	-0.38	23	23
PDGFB-D/PDGFRB/SLAP	0.004	0.06	-9999	-0.28	24	24
PDGFB-D/PDGFRB/APS/CBL	0.012	0.05	-9999	-0.23	23	23
AKT1	0.035	0.047	-9999	-0.3	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.015	0.091	-9999	-0.41	23	23
PIK3CA	0.01	0.018	-9999	-0.41	1	1
FGR	-0.02	0.1	-9999	-0.37	31	31
mol:Ca2+	0.011	0.096	-9999	-0.44	23	23
MYC	0.022	0.13	-9999	-0.67	13	13
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	0.02	0.047	-9999	-0.21	7	7
LRP1/PDGFRB/PDGFB	0.011	0.054	-9999	-0.24	24	24
GRB10	0.01	0.018	-9999	-0.41	1	1
PTPN11	0.011	0	-9999	-10000	0	0
GO:0007205	0.01	0.097	-9999	-0.45	23	23
PTEN	0.006	0.044	-9999	-0.41	6	6
GRB2	0.011	0	-9999	-10000	0	0
GRB7	-0.011	0.084	-9999	-0.33	34	34
PDGFB-D/PDGFRB/SHP2	0.004	0.06	-9999	-0.28	23	23
PDGFB-D/PDGFRB/GRB10	0.004	0.061	-9999	-0.28	24	24
cell cycle arrest	0.004	0.06	-9999	-0.28	24	24
HRAS	0.011	0	-9999	-10000	0	0
HIF1A	0.039	0.043	-9999	-0.26	2	2
GAB1	0.014	0.093	-9999	-0.41	23	23
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.018	0.086	-9999	-0.37	23	23
PDGFB-D/PDGFRB	0.013	0.052	-9999	-0.23	23	23
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.004	0.06	-9999	-0.28	23	23
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.015	0.072	-9999	-0.34	23	23
positive regulation of MAPKKK cascade	0.004	0.059	-9999	-0.28	23	23
PIK3R1	0.007	0.04	-9999	-0.41	5	5
mol:IP3	0.01	0.098	-9999	-0.45	23	23
E5	0	0.001	-9999	-10000	0	0
CSK	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.01	0.085	-9999	-0.26	53	53
SHB	0.011	0	-9999	-10000	0	0
BLK	-0.011	0.053	-9999	-0.26	23	23
PTPN2	0.011	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.004	0.06	-9999	-0.28	23	23
BCAR1	0.011	0	-9999	-10000	0	0
VAV2	0.017	0.096	-9999	-0.4	23	23
CBL	0.011	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.004	0.06	-9999	-0.28	23	23
LCK	-0.013	0.065	-9999	-0.29	23	23
PDGFRB	-0.006	0.086	-9999	-0.41	23	23
ACP1	0.011	0	-9999	-10000	0	0
HCK	-0.01	0.053	-9999	-0.26	23	23
ABL1	0.015	0.079	-9999	-0.34	23	23
PDGFB-D/PDGFRB/CBL	0.012	0.1	-9999	-0.47	23	23
PTPN1	0.011	0.002	-9999	-10000	0	0
SNX15	0.011	0	-9999	-10000	0	0
STAT3	0.011	0	-9999	-10000	0	0
STAT1	0.01	0.021	-9999	-0.33	2	2
cell proliferation	0.023	0.11	-9999	-0.59	13	13
SLA	0.01	0.015	-9999	-0.33	1	1
actin cytoskeleton reorganization	0.032	0.043	-9999	-0.35	1	1
SRC	-0.01	0.053	-9999	-0.26	23	23
PI3K	-0.01	0.039	-9999	-0.33	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0	0.072	-9999	-0.21	53	53
SH2B2	0.011	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.015	0.094	-9999	-0.42	23	23
LYN	-0.01	0.053	-9999	-0.26	23	23
LRP1	0.009	0.025	-9999	-0.41	2	2
SOS1	0.011	0	-9999	-10000	0	0
STAT5B	0.009	0.025	-9999	-0.41	2	2
STAT5A	0.01	0.018	-9999	-0.41	1	1
NCK1-2/p130 Cas	-0.004	0.039	-9999	-0.37	1	1
SPHK1	0.009	0.025	-9999	-0.33	3	3
EDG1	0.001	0.002	-9999	-10000	0	0
mol:DAG	0.01	0.098	-9999	-0.45	23	23
PLCG1	0.01	0.1	-9999	-0.46	23	23
NHERF/PDGFRB	0.011	0.052	-9999	-0.22	27	27
YES1	-0.011	0.052	-9999	-0.26	23	23
cell migration	0.011	0.052	-9999	-0.22	27	27
SHC/Grb2/SOS1	-0.004	0.036	-9999	-10000	0	0
SLC9A3R2	0.011	0	-9999	-10000	0	0
SLC9A3R1	0.008	0.029	-9999	-0.33	4	4
NHERF1-2/PDGFRB/PTEN	0.015	0.054	-9999	-0.2	28	28
FYN	-0.01	0.053	-9999	-0.26	23	23
DOK1	0.017	0.046	-9999	-0.2	23	23
HRAS/GTP	0.008	0	-9999	-10000	0	0
PDGFB	0.011	0	-9999	-10000	0	0
RAC1	0.023	0.1	-9999	-0.37	33	33
PRKCD	0.018	0.046	-9999	-0.2	23	23
FER	0.018	0.046	-9999	-0.2	23	23
MAPKKK cascade	-0.006	0.034	-9999	-10000	0	0
RASA1	0.016	0.052	-9999	-0.21	27	27
NCK1	0.009	0.025	-9999	-0.41	2	2
NCK2	0.011	0	-9999	-10000	0	0
p62DOK/Csk	0.022	0.042	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.004	0.06	-9999	-0.28	23	23
chemotaxis	0.016	0.077	-9999	-0.34	23	23
STAT1-3-5/STAT1-3-5	-0.008	0.036	-9999	-0.35	1	1
Bovine Papilomavirus E5/PDGFRB	-0.003	0.06	-9999	-0.29	23	23
PTPRJ	0.011	0	-9999	-10000	0	0

×

ErbB4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.007	0.045	-9999	-10000	0	0
epithelial cell differentiation	-0.041	0.076	-9999	-0.33	12	12
ITCH	0.017	0.011	-9999	-10000	0	0
WWP1	0.007	0.042	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
EGFR	0	0.066	-9999	-0.4	14	14
PRL	-0.01	0.083	-9999	-0.39	24	24
neuron projection morphogenesis	0.03	0.051	-9999	-10000	0	0
PTPRZ1	-0.015	0.081	-9999	-0.33	34	34
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.021	0.054	-9999	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.005	0.059	-9999	-0.3	6	6
ADAM17	0.017	0.011	-9999	-10000	0	0
ErbB4/ErbB4	0.003	0.054	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.009	0.058	-9999	-0.28	2	2
NCOR1	0.011	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.011	0.055	-9999	-0.28	6	6
GRIN2B	0.007	0.062	-9999	-0.34	3	3
ErbB4/ErbB2/betacellulin	0.007	0.056	-9999	-0.29	3	3
STAT1	0.01	0.021	-9999	-0.33	2	2
HBEGF	0.011	0	-9999	-10000	0	0
PRLR	-0.075	0.17	-9999	-0.41	111	111
E4ICDs/ETO2	-0.026	0.096	-9999	-0.35	11	11
axon guidance	0.014	0.037	-9999	-10000	0	0
NEDD4	-0.02	0.12	-9999	-0.41	44	44
Prolactin receptor/Prolactin receptor/Prolactin	-0.058	0.13	-9999	-0.29	128	128
CBFA2T3	-0.049	0.15	-9999	-0.41	78	78
ErbB4/ErbB2/HBEGF	0.015	0.042	-9999	-10000	0	0
MAPK3	0.025	0.052	-9999	-10000	0	0
STAT1 (dimer)	0.007	0.047	-9999	-0.28	1	1
MAPK1	0.025	0.052	-9999	-10000	0	0
JAK2	0.004	0.054	-9999	-0.41	9	9
ErbB4/ErbB2/neuregulin 1 beta	0.007	0.061	-9999	-0.29	7	7
NRG1	0.01	0.058	-9999	-0.28	21	21
NRG3	-0.008	0.068	-9999	-0.33	23	23
NRG2	-0.052	0.15	-9999	-0.41	81	81
NRG4	-0.02	0.097	-9999	-0.33	49	49
heart development	0.014	0.037	-9999	-10000	0	0
neural crest cell migration	0.007	0.061	-9999	-0.29	7	7
ERBB2	0.015	0.039	-9999	-0.22	14	14
WWOX/E4ICDs	0.007	0.045	-9999	-10000	0	0
SHC1	0.011	0	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.007	0.077	-9999	-0.34	9	9
apoptosis	0.007	0.037	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.029	0.097	-9999	-0.34	13	13
ErbB4/ErbB2/epiregulin	-0.009	0.068	-9999	-0.3	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.001	0.062	-9999	-0.36	3	3
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.032	0.11	-9999	-0.32	34	34
MDM2	0.009	0.046	-9999	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.008	0.046	-9999	-0.27	6	6
STAT5A	0.018	0.037	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	0.006	0.067	-9999	-0.32	10	10
DLG4	0.008	0.036	-9999	-0.41	4	4
GRB2/SHC	0.016	0	-9999	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.011	0.033	-9999	-10000	0	0
STAT5A (dimer)	-0.043	0.081	-9999	-0.38	8	8
MAP3K7IP2	0	0	-9999	-10000	0	0
STAT5B (dimer)	0.018	0.039	-9999	-0.32	1	1
LRIG1	0.009	0.031	-9999	-0.41	3	3
EREG	-0.034	0.11	-9999	-0.33	70	70
BTC	-0.003	0.075	-9999	-0.41	18	18
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.016	0.035	-9999	-10000	0	0
ERBB4	0.003	0.054	-9999	-10000	0	0
STAT5B	0.009	0.025	-9999	-0.41	2	2
YAP1	-0.001	0.023	-9999	-0.52	1	1
GRB2	0.011	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0	0.067	-9999	-0.3	5	5
glial cell differentiation	0.011	0.033	-9999	-10000	0	0
WWOX	0.011	0	-9999	-10000	0	0
cell proliferation	0.01	0.069	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.069	0.088	-9999	-0.28	1	1
CaM/Ca2+	0.008	0	-9999	-10000	0	0
AKT1	0.011	0	-9999	-10000	0	0
AKT2	0.011	0	-9999	-10000	0	0
STXBP4	0.01	0.018	-9999	-0.41	1	1
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.074	0.1	-9999	-0.31	1	1
YWHAZ	0.011	0	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
YWHAQ	0.011	0	-9999	-10000	0	0
TBC1D4	0.016	0.026	-9999	-0.28	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
SNARE/Synip	0.022	0.011	-9999	-0.23	1	1
YWHAG	0.011	0	-9999	-10000	0	0
ASIP	0.007	0.015	-9999	-0.33	1	1
PRKCI	0.011	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0.008	0	-9999	-10000	0	0
RHOQ	0.011	0	-9999	-10000	0	0
GYS1	0.025	0	-9999	-10000	0	0
PRKCZ	0.01	0.023	-9999	-0.37	2	2
TRIP10	0.011	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.015	0	-9999	-10000	0	0
AS160/14-3-3	-0.006	0.028	-9999	-10000	0	0
VAMP2	0.011	0	-9999	-10000	0	0
SLC2A4	-0.081	0.11	-9999	-0.34	1	1
STX4	0.011	0	-9999	-10000	0	0
GSK3B	0.021	0	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	401	401
LNPEP	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.011	0	-10000	0	-10000	0	0
mol:PIP3	-0.024	0.081	0.23	5	-0.25	57	62
FRAP1	0.008	0.019	-10000	0	-10000	0	0
AKT1	0	0.073	0.2	5	-0.2	57	62
INSR	0.011	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.008	0.002	-10000	0	-10000	0	0
mol:GTP	-0.016	0.049	-10000	0	-0.31	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.005	0.014	-10000	0	-10000	0	0
TSC2	0.011	0	-10000	0	-10000	0	0
RHEB/GDP	-0.014	0.041	-10000	0	-0.27	2	2
TSC1	0.01	0.018	-10000	0	-0.41	1	1
Insulin Receptor/IRS1	-0.017	0.093	-10000	0	-0.3	54	54
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.006	0.017	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.011	0	-10000	0	-10000	0	0
RPS6KB1	0.011	0.041	0.16	5	-0.21	2	7
MAP3K5	0.007	0.025	-10000	0	-0.32	3	3
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
apoptosis	0.007	0.025	-10000	0	-0.32	3	3
mol:LY294002	0	0	-10000	0	-0.001	54	54
EIF4B	0.016	0.038	0.16	5	-0.19	2	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.018	0.033	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.001	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.01	0.09	-10000	0	-0.27	58	58
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.029	0.15	5	-0.14	3	8
FKBP1A	0.011	0	-10000	0	-10000	0	0
RHEB/GTP	-0.014	0.041	-10000	0	-0.27	2	2
mol:Amino Acids	0	0	-10000	0	-0.001	54	54
FKBP12/Rapamycin	0.008	0.001	-10000	0	-10000	0	0
PDPK1	-0.022	0.073	0.21	5	-0.22	57	62
EIF4E	0.011	0	-10000	0	-10000	0	0
ASK1/PP5C	0.012	0.046	-10000	0	-0.58	3	3
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0.002	-10000	0	-10000	0	0
TSC1/TSC2	0.011	0.061	-10000	0	-0.33	2	2
tumor necrosis factor receptor activity	0	0	0.001	54	-10000	0	54
RPS6	0.011	0	-10000	0	-10000	0	0
PPP5C	0.011	0	-10000	0	-10000	0	0
EIF4G1	0.011	0	-10000	0	-10000	0	0
IRS1	-0.026	0.099	-10000	0	-0.32	54	54
INS	0.001	0.003	-10000	0	-10000	0	0
PTEN	0.006	0.044	-10000	0	-0.41	6	6
PDK2	-0.022	0.073	0.21	5	-0.22	57	62
EIF4EBP1	0.012	0.007	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
PPP2R5D	0.013	0.018	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0.001	-10000	0	-10000	0	0
RHEB	0.011	0	-10000	0	-10000	0	0
EIF4A1	0.011	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	6	-0.002	2	8
EEF2	0.014	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.017	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.011	0	-10000	0	-10000	0	0
HDAC4	0.011	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.012	0.032	0.23	9	-10000	0	9
CDKN1A	-0.001	0.027	-10000	0	-0.61	1	1
KAT2B	0.004	0.054	-10000	0	-0.41	9	9
BAX	0.011	0	-10000	0	-10000	0	0
FOXO3	0	0.006	-10000	0	-10000	0	0
FOXO1	0.009	0.031	-10000	0	-0.41	3	3
FOXO4	0.016	0.022	-10000	0	-0.24	4	4
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
TAT	0.007	0.015	-10000	0	-0.33	1	1
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.015	0.078	-10000	0	-0.23	61	61
PPARGC1A	-0.079	0.17	-10000	0	-0.41	116	116
FHL2	0.007	0.04	-10000	0	-0.41	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	-0.001	0.018	-10000	0	-0.28	2	2
HIST2H4A	0.012	0.032	-10000	0	-0.23	9	9
SIRT1/FOXO3a	-0.001	0.015	0.13	1	-0.23	2	3
SIRT1	0.006	0.026	0.18	1	-0.41	2	3
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.015	-10000	0	-0.23	2	2
SIRT1/Histone H1b	0.012	0.026	-10000	0	-0.22	4	4
apoptosis	0.001	0.015	0.23	2	-10000	0	2
SIRT1/PGC1A	-0.051	0.098	0.12	1	-0.24	117	118
p53/SIRT1	-0.001	0.026	0.36	1	-0.28	3	4
SIRT1/FOXO4	0.016	0.024	0.14	1	-0.2	6	7
FOXO1/FHL2/SIRT1	0.015	0.03	-10000	0	-0.21	10	10
HIST1H1E	0.012	0.025	-10000	0	-0.24	2	2
SIRT1/p300	-0.001	0.018	0.14	1	-0.28	2	3
muscle cell differentiation	0.014	0.065	0.19	62	-0.14	1	63
TP53	0.006	0.019	0.18	1	-0.41	1	2
KU70/SIRT1/BAX	-0.001	0.015	-10000	0	-0.23	2	2
CREBBP	0.009	0.025	-10000	0	-0.41	2	2
MEF2D	0.011	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.001	0.02	0.14	1	-0.26	3	4
ACSS2	0.015	0.019	-10000	0	-0.28	2	2
SIRT1/PCAF/MYOD	-0.014	0.065	0.14	1	-0.19	62	63

×

Syndecan-3-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.011	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.015	0.082	-9999	-10000	0	0
Syndecan-3/Neurocan	0.006	0.028	-9999	-10000	0	0
POMC	-0.012	0.088	-9999	-0.35	34	34
EGFR	0	0.066	-9999	-0.4	14	14
Syndecan-3/EGFR	0.015	0.032	-9999	-10000	0	0
AGRP	0.005	0.021	-9999	-0.33	2	2
NCSTN	0.011	0	-9999	-10000	0	0
PSENEN	0.011	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.006	0.047	-9999	-0.41	7	7
APH1A	0.011	0	-9999	-10000	0	0
NCAN	-0.004	0.058	-9999	-0.33	17	17
long-term memory	0.026	0.006	-9999	-10000	0	0
Syndecan-3/IL8	-0.025	0.071	-9999	-0.19	1	1
PSEN1	0.011	0	-9999	-10000	0	0
Src/Cortactin	0.016	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
limb bud formation	-0.001	0.005	-9999	-10000	0	0
MC4R	-0.004	0.057	-9999	-0.33	16	16
SRC	0.011	0	-9999	-10000	0	0
PTN	-0.09	0.18	-9999	-0.41	130	130
FGFR/FGF/Syndecan-3	-0.001	0.005	-9999	-10000	0	0
neuron projection morphogenesis	-0.026	0.078	-9999	-0.29	3	3
Syndecan-3/AgRP	0.011	0.015	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.004	0.028	-9999	-10000	0	0
Fyn/Cortactin	0.016	0	-9999	-10000	0	0
SDC3	-0.001	0.005	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.025	0.07	-9999	-0.19	1	1
IL8	-0.088	0.15	-9999	-0.33	158	158
Syndecan-3/Fyn/Cortactin	0.026	0.006	-9999	-10000	0	0
Syndecan-3/CASK	0	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.01	0.073	-9999	-0.24	48	48
Gamma Secretase	0.03	0.024	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.002	-9999	-10000	0	0
RAS family/GTP	0.009	0.05	-9999	-0.27	5	5
NFATC4	0.015	0.047	-9999	-0.33	2	2
ERBB2IP	0.011	0.001	-9999	-10000	0	0
HSP90 (dimer)	0.011	0	-9999	-10000	0	0
mammary gland morphogenesis	0.003	0.048	-9999	-0.21	13	13
JUN	-0.006	0.068	-9999	-0.34	4	4
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	0.014	0.048	-9999	-0.32	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.003	0.052	-9999	-0.21	22	22
AKT1	0.009	0.001	-9999	-10000	0	0
BAD	0.015	0.001	-9999	-10000	0	0
MAPK10	-0.009	0.067	-9999	-0.22	12	12
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.004	0.052	-9999	-0.22	13	13
RAF1	0.011	0.055	-9999	-0.28	5	5
ErbB2/ErbB3/neuregulin 2	-0.028	0.086	-9999	-0.22	85	85
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	0.001	0.062	-9999	-0.2	17	17
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	-0.078	0.18	-9999	-0.41	65	65
FOS	-0.12	0.24	-9999	-0.47	168	168
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	0.003	0.048	-9999	-0.21	13	13
MAPK3	-0.043	0.13	-9999	-0.48	10	10
MAPK1	-0.043	0.13	-9999	-0.48	10	10
JAK2	0.011	0.052	-9999	-0.32	2	2
NF2	0	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.01	0.052	-9999	-0.23	22	22
NRG1	-0.006	0.081	-9999	-0.41	21	21
GRB2/SOS1	0.016	0.001	-9999	-10000	0	0
MAPK8	0.004	0.058	-9999	-0.22	28	28
MAPK9	0.021	0.029	-9999	-0.16	2	2
ERBB2	-0.006	0.036	-9999	-0.23	14	14
ERBB3	0.008	0.031	-9999	-0.42	3	3
SHC1	0.01	0.001	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
apoptosis	0.001	0.006	-9999	-10000	0	0
STAT3 (dimer)	0.017	0.003	-9999	-10000	0	0
RNF41	0.02	0.003	-9999	-10000	0	0
FRAP1	0.008	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.007	0.029	-9999	-0.23	2	2
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.029	-9999	-0.18	14	14
CHRNA1	-0.053	0.12	-9999	-0.3	58	58
myelination	0.02	0.044	-9999	-0.31	2	2
PPP3CB	0.005	0.045	-9999	-0.3	2	2
KRAS	0.01	0.015	-9999	-0.33	1	1
RAC1-CDC42/GDP	0.022	0.046	-9999	-0.34	2	2
NRG2	-0.052	0.15	-9999	-0.41	81	81
mol:GDP	0.01	0.052	-9999	-0.23	22	22
SOS1	0.011	0.001	-9999	-10000	0	0
MAP2K2	0.011	0.061	-9999	-0.3	5	5
SRC	0.011	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0.014	0.048	-9999	-0.31	2	2
MAP2K1	-0.048	0.13	-9999	-0.43	15	15
heart morphogenesis	0.003	0.048	-9999	-0.21	13	13
RAS family/GDP	0.016	0.048	-9999	-0.28	4	4
GRB2	0.011	0.001	-9999	-10000	0	0
PRKACA	-0.001	0.003	-9999	-10000	0	0
CHRNE	0.006	0.022	-9999	-0.18	4	4
HSP90AA1	0.011	0	-9999	-10000	0	0
activation of caspase activity	-0.009	0.001	-9999	-10000	0	0
nervous system development	0.003	0.048	-9999	-0.21	13	13
CDC42	0.011	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.007	0.048	-10000	0	-1.1	1	1
oxygen homeostasis	-0.002	0.014	-10000	0	-10000	0	0
TCEB2	0.01	0.015	-10000	0	-0.33	1	1
TCEB1	0.011	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.017	0.04	-10000	0	-0.29	4	4
EPO	-0.023	0.21	-10000	0	-0.55	22	22
FIH (dimer)	0.009	0.013	-10000	0	-10000	0	0
APEX1	0.007	0.015	-10000	0	-10000	0	0
SERPINE1	-0.015	0.2	-10000	0	-0.54	16	16
FLT1	-0.012	0.061	-10000	0	-1.1	1	1
ADORA2A	-0.013	0.19	-10000	0	-0.49	15	15
germ cell development	-0.022	0.21	-10000	0	-0.52	27	27
SLC11A2	-0.013	0.19	-10000	0	-0.5	15	15
BHLHE40	-0.013	0.19	-10000	0	-0.5	15	15
HIF1AN	0.009	0.013	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.005	0.12	-10000	0	-0.35	7	7
ETS1	0.021	0.02	-10000	0	-0.42	1	1
CITED2	-0.036	0.18	-10000	0	-1	17	17
KDR	-0.066	0.26	-10000	0	-1.1	33	33
PGK1	-0.013	0.19	-10000	0	-0.5	15	15
SIRT1	0.009	0.025	-10000	0	-0.41	2	2
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	-0.017	0.22	-10000	0	-0.55	18	18
EPAS1	0.01	0.088	-10000	0	-0.37	3	3
SP1	0.017	0.001	-10000	0	-10000	0	0
ABCG2	-0.14	0.3	-10000	0	-0.54	102	102
EFNA1	-0.013	0.19	-10000	0	-0.51	15	15
FXN	-0.013	0.19	-10000	0	-0.49	15	15
POU5F1	-0.024	0.21	-10000	0	-0.54	27	27
neuron apoptosis	0.017	0.21	0.54	18	-10000	0	18
EP300	0.011	0	-10000	0	-10000	0	0
EGLN3	0.006	0.033	-10000	0	-0.35	4	4
EGLN2	0.009	0.013	-10000	0	-10000	0	0
EGLN1	0.009	0.013	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.022	0.014	-10000	0	-0.2	2	2
VHL	0.01	0.018	-10000	0	-0.41	1	1
ARNT	0.007	0.015	-10000	0	-10000	0	0
SLC2A1	-0.013	0.19	-10000	0	-0.5	14	14
TWIST1	-0.039	0.23	-10000	0	-0.54	57	57
ELK1	0.016	0.01	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0	0.11	-10000	0	-0.43	3	3
VEGFA	-0.013	0.19	-10000	0	-0.51	14	14
CREBBP	0.009	0.025	-10000	0	-0.41	2	2

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.039	0.042	-9999	-0.54	1	1
UGCG	0.004	0.094	-9999	-0.63	11	11
AKT1/mTOR/p70S6K/Hsp90/TERT	0.023	0.098	-9999	-0.29	18	18
mol:GTP	0	0	-9999	-10000	0	0
mol:glucosylceramide	0.006	0.093	-9999	-0.62	11	11
mol:DAG	0	0.001	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.039	0.11	-9999	-0.34	60	60
FRAP1	0.019	0.15	-9999	-0.39	60	60
FOXO3	0.039	0.098	-9999	-0.36	17	17
AKT1	0.034	0.1	-9999	-0.38	17	17
GAB2	0.007	0.036	-9999	-0.41	4	4
SMPD1	0.017	0.02	-9999	-10000	0	0
SGMS1	0.017	0.02	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
mol:GDP	0.013	0.027	-9999	-0.24	6	6
CALM1	0.011	0	-9999	-10000	0	0
cell proliferation	0.021	0.074	-9999	-0.29	21	21
EIF3A	0.011	0	-9999	-10000	0	0
PI3K	0.016	0.032	-9999	-0.28	6	6
RPS6KB1	0.014	0.023	-9999	-10000	0	0
mol:sphingomyelin	0	0.001	-9999	-10000	0	0
natural killer cell activation	0	0.003	-9999	-0.012	10	10
JAK3	0.01	0.029	-9999	-0.33	4	4
PIK3R1	0.008	0.041	-9999	-0.41	5	5
JAK1	0.011	0.026	-9999	-0.41	2	2
NFKB1	0.01	0.018	-9999	-0.41	1	1
MYC	0.03	0.15	-9999	-0.91	10	10
MYB	0.012	0.047	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.039	0.071	-9999	-0.3	8	8
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.025	0.021	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.039	0.07	-9999	-0.29	8	8
Rac1/GDP	0.019	0.025	-9999	-0.21	6	6
T cell proliferation	0.043	0.068	-9999	-0.35	3	3
SHC1	0.011	0.004	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.002	0.007	-9999	-10000	0	0
PRKCZ	0.043	0.069	-9999	-0.36	3	3
NF kappa B1 p50/RelA	-0.032	0.11	-9999	-0.34	60	60
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.034	0.045	-9999	-0.44	2	2
HSP90AA1	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
IL2RA	-0.003	0.066	-9999	-0.33	21	21
IL2RB	0.012	0.018	-9999	-0.41	1	1
TERT	-0.11	0.16	-9999	-0.33	198	198
E2F1	0.014	0.032	-9999	-10000	0	0
SOS1	0.011	0.004	-9999	-10000	0	0
RPS6	0.011	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.003	-9999	-10000	0	0
PTPN11	0.011	0.004	-9999	-10000	0	0
IL2RG	0.006	0.047	-9999	-0.35	9	9
actin cytoskeleton organization	0.043	0.068	-9999	-0.35	3	3
GRB2	0.011	0.004	-9999	-10000	0	0
IL2	-0.005	0.06	-9999	-0.33	18	18
PIK3CA	0.011	0.018	-9999	-0.41	1	1
Rac1/GTP	0.024	0.025	-9999	-0.19	6	6
LCK	0.009	0.034	-9999	-0.34	5	5
BCL2	-0.018	0.26	-9999	-0.82	50	50

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.003	0.052	0.36	11	-10000	0	11
PI3K Class IB/PDE3B	0.003	0.052	-10000	0	-0.36	11	11
PDE3B	0.003	0.052	-10000	0	-0.36	11	11

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.017	0.05	-9999	-0.21	18	18
MAP4K1	0.003	0.052	-9999	-0.33	13	13
MAP3K8	0.009	0.031	-9999	-0.41	3	3
PRKCB	-0.014	0.099	-9999	-0.41	32	32
DBNL	0.011	0	-9999	-10000	0	0
CRKL	0.011	0	-9999	-10000	0	0
MAP3K1	0.029	0.038	-9999	-0.22	1	1
JUN	-0.01	0.14	-9999	-0.52	38	38
MAP3K7	0.029	0.038	-9999	-0.22	1	1
GRAP2	-0.002	0.073	-9999	-0.41	17	17
CRK	0.011	0	-9999	-10000	0	0
MAP2K4	0.034	0.039	-9999	-10000	0	0
LAT	0.011	0	-9999	-10000	0	0
LCP2	0.01	0.015	-9999	-0.33	1	1
MAPK8	-0.014	0.15	-9999	-0.55	38	38
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.024	0.04	-9999	-0.24	1	1
LAT/GRAP2/SLP76/HPK1/HIP-55	0.022	0.047	-9999	-0.31	2	2

×

EPO signaling 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
BCL2L1	0.021	0.11	-10000	0	-0.44	6	6
CRKL	0.019	0.053	-10000	0	-0.24	6	6
mol:DAG	0.019	0.066	-10000	0	-0.24	19	19
HRAS	0.035	0.05	-10000	0	-10000	0	0
MAPK8	0.015	0.048	-10000	0	-0.19	22	22
RAP1A	0.019	0.053	-10000	0	-0.24	6	6
GAB1	0.017	0.057	-10000	0	-0.24	8	8
MAPK14	0.018	0.041	-10000	0	-0.21	3	3
EPO	-0.003	0.073	-10000	0	-0.4	17	17
PLCG1	0.019	0.067	-10000	0	-0.24	19	19
EPOR/TRPC2/IP3 Receptors	0.007	0.038	-10000	0	-0.32	7	7
RAPGEF1	0.011	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.012	0.049	-10000	0	-0.22	18	18
GAB1/SHC/GRB2/SOS1	-0.012	0.036	-10000	0	-0.22	2	2
EPO/EPOR (dimer)	0.005	0.057	-10000	0	-0.26	24	24
IRS2	-0.007	0.085	-10000	0	-0.26	19	19
STAT1	0.019	0.088	-10000	0	-0.37	6	6
STAT5B	0.018	0.079	-10000	0	-0.34	6	6
cell proliferation	0.021	0.044	-10000	0	-0.19	7	7
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.013	0.04	-10000	0	-0.23	7	7
TEC	0.019	0.054	-10000	0	-0.24	6	6
SOCS3	0.009	0.025	-10000	0	-0.41	2	2
STAT1 (dimer)	0.019	0.087	-10000	0	-0.37	6	6
JAK2	0.004	0.054	-10000	0	-0.41	9	9
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
EPO/EPOR (dimer)/JAK2	0.024	0.06	-10000	0	-0.23	8	8
EPO/EPOR	0.005	0.057	-10000	0	-0.26	24	24
LYN	0.011	0.004	-10000	0	-10000	0	0
TEC/VAV2	0.025	0.053	-10000	0	-0.22	6	6
elevation of cytosolic calcium ion concentration	0.007	0.038	-10000	0	-0.32	7	7
SHC1	0.011	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.017	0.048	-10000	0	-0.22	16	16
mol:IP3	0.019	0.066	-10000	0	-0.24	19	19
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.003	0.085	-10000	0	-0.25	22	22
SH2B3	0.01	0.019	-10000	0	-0.41	1	1
NFKB1	0.018	0.042	-10000	0	-0.21	4	4
EPO/EPOR (dimer)/JAK2/SOCS3	-0.01	0.049	0.23	1	-0.22	27	28
PTPN6	0.013	0.056	-10000	0	-0.23	8	8
TEC/VAV2/GRB2	0.03	0.051	-10000	0	-0.21	6	6
EPOR	0.007	0.038	-10000	0	-0.32	7	7
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	-0.012	0.036	-10000	0	-0.21	5	5
SOS1	0.011	0	-10000	0	-10000	0	0
PLCG2	0.01	0.023	-10000	0	-0.37	2	2
CRKL/CBL/C3G	0.03	0.051	-10000	0	-0.21	6	6
VAV2	0.019	0.053	-10000	0	-0.24	6	6
CBL	0.019	0.053	-10000	0	-0.24	6	6
SHC/Grb2/SOS1	-0.012	0.036	-10000	0	-0.21	6	6
STAT5A	0.018	0.079	-10000	0	-0.34	6	6
GRB2	0.011	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.024	0.1	-10000	0	-0.27	51	51
LYN/PLCgamma2	0.015	0.017	-10000	0	-0.25	2	2
PTPN11	0.011	0	-10000	0	-10000	0	0
BTK	0.018	0.056	-10000	0	-0.27	6	6
BCL2	-0.024	0.25	-10000	0	-0.79	50	50

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.018	-10000	0	-0.28	2	2
MAP4K4	0.028	0.034	-10000	0	-0.4	1	1
BAG4	0.009	0.031	-10000	0	-0.41	3	3
PKC zeta/ceramide	-0.002	0.016	0.12	2	-0.18	2	4
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	0.004	0.055	-10000	0	-0.39	10	10
BAX	0.002	0.006	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AKT1	0.014	0.002	-10000	0	-10000	0	0
BAD	-0.002	0.012	0.13	2	-10000	0	2
SMPD1	0.015	0.025	-10000	0	-0.17	2	2
RB1	-0.003	0.02	0.13	2	-0.22	3	5
FADD/Caspase 8	0.037	0.032	-10000	0	-0.39	1	1
MAP2K4	0.003	0.014	0.14	1	-0.19	1	2
NSMAF	0.011	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.003	0.016	0.13	2	-0.19	2	4
EGF	-0.006	0.073	-10000	0	-0.34	25	25
mol:ceramide	-0.009	0.013	0.13	2	-10000	0	2
MADD	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.017	0.018	-10000	0	-0.28	2	2
ASAH1	0.011	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.004	0.02	0.13	2	-0.22	3	5
cell proliferation	-0.011	0.069	-10000	0	-0.15	97	97
BID	0.024	0.025	-10000	0	-0.29	1	1
MAP3K1	-0.002	0.012	0.13	2	-10000	0	2
EIF2A	0.009	0.011	0.14	1	-10000	0	1
TRADD	0.011	0	-10000	0	-10000	0	0
CRADD	0.011	0	-10000	0	-10000	0	0
MAPK3	0.011	0.016	0.13	2	-0.17	2	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.011	0.016	0.13	2	-0.17	2	4
Cathepsin D/ceramide	-0.001	0.014	0.12	2	-0.16	1	3
FADD	0.028	0.034	-10000	0	-0.4	1	1
KSR1	-0.003	0.017	0.13	2	-0.21	2	4
MAPK8	0.005	0.028	0.14	1	-0.22	7	8
PRKRA	-0.002	0.012	0.13	2	-10000	0	2
PDGFA	0.009	0.025	-10000	0	-0.41	2	2
TRAF2	0.011	0	-10000	0	-10000	0	0
IGF1	-0.067	0.16	-10000	0	-0.41	101	101
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.009	0.013	0.13	2	-10000	0	2
CTSD	0.01	0.015	-10000	0	-0.33	1	1
regulation of nitric oxide biosynthetic process	0.016	0.013	-10000	0	-0.28	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.011	0.073	-10000	0	-0.17	31	31
PRKCD	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.023	-10000	0	-0.37	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.017	0.018	-10000	0	-0.28	2	2
RelA/NF kappa B1	0.016	0.013	-10000	0	-0.28	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.011	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.024	0.036	-10000	0	-0.43	1	1
TNFR1A/BAG4/TNF-alpha	-0.003	0.067	-10000	0	-0.18	71	71
mol:Sphingosine-1-phosphate	0.017	0.018	-10000	0	-0.28	2	2
MAP2K1	0.008	0.016	0.14	1	-0.18	2	3
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
CYCS	0.013	0.04	0.14	51	-10000	0	51
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
TNFR1A/BAG4	0.015	0.022	-10000	0	-0.28	3	3
EIF2AK2	0.003	0.011	0.13	2	-10000	0	2
TNF-alpha/TNFR1A/FAN	-0.002	0.065	-10000	0	-0.17	68	68
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.03	0.023	-10000	0	-0.22	1	1
MAP2K2	0.008	0.016	0.14	1	-0.18	2	3
SMPD3	0.016	0.032	-10000	0	-0.25	4	4
TNF	-0.032	0.11	-10000	0	-0.33	68	68
PKC zeta/PAR4	0.015	0.016	-10000	0	-0.25	2	2
mol:PHOSPHOCHOLINE	-0.004	0.023	0.16	4	-10000	0	4
NF kappa B1/RelA/I kappa B alpha	0.032	0.015	-10000	0	-10000	0	0
AIFM1	0.013	0.04	0.14	51	-10000	0	51
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

Caspase cascade in apoptosis

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
TOP1	0.013	0.048	-10000	0	-0.29	6	6
ACTA1	0.004	0.058	0.16	3	-0.3	10	13
NUMA1	0.013	0.048	-10000	0	-0.25	10	10
SPTAN1	0.007	0.058	0.16	5	-0.3	10	15
LIMK1	0.007	0.058	0.16	5	-0.3	10	15
BIRC3	0.004	0.055	-10000	0	-0.39	10	10
BIRC2	0.011	0	-10000	0	-10000	0	0
BAX	0.011	0	-10000	0	-10000	0	0
CASP10	-0.002	0.075	-10000	0	-0.2	60	60
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.011	0	-10000	0	-10000	0	0
PTK2	0.013	0.048	-10000	0	-0.25	10	10
DIABLO	0.011	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.007	0.057	0.16	5	-0.3	10	15
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.011	0	-10000	0	-10000	0	0
GSN	0.004	0.06	0.16	4	-0.26	15	19
MADD	0.011	0	-10000	0	-10000	0	0
TFAP2A	0.028	0.039	-10000	0	-0.58	2	2
BID	0.008	0.037	-10000	0	-0.18	11	11
MAP3K1	0.008	0.023	-10000	0	-0.17	2	2
TRADD	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.007	0.058	0.16	5	-0.3	10	15
CASP9	0.011	0	-10000	0	-10000	0	0
DNA repair	-0.005	0.022	0.14	1	-0.16	5	6
neuron apoptosis	0.019	0.008	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.013	0.055	0.16	5	-0.28	10	15
APAF1	0.011	0	-10000	0	-10000	0	0
CASP6	0.022	0.032	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
ICAD/CAD	0.012	0.056	0.16	5	-0.29	10	15
CASP7	-0.005	0.032	0.25	8	-10000	0	8
KRT18	0.013	0.032	-10000	0	-0.7	1	1
apoptosis	0.014	0.053	0.18	5	-0.24	10	15
DFFA	0.007	0.058	0.16	5	-0.3	10	15
DFFB	0.007	0.058	0.16	5	-0.3	10	15
PARP1	0.005	0.022	0.16	5	-0.14	1	6
actin filament polymerization	-0.009	0.058	0.28	11	-0.16	3	14
TNF	-0.032	0.11	-10000	0	-0.33	68	68
CYCS	0.009	0.031	-10000	0	-0.15	8	8
SATB1	-0.005	0.081	-10000	0	-0.37	5	5
SLK	0.007	0.058	0.16	5	-0.3	10	15
p15 BID/BAX	0.013	0.033	-10000	0	-0.26	2	2
CASP2	0.03	0.03	-10000	0	-0.3	1	1
JNK cascade	-0.008	0.023	0.17	2	-10000	0	2
CASP3	0.001	0.061	0.17	5	-0.32	10	15
LMNB2	0.032	0.024	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
CASP4	0.01	0.018	-10000	0	-0.41	1	1
Mammalian IAPs/DIABLO	0.024	0.029	-10000	0	-0.2	8	8
negative regulation of DNA binding	0.028	0.038	-10000	0	-0.58	2	2
stress fiber formation	0.007	0.057	0.16	5	-0.3	10	15
GZMB	-0.011	0.086	-10000	0	-0.25	59	59
CASP1	0.012	0.021	-10000	0	-0.28	3	3
LMNB1	0.032	0.024	-10000	0	-10000	0	0
APP	0.02	0.008	-10000	0	-10000	0	0
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	0.01	0.053	0.18	5	-0.24	10	15
LMNA	0.032	0.024	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.026	0.032	-10000	0	-0.32	1	1
LRDD	0.011	0	-10000	0	-10000	0	0
SREBF1	0.007	0.058	0.16	5	-0.3	10	15
APAF-1/Caspase 9	-0.001	0.017	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.013	0.048	-10000	0	-0.24	10	10
CFL2	0.009	0.059	0.16	3	-0.28	11	14
GAS2	-0.008	0.081	0.17	4	-0.23	44	48
positive regulation of apoptosis	0.035	0.024	-10000	0	-10000	0	0
PRF1	0.005	0.049	-10000	0	-0.37	9	9

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.011	0.018	-10000	0	-0.4	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.011	0.097	0.46	5	-10000	0	5
IL27/IL27R/JAK1	-0.017	0.11	-10000	0	-0.84	3	3
TBX21	0.001	0.12	-10000	0	-0.56	6	6
IL12B	0.006	0.015	-10000	0	-0.33	1	1
IL12A	0.002	0.041	-10000	0	-0.24	15	15
IL6ST	-0.056	0.16	-10000	0	-0.42	86	86
IL27RA/JAK1	0.012	0.071	-10000	0	-1.1	2	2
IL27	0.002	0.05	-10000	0	-0.33	12	12
TYK2	0.012	0.005	-10000	0	-10000	0	0
T-helper cell lineage commitment	0	0.047	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.011	0.097	0.46	5	-10000	0	5
T cell proliferation during immune response	0.011	0.097	0.46	5	-10000	0	5
MAPKKK cascade	-0.011	0.097	-10000	0	-0.46	5	5
STAT3	0.011	0	-10000	0	-10000	0	0
STAT2	0.011	0	-10000	0	-10000	0	0
STAT1	0.01	0.021	-10000	0	-0.33	2	2
IL12RB1	-0.001	0.065	-10000	0	-0.35	18	18
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.003	0.12	-10000	0	-0.47	11	11
IL27/IL27R/JAK2/TYK2	-0.012	0.098	-10000	0	-0.47	5	5
positive regulation of T cell mediated cytotoxicity	-0.011	0.097	-10000	0	-0.46	5	5
STAT1 (dimer)	-0.041	0.12	0.47	4	-0.78	4	8
JAK2	0.004	0.054	-10000	0	-0.41	9	9
JAK1	0.01	0.025	-10000	0	-0.41	2	2
STAT2 (dimer)	-0.005	0.093	-10000	0	-0.44	5	5
T cell proliferation	-0.012	0.1	-10000	0	-0.41	12	12
IL12/IL12R/TYK2/JAK2	0.014	0.052	-10000	0	-0.52	1	1
IL17A	-0.002	0.046	-10000	0	-10000	0	0
mast cell activation	0.011	0.097	0.46	5	-10000	0	5
IFNG	0	0.022	-10000	0	-0.075	4	4
T cell differentiation	-0.002	0.004	-10000	0	-0.017	8	8
STAT3 (dimer)	-0.005	0.093	-10000	0	-0.44	5	5
STAT5A (dimer)	-0.005	0.093	-10000	0	-0.44	5	5
STAT4 (dimer)	-0.005	0.093	-10000	0	-0.44	5	5
STAT4	0.01	0.018	-10000	0	-0.41	1	1
T cell activation	-0.007	0.009	0.12	2	-10000	0	2
IL27R/JAK2/TYK2	-0.015	0.11	-10000	0	-1	2	2
GATA3	-0.012	0.13	-10000	0	-1.2	6	6
IL18	0.005	0.03	-10000	0	-0.23	9	9
positive regulation of mast cell cytokine production	-0.005	0.092	-10000	0	-0.43	5	5
IL27/EBI3	0.005	0.055	-10000	0	-0.25	22	22
IL27RA	0.004	0.075	-10000	0	-1.2	2	2
IL6	-0.006	0.083	-10000	0	-0.38	25	25
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.002	0.036	0.46	2	-10000	0	2
IL1B	0.007	0.025	-10000	0	-0.29	4	4
EBI3	0.003	0.053	-10000	0	-0.34	13	13
TNF	-0.02	0.078	-10000	0	-0.23	68	68

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.024	0.03	-9999	-0.2	9	9
HDAC3	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.013	0.004	-9999	-10000	0	0
GATA1/HDAC5	0.013	0.004	-9999	-10000	0	0
GATA2/HDAC5	-0.013	0.088	-9999	-0.28	53	53
HDAC5/BCL6/BCoR	0.022	0.011	-9999	-0.23	1	1
HDAC9	0.003	0.057	-9999	-0.41	10	10
Glucocorticoid receptor/Hsp90/HDAC6	-0.014	0.088	-9999	-0.23	79	79
HDAC4/ANKRA2	0.016	0.013	-9999	-0.28	1	1
HDAC5/YWHAB	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	-0.03	0.12	-9999	-0.41	53	53
HDAC4/RFXANK	0.015	0.017	-9999	-0.22	3	3
BCOR	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.011	0	-9999	-10000	0	0
HDAC5	0.011	0	-9999	-10000	0	0
GNB1/GNG2	0.011	0.039	-9999	-0.27	10	10
Histones	0.029	0.026	-9999	-10000	0	0
ADRBK1	0.011	0	-9999	-10000	0	0
HDAC4	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.016	0.013	-9999	-0.28	1	1
HDAC4/Ubc9	0.016	0	-9999	-10000	0	0
HDAC7	0.011	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.016	0	-9999	-10000	0	0
TUBA1B	0.011	0	-9999	-10000	0	0
HDAC6	0.011	0	-9999	-10000	0	0
HDAC5/RFXANK	0.015	0.017	-9999	-0.22	3	3
CAMK4	0.004	0.05	-9999	-0.36	10	10
Tubulin/HDAC6	0.02	0.024	-9999	-0.19	7	7
SUMO1	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
GATA1	0.006	0.005	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
NR3C1	-0.05	0.15	-9999	-0.41	79	79
SUMO1/HDAC4	0.025	0	-9999	-10000	0	0
SRF	0.011	0	-9999	-10000	0	0
HDAC4/YWHAB	0.016	0	-9999	-10000	0	0
Tubulin	0.013	0.028	-9999	-0.24	7	7
HDAC4/14-3-3 E	0.016	0	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
RANGAP1	0.011	0	-9999	-10000	0	0
BCL6/BCoR	0.016	0.013	-9999	-0.28	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.022	0	-9999	-10000	0	0
HDAC4/SRF	0.018	0.029	-9999	-0.23	4	4
HDAC4/ER alpha	-0.017	0.094	-9999	-0.28	62	62
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.029	0.026	-9999	-10000	0	0
cell motility	0.019	0.024	-9999	-0.19	7	7
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
HDAC7/HDAC3	0.016	0	-9999	-10000	0	0
BCL6	0.01	0.018	-9999	-0.41	1	1
HDAC4/CaMK II delta B	0.011	0	-9999	-10000	0	0
Hsp90/HDAC6	0.016	0	-9999	-10000	0	0
ESR1	-0.037	0.13	-9999	-0.41	62	62
HDAC6/HDAC11	0.016	0.01	-9999	-0.22	1	1
Ran/GTP/Exportin 1	0.027	0	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
MEF2C	-0.03	0.12	-9999	-0.41	53	53
RAN	0.011	0	-9999	-10000	0	0
HDAC4/MEF2C	0.012	0.063	-9999	-10000	0	0
GNG2	0.003	0.056	-9999	-0.4	10	10
NCOR2	0.011	0	-9999	-10000	0	0
TUBB2A	0.006	0.041	-9999	-0.35	7	7
HDAC11	0.01	0.015	-9999	-0.33	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
RANBP2	0.011	0	-9999	-10000	0	0
ANKRA2	0.01	0.018	-9999	-0.41	1	1
RFXANK	0.009	0.025	-9999	-0.33	3	3
nuclear import	-0.024	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.02	-9999	-0.28	2	2
CRKL	0.011	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
DOCK1	0.006	0.047	-9999	-0.41	7	7
ITGA4	0.009	0.029	-9999	-0.38	3	3
alpha4/beta7 Integrin/MAdCAM1	0.013	0.049	-9999	-0.2	2	2
EPO	-0.004	0.072	-9999	-0.41	17	17
alpha4/beta7 Integrin	0.014	0.023	-9999	-0.25	4	4
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.015	0.021	-9999	-0.26	3	3
EPO/EPOR (dimer)	0.002	0.057	-9999	-0.26	24	24
lamellipodium assembly	0.025	0.028	-9999	-0.25	4	4
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PI3K	0.013	0.031	-9999	-0.28	6	6
ARF6	0.011	0	-9999	-10000	0	0
JAK2	0.013	0.056	-9999	-0.22	27	27
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
MADCAM1	-0.016	0.089	-9999	-0.33	41	41
cell adhesion	0.012	0.049	-9999	-0.2	2	2
CRKL/CBL	0.016	0	-9999	-10000	0	0
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.009	0.063	-9999	-0.21	40	40
ITGB7	0.01	0.015	-9999	-0.33	1	1
RAC1	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.003	0.07	-9999	-0.24	41	41
p130Cas/Crk/Dock1	0.024	0.06	-9999	-0.43	2	2
VCAM1	-0.02	0.11	-9999	-0.41	40	40
RHOA	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.027	0.016	-9999	-0.2	2	2
BCAR1	0.015	0.059	-9999	-0.38	2	2
EPOR	0.007	0.038	-9999	-0.33	7	7
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.002	0.026	-9999	-0.26	4	4

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	0.018	0.23	-9999	-1.2	11	11
IL23A	0.019	0.21	-9999	-1	9	9
NF kappa B1 p50/RelA/I kappa B alpha	-0.042	0.16	-9999	-0.95	10	10
positive regulation of T cell mediated cytotoxicity	0.019	0.22	-9999	-1	10	10
ITGA3	0.023	0.2	-9999	-1	8	8
IL17F	0.032	0.15	-9999	-0.63	10	10
IL12B	0.015	0.025	-9999	-0.32	1	1
STAT1 (dimer)	0.018	0.21	-9999	-1	10	10
CD4	0.025	0.2	-9999	-0.99	8	8
IL23	0.015	0.2	-9999	-1	9	9
IL23R	0.021	0.052	-9999	-10000	0	0
IL1B	0.017	0.22	-9999	-1.1	11	11
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	0.02	0.2	-9999	-1	8	8
TYK2	0.015	0.013	-9999	-10000	0	0
STAT4	0.01	0.018	-9999	-0.41	1	1
STAT3	0.011	0	-9999	-10000	0	0
IL18RAP	0.005	0.044	-9999	-0.38	7	7
IL12RB1	0.003	0.07	-9999	-0.36	18	18
PIK3CA	0.01	0.018	-9999	-0.41	1	1
IL12Rbeta1/TYK2	0.011	0.052	-9999	-0.25	18	18
IL23R/JAK2	0.028	0.075	-9999	-10000	0	0
positive regulation of chronic inflammatory response	0.019	0.22	-9999	-1	10	10
natural killer cell activation	-0.001	0.005	-9999	-10000	0	0
JAK2	0.013	0.059	-9999	-0.42	9	9
PIK3R1	0.007	0.04	-9999	-0.41	5	5
NFKB1	0.011	0.018	-9999	-0.41	1	1
RELA	0.012	0.002	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.016	0.2	-9999	-0.96	9	9
ALOX12B	0.019	0.2	-9999	-0.96	9	9
CXCL1	-0.003	0.24	-9999	-1.1	15	15
T cell proliferation	0.019	0.22	-9999	-1	10	10
NFKBIA	0.012	0.002	-9999	-10000	0	0
IL17A	0.043	0.13	-9999	-0.51	8	8
PI3K	-0.025	0.18	-9999	-0.96	10	10
IFNG	0.003	0.019	-9999	-10000	0	0
STAT3 (dimer)	-0.046	0.16	-9999	-0.92	10	10
IL18R1	0.007	0.036	-9999	-0.41	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.03	0.14	-9999	-0.64	7	7
IL18/IL18R	0.014	0.045	-9999	-0.21	19	19
macrophage activation	-0.003	0.01	-9999	-0.042	10	10
TNF	0.015	0.22	-9999	-1.3	6	6
STAT3/STAT4	-0.024	0.18	-9999	-0.96	10	10
STAT4 (dimer)	0.019	0.21	-9999	-1	9	9
IL18	0.005	0.044	-9999	-0.33	9	9
IL19	0.006	0.2	-9999	-0.97	9	9
STAT5A (dimer)	0.019	0.21	-9999	-1.1	9	9
STAT1	0.01	0.021	-9999	-0.33	2	2
SOCS3	0.009	0.025	-9999	-0.41	2	2
CXCL9	0.004	0.23	-9999	-1.2	10	10
MPO	0.024	0.2	-9999	-0.99	8	8
positive regulation of humoral immune response	0.019	0.22	-9999	-1	10	10
IL23/IL23R/JAK2/TYK2	0.018	0.22	-9999	-1.1	10	10
IL6	0.002	0.27	-9999	-1.1	20	20
STAT5A	0.01	0.018	-9999	-0.41	1	1
IL2	-0.008	0.06	-9999	-0.33	18	18
positive regulation of tyrosine phosphorylation of STAT protein	-0.001	0.005	-9999	-10000	0	0
CD3E	0.014	0.24	-9999	-1.1	14	14
keratinocyte proliferation	0.019	0.22	-9999	-1	10	10
NOS2	0.013	0.23	-9999	-1	15	15

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.01	0.015	-10000	0	-0.2	3	3
TRAF2/ASK1	0.014	0.018	-10000	0	-0.23	3	3
ATM	0.011	0	-10000	0	-10000	0	0
MAP2K3	0.026	0.02	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.028	0.025	-10000	0	-0.22	3	3
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.001	0.069	-10000	0	-0.41	15	15
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.011	0	-10000	0	-10000	0	0
GADD45A	0.011	0	-10000	0	-10000	0	0
GADD45B	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.011	0	-10000	0	-10000	0	0
MAP3K6	0.011	0	-10000	0	-10000	0	0
MAP3K7	0.011	0	-10000	0	-10000	0	0
MAP3K4	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.015	0.022	-10000	0	-0.28	3	3
TAK1/TAB family	0.001	0.009	0.15	2	-10000	0	2
RAC1/OSM/MEKK3	0.021	0	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.001	0.009	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.045	0.13	-10000	0	-0.33	89	89
CCM2	0.011	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.017	0.072	-10000	0	-0.18	89	89
MAPK11	0.009	0.025	-10000	0	-0.41	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.009	0.067	-10000	0	-0.16	92	92
OSM/MEKK3	0.016	0	-10000	0	-10000	0	0
TAOK1	0.013	0.018	-10000	0	-0.28	2	2
TAOK2	0.014	0	-10000	0	-10000	0	0
TAOK3	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.011	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.009	0.031	-10000	0	-0.41	3	3
MAP3K10	0.011	0	-10000	0	-10000	0	0
MAP3K3	0.011	0	-10000	0	-10000	0	0
TRX/ASK1	0.012	0.018	-10000	0	-0.23	3	3
GADD45/MTK1/MTK1	0.02	0.035	-10000	0	-0.19	15	15

×

ceramide signaling pathway

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
MAP4K4	0.032	0.038	-10000	0	-0.38	1	1
BAG4	0.009	0.031	-10000	0	-0.41	3	3
BAD	0.023	0.014	-10000	0	-0.12	1	1
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BAX	0.023	0.014	-10000	0	-0.12	1	1
EnzymeConsortium:3.1.4.12	0.01	0.01	-10000	0	-0.092	1	1
IKBKB	0.037	0.037	-10000	0	-0.36	1	1
MAP2K2	0.031	0.017	-10000	0	-0.16	1	1
MAP2K1	0.031	0.017	-10000	0	-0.16	1	1
SMPD1	0.015	0.01	-10000	0	-0.087	1	1
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.038	0.037	-10000	0	-0.37	1	1
MAP2K4	0.027	0.016	-10000	0	-0.16	1	1
protein ubiquitination	0.038	0.037	-10000	0	-0.36	1	1
EnzymeConsortium:2.7.1.37	0.035	0.018	-10000	0	-0.16	1	1
response to UV	0	0	-10000	0	-0.002	1	1
RAF1	0.027	0.018	-10000	0	-0.16	2	2
CRADD	0.011	0	-10000	0	-10000	0	0
mol:ceramide	0.018	0.014	-10000	0	-0.13	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0.015	0	-10000	0	-10000	0	0
MADD	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.023	0.014	-10000	0	-0.12	1	1
TRADD	0.011	0	-10000	0	-10000	0	0
RELA/p50	0.011	0	-10000	0	-10000	0	0
MAPK3	0.033	0.017	-10000	0	-0.16	1	1
MAPK1	0.033	0.017	-10000	0	-0.16	1	1
p50/RELA/I-kappa-B-alpha	0.016	0	-10000	0	-10000	0	0
FADD	0.032	0.038	-10000	0	-0.38	1	1
KSR1	0.023	0.018	-10000	0	-0.16	3	3
MAPK8	0.03	0.024	-10000	0	-0.15	6	6
TRAF2	0.011	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.037	0.037	-10000	0	-0.36	1	1
TNF R/SODD	0.015	0.022	-10000	0	-0.28	3	3
TNF	-0.031	0.11	-10000	0	-0.33	68	68
CYCS	0.032	0.03	0.12	47	-0.11	1	48
IKBKG	0.037	0.037	-10000	0	-0.36	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.028	0.04	-10000	0	-0.25	8	8
RELA	0.011	0	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AIFM1	0.032	0.03	0.12	47	-0.11	1	48
TNF/TNF R/SODD	-0.003	0.067	-10000	0	-0.18	71	71
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.023	0.011	-10000	0	-10000	0	0
NSMAF	0.032	0.038	-10000	0	-0.37	1	1
response to hydrogen peroxide	0	0	-10000	0	-0.002	1	1
BCL2	-0.028	0.12	-10000	0	-0.41	50	50

×

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

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.009	0.031	-9999	-0.41	3	3
Caspase 8 (4 units)	0.031	0.034	-9999	-0.36	1	1
NEF	0.001	0.019	-9999	-0.16	4	4
NFKBIA	0.012	0.012	-9999	-10000	0	0
BIRC3	0.027	0.06	-9999	-0.4	10	10
CYCS	0.035	0.036	-9999	-0.25	4	4
RIPK1	0.011	0	-9999	-10000	0	0
CD247	0.01	0.036	-9999	-0.41	3	3
MAP2K7	0.037	0.034	-9999	-0.36	1	1
protein ubiquitination	0.049	0.026	-9999	-10000	0	0
CRADD	0.011	0	-9999	-10000	0	0
DAXX	0.011	0	-9999	-10000	0	0
FAS	0.007	0.04	-9999	-0.41	5	5
BID	0.031	0.038	-9999	-0.26	4	4
NF-kappa-B/RelA/I kappa B alpha	0.027	0.034	-9999	-0.22	9	9
TRADD	0.011	0	-9999	-10000	0	0
MAP3K5	0.009	0.031	-9999	-0.41	3	3
CFLAR	0.011	0	-9999	-10000	0	0
FADD	0.011	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.027	0.035	-9999	-0.22	9	9
MAPK8	0.039	0.038	-9999	-0.29	2	2
APAF1	0.011	0	-9999	-10000	0	0
TRAF1	0.011	0	-9999	-10000	0	0
TRAF2	0.011	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.026	0.039	-9999	-0.22	11	11
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.044	0.03	-9999	-0.24	2	2
CHUK	0.05	0.028	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.03	0.026	-9999	-10000	0	0
TCRz/NEF	0.01	0.039	-9999	-0.22	14	14
TNF	-0.032	0.11	-9999	-0.33	68	68
FASLG	0.013	0.061	-9999	-0.34	14	14
NFKB1	0.011	0.021	-9999	-0.4	1	1
TNFR1A/BAG4/TNF-alpha	-0.003	0.067	-9999	-0.18	71	71
CASP6	-0.003	0.022	-9999	-10000	0	0
CASP7	0.057	0.068	-9999	-0.44	8	8
RELA	0.012	0.012	-9999	-10000	0	0
CASP2	0.011	0	-9999	-10000	0	0
CASP3	0.057	0.068	-9999	-0.44	8	8
TNFRSF1A	0.011	0	-9999	-10000	0	0
TNFR1A/BAG4	0.015	0.022	-9999	-0.28	3	3
CASP8	0.011	0	-9999	-10000	0	0
CASP9	0.011	0	-9999	-10000	0	0
MAP3K14	0.047	0.029	-9999	-10000	0	0
APAF-1/Caspase 9	-0.007	0.039	-9999	-0.28	9	9
BCL2	0.026	0.067	-9999	-0.29	6	6

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.024	0.013	-10000	0	-0.19	2	2
epithelial cell differentiation	-0.001	0.011	-10000	0	-0.18	2	2
CYFIP2	0.009	0.031	-10000	0	-0.41	3	3
ENAH	0.048	0.018	-10000	0	-10000	0	0
EGFR	0	0.066	-10000	0	-0.4	14	14
EPHA2	0.011	0	-10000	0	-10000	0	0
MYO6	0.029	0.012	-10000	0	-0.17	2	2
CTNNB1	0.011	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.021	0.019	-10000	0	-0.23	3	3
AQP5	0.013	0.051	-10000	0	-0.38	8	8
CTNND1	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.029	0.012	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.023	0.038	-10000	0	-0.18	18	18
EGF	-0.006	0.073	-10000	0	-0.34	25	25
NCKAP1	0.011	0	-10000	0	-10000	0	0
AQP3	-0.004	0.043	-10000	0	-0.45	5	5
cortical microtubule organization	-0.001	0.011	-10000	0	-0.18	2	2
GO:0000145	0.027	0.011	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.025	0.013	-10000	0	-0.19	2	2
MLLT4	0.011	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.013	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.027	0.017	-10000	0	-0.2	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.037	0.012	-10000	0	-10000	0	0
PVRL2	0.011	0	-10000	0	-10000	0	0
ZYX	0.029	0.012	-10000	0	-10000	0	0
ARF6/GTP	0.03	0.016	-10000	0	-10000	0	0
CDH1	0.009	0.025	-10000	0	-0.41	2	2
EGFR/EGFR/EGF/EGF	-0.01	0.041	-10000	0	-0.32	3	3
RhoA/GDP	-0.001	0.01	-10000	0	-10000	0	0
actin cytoskeleton organization	0.033	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer	-0.005	0.081	-10000	0	-0.41	21	21
GIT1	0.011	0	-10000	0	-10000	0	0
IGF1R	-0.005	0.081	-10000	0	-0.41	21	21
IGF1	-0.067	0.16	-10000	0	-0.41	101	101
DIAPH1	-0.003	0.039	-10000	0	-0.52	3	3
Wnt receptor signaling pathway	0.001	0.011	0.18	2	-10000	0	2
RHOA	0.011	0	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.012	-10000	0	-10000	0	0
CTNNA1	0.011	0	-10000	0	-10000	0	0
VCL	0.033	0.012	-10000	0	-10000	0	0
EFNA1	0.01	0.021	-10000	0	-0.33	2	2
LPP	0.034	0.012	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.001	0.012	-10000	0	-10000	0	0
SEC6/SEC8	-0.001	0.009	-10000	0	-10000	0	0
MGAT3	0.023	0.039	-10000	0	-0.18	18	18
HGF/MET	-0.036	0.073	-10000	0	-0.47	3	3
HGF	-0.076	0.17	-10000	0	-0.41	112	112
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.024	0.013	-10000	0	-0.2	2	2
actin cable formation	0.062	0.017	-10000	0	-10000	0	0
KIAA1543	0.033	0.025	-10000	0	-0.35	2	2
KIFC3	0.029	0.012	-10000	0	-10000	0	0
NCK1	0.009	0.025	-10000	0	-0.41	2	2
EXOC3	0.011	0	-10000	0	-10000	0	0
ACTN1	0.029	0.012	-10000	0	-10000	0	0
NCK1/GIT1	0.015	0.018	-10000	0	-0.28	2	2
mol:GDP	-0.001	0.011	-10000	0	-0.18	2	2
EXOC4	0.011	0	-10000	0	-10000	0	0
STX4	0.029	0.012	-10000	0	-0.17	2	2
PIP5K1C	0.029	0.012	-10000	0	-10000	0	0
LIMA1	0.011	0	-10000	0	-10000	0	0
ABI1	0.011	0	-10000	0	-10000	0	0
ROCK1	0.047	0.016	-10000	0	-10000	0	0
adherens junction assembly	0.045	0.026	-10000	0	-0.36	2	2
IGF-1R heterotetramer/IGF1	-0.037	0.078	-10000	0	-0.35	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0	-10000	0	-10000	0	0
MET	0.005	0.049	-10000	0	-0.37	9	9
PLEKHA7	0.029	0.015	-10000	0	-10000	0	0
mol:GTP	0.026	0.017	-10000	0	-0.2	2	2
establishment of epithelial cell apical/basal polarity	0.047	0.011	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.024	0.013	-10000	0	-0.19	2	2
regulation of cell-cell adhesion	0.033	0.012	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.024	0.013	-10000	0	-0.2	2	2

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.2	0.21	-10000	0	-0.41	266	266
CLTC	0.026	0.001	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.021	0.006	-10000	0	-10000	0	0
Dynamin 2/GTP	0.02	0	-10000	0	-10000	0	0
EXOC4	0.011	0	-10000	0	-10000	0	0
CD59	0.023	0.001	-10000	0	-10000	0	0
CPE	-0.01	0.075	-10000	0	-0.24	54	54
CTNNB1	0.011	0	-10000	0	-10000	0	0
membrane fusion	0.021	0.006	-10000	0	-10000	0	0
CTNND1	0.025	0	-10000	0	-10000	0	0
DNM2	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.026	0.003	-10000	0	-10000	0	0
TSHR	0.005	0.041	-10000	0	-0.19	23	23
INS	0.01	0.002	-10000	0	-10000	0	0
BIN1	0.008	0.036	-10000	0	-0.41	4	4
mol:Choline	0.021	0.006	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0.02	0	-10000	0	-10000	0	0
JUP	0.023	0.008	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.02	0.019	-10000	0	-0.2	4	4
ARF6/GTP	0.008	0	-10000	0	-10000	0	0
CDH1	0.022	0.011	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.008	0	-10000	0	-10000	0	0
MAPK8IP3	0.011	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0.008	0	-10000	0	-10000	0	0
EXOC2	0.011	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.035	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.011	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0.006	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.015	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.015	0	-10000	0	-10000	0	0
ACAP1	0.02	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.019	0.012	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.03	0.004	-10000	0	-10000	0	0
JIP4/KLC1	0.021	0	-10000	0	-10000	0	0
EXOC1	0.011	0	-10000	0	-10000	0	0
exocyst	0.035	0	-10000	0	-10000	0	0
RALA/GTP	0.008	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.015	0	-10000	0	-10000	0	0
receptor recycling	0.008	0	-10000	0	-10000	0	0
CTNNA1	0.025	0	-10000	0	-10000	0	0
NME1	0.015	0	-10000	0	-10000	0	0
clathrin coat assembly	0.026	0.002	-10000	0	-10000	0	0
IL2RA	0.02	0.015	-10000	0	-10000	0	0
VAMP3	0.015	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.075	0.076	-10000	0	-10000	0	0
EXOC6	0.011	0	-10000	0	-10000	0	0
PLD1	0.018	0	-10000	0	-10000	0	0
PLD2	0.017	0.011	-10000	0	-0.24	1	1
EXOC5	0.011	0	-10000	0	-10000	0	0
PIP5K1C	0.026	0.001	-10000	0	-10000	0	0
SDC1	0.003	0.032	-10000	0	-10000	0	0
ARF6/GDP	0.015	0	-10000	0	-10000	0	0
EXOC7	0.011	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0.006	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.021	0.006	-10000	0	-10000	0	0
endocytosis	-0.019	0.019	0.2	4	-10000	0	4
SCAMP2	0.011	0	-10000	0	-10000	0	0
ADRB2	-0.004	0.075	-10000	0	-10000	0	0
EXOC3	0.011	0	-10000	0	-10000	0	0
ASAP2	0.011	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.021	0	-10000	0	-10000	0	0
KLC1	0.011	0	-10000	0	-10000	0	0
AVPR2	-0.031	0.091	-10000	0	-10000	0	0
RALA	0.011	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0.005	-10000	0	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.058	0.035	-9999	-10000	0	0
ERC1	0.011	0	-9999	-10000	0	0
RIP2/NOD2	0.015	0.016	-9999	-0.25	2	2
NFKBIA	0.036	0.01	-9999	-10000	0	0
BIRC2	0.011	0	-9999	-10000	0	0
IKBKB	0.011	0	-9999	-10000	0	0
RIPK2	0.011	0	-9999	-10000	0	0
IKBKG	0.037	0.009	-9999	-10000	0	0
IKK complex/A20	-0.012	0.032	-9999	-10000	0	0
NEMO/A20/RIP2	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
NEMO/ATM	0.041	0.008	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.015	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.005	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.022	0	-9999	-10000	0	0
NOD2	0.01	0.023	-9999	-0.37	2	2
NFKB1	0.013	0.018	-9999	-0.4	1	1
RELA	0.014	0	-9999	-10000	0	0
MALT1	0.011	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.016	0	-9999	-10000	0	0
ATM	0.011	0	-9999	-10000	0	0
TNF/TNFR1A	-0.013	0.078	-9999	-0.22	68	68
TRAF6	0.011	0	-9999	-10000	0	0
PRKCA	-0.017	0.1	-9999	-0.41	36	36
CHUK	0.011	0	-9999	-10000	0	0
UBE2D3	0.011	0	-9999	-10000	0	0
TNF	-0.032	0.11	-9999	-0.33	68	68
NF kappa B1 p50/RelA	0.031	0.011	-9999	-0.22	1	1
BCL10	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.009	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
IKK complex	0.046	0.008	-9999	-10000	0	0
CYLD	0.011	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.009	0.035	-9999	-10000	0	0

×

PLK2 and PLK4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.01	0.018	-9999	-0.41	1	1
PLK4	0.007	0.035	-9999	-0.33	6	6
regulation of centriole replication	0.015	0.028	-9999	-0.23	7	7

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.007	0.04	-10000	0	-0.37	6	6
positive regulation of NF-kappaB transcription factor activity	0.006	0.053	-10000	0	-0.27	19	19
MAP2K4	0.035	0.02	-10000	0	-10000	0	0
IKBKB	0.011	0	-10000	0	-10000	0	0
TNFRSF10B	0.011	0	-10000	0	-10000	0	0
TNFRSF10A	0.009	0.025	-10000	0	-0.41	2	2
SMPD1	0.014	0.015	-10000	0	-0.16	3	3
IKBKG	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.001	0.064	-10000	0	-0.41	13	13
TRAIL/TRAILR2	0.013	0.028	-10000	0	-0.25	6	6
TRAIL/TRAILR3	0.013	0.031	-10000	0	-0.25	7	7
TRAIL/TRAILR1	0.012	0.033	-10000	0	-0.26	8	8
TRAIL/TRAILR4	0.006	0.053	-10000	0	-0.27	19	19
TRAIL/TRAILR1/DAP3/GTP	0.018	0.025	-10000	0	-0.19	8	8
IKK complex	-0.001	0.007	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.008	0	-10000	0	-10000	0	0
MAPK3	0.015	0.028	-10000	0	-0.25	6	6
MAP3K1	0.031	0.019	-10000	0	-0.2	3	3
TRAILR4 (trimer)	0.001	0.064	-10000	0	-0.41	13	13
TRADD	0.011	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.009	0.025	-10000	0	-0.41	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.028	0.022	-10000	0	-0.19	5	5
CFLAR	0.011	0	-10000	0	-10000	0	0
MAPK1	0.015	0.028	-10000	0	-0.25	6	6
TRAIL/TRAILR1/FADD/TRADD/RIP	0.03	0.024	-10000	0	-10000	0	0
mol:ceramide	0.014	0.015	-10000	0	-0.16	3	3
FADD	0.011	0	-10000	0	-10000	0	0
MAPK8	0.037	0.028	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.01	0.018	-10000	0	-0.41	1	1
CHUK	0.011	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.019	0.028	-10000	0	-0.21	8	8
DAP3	0.011	0	-10000	0	-10000	0	0
CASP10	0.002	0.046	0.22	13	-0.31	4	17
JNK cascade	0.006	0.053	-10000	0	-0.27	19	19
TRAIL (trimer)	0.007	0.04	-10000	0	-0.37	6	6
TNFRSF10C	0.01	0.018	-10000	0	-0.41	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	0.023	0.024	-10000	0	-0.19	5	5
TRAIL/TRAILR2/FADD	0.02	0.023	-10000	0	-0.23	3	3
cell death	0.014	0.015	-10000	0	-0.16	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.028	0.017	-10000	0	-0.19	3	3
TRAILR2 (trimer)	0.011	0	-10000	0	-10000	0	0
CASP8	0.001	0.009	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.031	0.02	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	0.002	0.023	0.21	6	-10000	0	6
DAPP1	0.028	0.042	-10000	0	-0.3	3	3
Src family/SYK family/BLNK-LAT/BTK-ITK	0.045	0.046	-10000	0	-0.49	1	1
mol:DAG	0.046	0.031	0.16	5	-0.18	1	6
HRAS	0.012	0.001	-10000	0	-10000	0	0
RAP1A	0.012	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.027	0.046	-10000	0	-0.2	13	13
PLCG2	0.01	0.023	-10000	0	-0.37	2	2
PLCG1	0.011	0	-10000	0	-10000	0	0
ARF5	0.011	0	-10000	0	-10000	0	0
mol:GTP	0.002	0.023	0.2	6	-10000	0	6
ARF1/GTP	0.002	0.023	0.21	6	-10000	0	6
RHOA	0.011	0	-10000	0	-10000	0	0
YES1	0.011	0	-10000	0	-10000	0	0
RAP1A/GTP	0.023	0.02	0.2	6	-10000	0	6
ADAP1	0.002	0.022	0.2	6	-10000	0	6
ARAP3	0.002	0.023	0.2	6	-10000	0	6
INPPL1	0.011	0	-10000	0	-10000	0	0
PREX1	0.011	0	-10000	0	-10000	0	0
ARHGEF6	0	0.067	-10000	0	-0.41	14	14
ARHGEF7	0.011	0	-10000	0	-10000	0	0
ARF1	0.011	0	-10000	0	-10000	0	0
NRAS	0.012	0.001	-10000	0	-10000	0	0
FYN	0.011	0	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
FGR	0.002	0.059	-10000	0	-0.41	11	11
mol:Ca2+	0.032	0.018	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0	0.067	-10000	0	-0.41	14	14
ZAP70	-0.001	0.063	-10000	0	-0.34	18	18
mol:IP3	0.039	0.023	-10000	0	-10000	0	0
LYN	0.011	0	-10000	0	-10000	0	0
ARF1/GDP	0.027	0.046	-10000	0	-0.32	3	3
RhoA/GDP	0	0.025	0.19	6	-0.2	1	7
PDK1/Src/Hsp90	0.022	0	-10000	0	-10000	0	0
BLNK	0.009	0.029	-10000	0	-0.38	3	3
actin cytoskeleton reorganization	0.046	0.036	0.21	4	-0.23	3	7
SRC	0.011	0	-10000	0	-10000	0	0
PLEKHA2	0.023	0.011	-10000	0	-0.23	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
PTEN	0.003	0.041	-10000	0	-0.39	6	6
HSP90AA1	0.011	0	-10000	0	-10000	0	0
ARF6/GTP	0.002	0.023	0.21	6	-10000	0	6
RhoA/GTP	0.028	0.02	0.2	6	-10000	0	6
Src family/SYK family/BLNK-LAT	0.035	0.039	-10000	0	-0.3	1	1
BLK	-0.015	0.087	-10000	0	-0.33	39	39
PDPK1	0.011	0	-10000	0	-10000	0	0
CYTH1	0.002	0.022	0.2	6	-10000	0	6
HCK	0.007	0.038	-10000	0	-0.33	7	7
CYTH3	0.002	0.022	0.2	6	-10000	0	6
CYTH2	0.002	0.022	0.2	6	-10000	0	6
KRAS	0.011	0.015	-10000	0	-0.33	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.035	0.029	-10000	0	-0.38	2	2
SGK1	0	0.031	0.16	6	-0.42	2	8
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	0.022	0.048	-10000	0	-0.22	13	13
SOS1	0.011	0	-10000	0	-10000	0	0
SYK	0.01	0.015	-10000	0	-0.33	1	1
ARF6/GDP	0	0.025	0.2	6	-0.21	1	7
mol:PI-3-4-5-P3	0.002	0.026	0.23	6	-10000	0	6
ARAP3/RAP1A/GTP	0.023	0.021	0.2	6	-10000	0	6
VAV1	0.007	0.037	-10000	0	-0.34	6	6
mol:PI-3-4-P2	0.018	0.013	-10000	0	-0.28	1	1
RAS family/GTP/PI3K Class I	0.025	0.01	-10000	0	-10000	0	0
PLEKHA1	0.023	0.011	-10000	0	-0.23	1	1
Rac1/GDP	0.027	0.046	-10000	0	-0.32	3	3
LAT	0.011	0	-10000	0	-10000	0	0
Rac1/GTP	0.019	0.067	-10000	0	-0.26	25	25
ITK	-0.002	0.034	0.2	6	-10000	0	6
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.053	0.038	0.18	5	-0.24	1	6
LCK	0.008	0.034	-10000	0	-0.34	5	5
BTK	0.001	0.025	0.2	6	-10000	0	6

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.012	0.032	-9999	-0.24	2	2
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.027	0.032	-9999	-0.24	2	2
SUMO1	0.011	0	-9999	-10000	0	0
ZFPM1	0.009	0.025	-9999	-0.41	2	2
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.011	0	-9999	-10000	0	0
Histones	0.028	0.025	-9999	-10000	0	0
YY1/LSF	0.018	0.04	-9999	-0.2	18	18
SMG5	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.015	0.035	-9999	-0.19	2	2
I kappa B alpha/HDAC1	0.016	0.027	-9999	-10000	0	0
SAP18	0.011	0	-9999	-10000	0	0
RELA	0.02	0.031	-9999	-0.19	4	4
HDAC1/Smad7	0.022	0.015	-9999	-0.23	2	2
RANGAP1	0.011	0	-9999	-10000	0	0
HDAC3/TR2	0.016	0.027	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.013	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.023	0.03	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.03	0.12	-9999	-0.41	53	53
GATA1	0.006	0.005	-9999	-10000	0	0
Mad/Max	0.016	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.044	0.017	-9999	-10000	0	0
RBBP7	0.011	0	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
RBBP4	0.009	0.031	-9999	-0.41	3	3
MAX	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.011	0	-9999	-10000	0	0
NFKBIA	0.012	0.031	-9999	-10000	0	0
KAT2B	0.004	0.054	-9999	-0.41	9	9
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.034	0.014	-9999	-10000	0	0
SIN3 complex	0.028	0	-9999	-10000	0	0
SMURF1	0.011	0	-9999	-10000	0	0
CHD3	0.011	0	-9999	-10000	0	0
SAP30	0.011	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.011	0	-9999	-10000	0	0
YY1/HDAC3	0.022	0.035	-9999	-10000	0	0
YY1/HDAC2	0.021	0.03	-9999	-0.19	11	11
YY1/HDAC1	0.021	0.03	-9999	-0.19	11	11
NuRD/MBD2 Complex (MeCP1)	0.037	0.013	-9999	-10000	0	0
PPARG	0.005	0.071	-9999	-0.26	31	31
HDAC8/hEST1B	0.022	0	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.016	0.027	-9999	-10000	0	0
MBD3L2	0.002	0.004	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.021	0.015	-9999	-0.23	2	2
CREBBP	0.009	0.025	-9999	-0.41	2	2
NuRD/MBD3/MBD3L2 Complex	0.041	0.013	-9999	-10000	0	0
HDAC1	0.011	0	-9999	-10000	0	0
HDAC3	0.012	0.031	-9999	-10000	0	0
HDAC2	0.011	0	-9999	-10000	0	0
YY1	0.019	0.036	-9999	-0.23	11	11
HDAC8	0.011	0	-9999	-10000	0	0
SMAD7	0.009	0.025	-9999	-0.41	2	2
NCOR2	0.011	0	-9999	-10000	0	0
MXD1	0.011	0	-9999	-10000	0	0
STAT3	0.02	0.017	-9999	-0.27	2	2
NFKB1	0.01	0.018	-9999	-0.41	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.011	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.024	0.037	-9999	-0.18	18	18
YY1/SAP30/HDAC1	0.026	0.028	-9999	-0.17	11	11
EP300	0.011	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0.017	-9999	-0.27	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.031	-9999	-10000	0	0
histone deacetylation	0.037	0.013	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.023	0.028	-9999	-10000	0	0
nuclear export	-0.022	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GATAD2B	0.011	0	-9999	-10000	0	0
GATAD2A	0.011	0	-9999	-10000	0	0
GATA2/HDAC3	-0.005	0.074	-9999	-0.21	53	53
GATA1/HDAC1	0.013	0.004	-9999	-10000	0	0
GATA1/HDAC3	0.005	0.027	-9999	-10000	0	0
CHD4	0.011	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.013	0.078	-9999	-0.22	68	68
SIN3/HDAC complex/Mad/Max	0.037	0.013	-9999	-10000	0	0
NuRD Complex	0.044	0.013	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.024	-9999	-10000	0	0
SIN3B	0.011	0	-9999	-10000	0	0
MTA2	0.011	0	-9999	-10000	0	0
SIN3A	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
SUMO1/HDAC1	0.025	0	-9999	-10000	0	0
HDAC complex	0.027	0.017	-9999	-0.2	3	3
GATA1/Fog1	0.012	0.018	-9999	-0.28	2	2
FKBP25/HDAC1/HDAC2	0.022	0	-9999	-10000	0	0
TNF	-0.032	0.11	-9999	-0.33	68	68
negative regulation of cell growth	0.037	0.013	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.037	0.013	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.027	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.023	0.032	-9999	-0.25	2	2
SIN3/HDAC complex/NCoR1	0.035	0.014	-9999	-10000	0	0
TFCP2	0.006	0.047	-9999	-0.41	7	7
NR2C1	0.011	0	-9999	-10000	0	0
MBD3	0.011	0	-9999	-10000	0	0
MBD2	0.011	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.027	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.018	0	-9999	-10000	0	0
mol:DAG	0.031	0.007	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.024	0	-9999	-10000	0	0
CaM/Ca2+	0.035	0.007	-9999	-10000	0	0
HIF1A	0.018	0	-9999	-10000	0	0
GAB1	0.008	0.036	-9999	-0.41	4	4
AKT1	0.043	0.026	-9999	-10000	0	0
PLCG1	0.031	0.007	-9999	-10000	0	0
NOS3	0.048	0.017	-9999	-0.25	1	1
CBL	0.011	0	-9999	-10000	0	0
mol:NO	0.048	0.017	-9999	-0.24	1	1
FLT1	0.025	0	-9999	-10000	0	0
PGF	0.01	0.015	-9999	-0.33	1	1
VEGFR1 homodimer/NRP2/VEGFR121	0.021	0.047	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
eNOS/Hsp90	0.052	0.016	-9999	-0.23	1	1
endothelial cell proliferation	0.019	0.065	-9999	-0.31	4	4
mol:Ca2+	0.031	0.007	-9999	-10000	0	0
MAPK3	0.026	0.05	-9999	-10000	0	0
MAPK1	0.026	0.05	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
PLGF homodimer	0.01	0.015	-9999	-0.33	1	1
PRKACA	0.011	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.062	0.16	-9999	-0.41	94	94
VEGFA homodimer	0.011	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.027	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.031	0.049	-9999	-10000	0	0
PI3K	0.035	0.023	-9999	-10000	0	0
PRKCA	0.021	0.053	-9999	-10000	0	0
PRKCB	0.023	0.05	-9999	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	0.026	0.008	-9999	-10000	0	0
VEGFA	0.011	0	-9999	-10000	0	0
VEGFB	0.011	0	-9999	-10000	0	0
mol:IP3	0.031	0.007	-9999	-10000	0	0
RASA1	0.03	0.022	-9999	-10000	0	0
NRP2	-0.008	0.088	-9999	-0.41	25	25
VEGFR1 homodimer	0.025	0	-9999	-10000	0	0
VEGFB homodimer	0.011	0	-9999	-10000	0	0
NCK1	0.009	0.025	-9999	-0.41	2	2
eNOS/Caveolin-1	0.02	0.074	-9999	-0.41	1	1
PTPN11	0.011	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.033	0.023	-9999	-10000	0	0
mol:L-citrulline	0.048	0.017	-9999	-0.24	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.037	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.031	0.014	-9999	-10000	0	0
CD2AP	0.011	0	-9999	-10000	0	0
PI3K/GAB1	0.037	0.028	-9999	-10000	0	0
PDPK1	0.037	0.022	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.032	0	-9999	-10000	0	0
mol:NADP	0.048	0.017	-9999	-0.24	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.036	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.015	0.052	-9999	-0.22	25	25

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.01	0.018	-9999	-0.41	1	1
SMAD2	0.011	0	-9999	-10000	0	0
SMAD3	0.031	0.017	-9999	-10000	0	0
SMAD3/SMAD4	0.036	0.019	-9999	-0.33	1	1
SMAD4/Ubc9/PIASy	0.022	0.011	-9999	-0.23	1	1
SMAD2/SMAD2/SMAD4	0.025	0.033	-9999	-10000	0	0
PPM1A	0.011	0	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
SMAD2/SMAD4	0.017	0.009	-9999	-0.2	1	1
MAP3K1	0.011	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.011	0.038	-9999	-0.28	9	9
MAPK3	0.011	0	-9999	-10000	0	0
MAPK1	0.011	0	-9999	-10000	0	0
NUP214	0.011	0	-9999	-10000	0	0
CTDSP1	0.011	0	-9999	-10000	0	0
CTDSP2	0.011	0	-9999	-10000	0	0
CTDSPL	0.011	0	-9999	-10000	0	0
KPNB1	0.011	0	-9999	-10000	0	0
TGFBRAP1	0.005	0.051	-9999	-0.41	8	8
UBE2I	0.011	0	-9999	-10000	0	0
NUP153	0.01	0.018	-9999	-0.41	1	1
KPNA2	-0.005	0.071	-9999	-0.33	25	25
PIAS4	0.011	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.011	0	-9999	-10000	0	0
ITGB7	0.01	0.015	-9999	-0.33	1	1
ITGA4	0.009	0.029	-9999	-0.38	3	3
alpha4/beta7 Integrin	0.014	0.023	-9999	-0.25	4	4
alpha4/beta1 Integrin	0.015	0.021	-9999	-0.26	3	3

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.011	0	-10000	0	-10000	0	0
Rac1/GDP	0	0.003	-10000	0	-10000	0	0
DOCK1	0.006	0.047	-10000	0	-0.41	7	7
ITGA4	0.009	0.029	-10000	0	-0.38	3	3
RAC1	0.011	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.014	0.023	-10000	0	-0.25	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.021	0.017	-10000	0	-0.21	3	3
alpha4/beta7 Integrin/Paxillin	0.026	0.017	-10000	0	-0.2	2	2
lamellipodium assembly	-0.006	0.047	-10000	0	-0.4	6	6
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
PI3K	0.013	0.031	-10000	0	-0.28	6	6
ARF6	0.011	0	-10000	0	-10000	0	0
TLN1	0.011	0	-10000	0	-10000	0	0
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.04	-10000	0	-0.41	5	5
ARF6/GTP	-0.001	0.011	-10000	0	-10000	0	0
cell adhesion	0.031	0.014	-10000	0	-0.18	2	2
CRKL/CBL	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.026	0.016	-10000	0	-0.2	2	2
ITGB1	0.011	0	-10000	0	-10000	0	0
ITGB7	0.01	0.015	-10000	0	-0.33	1	1
ARF6/GDP	0	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.016	0.06	-10000	0	-0.38	2	2
p130Cas/Crk/Dock1	0.019	0.028	-10000	0	-0.23	7	7
VCAM1	-0.02	0.11	-10000	0	-0.41	40	40
alpha4/beta1 Integrin/Paxillin/Talin	0.032	0.015	-10000	0	-0.18	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.032	0.015	-10000	0	-0.18	2	2
BCAR1	0.011	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.014	0.18	2	-10000	0	2
CBL	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0	-10000	0	-10000	0	0
GIT1	0.011	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.032	0.015	-10000	0	-0.18	2	2
Rac1/GTP	-0.007	0.053	-10000	0	-0.44	6	6

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.036	0.03	-10000	0	-0.22	7	7
adherens junction organization	0.033	0.028	-10000	0	-0.35	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.037	0.041	-10000	0	-0.38	2	2
FMN1	0.027	0.038	-10000	0	-0.34	2	2
mol:IP3	0.031	0.026	-10000	0	-0.29	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.027	-10000	0	-0.36	2	2
CTNNB1	0.011	0.001	-10000	0	-10000	0	0
AKT1	0.036	0.027	-10000	0	-0.33	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.033	0.028	-10000	0	-0.42	2	2
CTNND1	0.012	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.033	0.025	-10000	0	-0.33	2	2
VASP	0.033	0.025	-10000	0	-0.34	2	2
ZYX	0.033	0.025	-10000	0	-0.34	2	2
JUB	0.033	0.025	-10000	0	-0.34	2	2
EGFR(dimer)	0.028	0.044	-10000	0	-0.36	3	3
E-cadherin/beta catenin-gamma catenin	-0.001	0.02	-10000	0	-0.31	2	2
mol:PI-3-4-5-P3	0.03	0.028	-10000	0	-0.2	7	7
PIK3CA	0.011	0.018	-10000	0	-0.41	1	1
PI3K	0.031	0.028	-10000	0	-0.2	7	7
FYN	0.032	0.036	-10000	0	-0.24	1	1
mol:Ca2+	0.03	0.025	-10000	0	-0.29	1	1
JUP	0.01	0.018	-10000	0	-0.4	1	1
PIK3R1	0.008	0.04	-10000	0	-0.41	5	5
mol:DAG	0.031	0.026	-10000	0	-0.29	1	1
CDH1	0.009	0.025	-10000	0	-0.41	2	2
RhoA/GDP	0.037	0.041	-10000	0	-0.38	2	2
establishment of polarity of embryonic epithelium	0.033	0.025	-10000	0	-0.33	2	2
SRC	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
EGFR	0	0.066	-10000	0	-0.4	14	14
CASR	0.024	0.043	-10000	0	-0.27	1	1
RhoA/GTP	-0.002	0.019	-10000	0	-0.26	1	1
AKT2	0.036	0.027	-10000	0	-0.33	1	1
actin cable formation	0.032	0.036	-10000	0	-0.46	1	1
apoptosis	-0.034	0.028	0.2	7	-10000	0	7
CTNNA1	0.012	0.001	-10000	0	-10000	0	0
mol:GDP	0.032	0.043	-10000	0	-0.41	2	2
PIP5K1A	0.033	0.025	-10000	0	-0.34	2	2
PLCG1	0.031	0.026	-10000	0	-0.3	1	1
Rac1/GTP	-0.005	0.035	-10000	0	-0.41	2	2
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.033	0.015	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.008	-10000	0	-10000	0	0
myoblast fusion	-0.017	0.013	-10000	0	-10000	0	0
mol:GTP	-0.001	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.023	0.039	0.22	14	-10000	0	14
ARF1/GTP	0	0.003	-10000	0	-10000	0	0
mol:GM1	0.008	0.005	-10000	0	-10000	0	0
mol:Choline	0.022	0.011	-10000	0	-0.22	1	1
lamellipodium assembly	0.001	0.012	-10000	0	-10000	0	0
MAPK3	0.023	0.009	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.023	0.039	-10000	0	-0.22	14	14
ARF1	0.011	0	-10000	0	-10000	0	0
ARF6/GDP	0.017	0.013	-10000	0	-10000	0	0
ARF1/GDP	0.022	0.012	-10000	0	-10000	0	0
ARF6	0.01	0.003	-10000	0	-10000	0	0
RAB11A	0.011	0	-10000	0	-10000	0	0
TIAM1	0.002	0.067	-10000	0	-0.41	14	14
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.023	0.009	-10000	0	-10000	0	0
actin filament bundle formation	-0.02	0.01	-10000	0	-10000	0	0
KALRN	-0.001	0.023	-10000	0	-0.21	4	4
RAB11FIP3/RAB11A	0.016	0	-10000	0	-10000	0	0
RhoA/GDP	0.021	0.01	-10000	0	-10000	0	0
NME1	0.012	0.001	-10000	0	-10000	0	0
Rac1/GDP	0.021	0.01	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.001	0.005	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.001	0.012	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
liver development	-0.001	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.005	-10000	0	-10000	0	0
RhoA/GTP	0	0.003	-10000	0	-10000	0	0
mol:GDP	0.001	0.013	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.021	0.005	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
PLD1	0.017	0.005	-10000	0	-10000	0	0
RAB11FIP3	0.011	0	-10000	0	-10000	0	0
tube morphogenesis	0.001	0.012	-10000	0	-10000	0	0
ruffle organization	0.023	0.008	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.001	0.005	-10000	0	-10000	0	0
PLD2	0.017	0.013	-10000	0	-0.26	1	1
PIP5K1A	0.023	0.008	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.022	0.011	-10000	0	-0.22	1	1
Rac1/GTP	0.001	0.012	-10000	0	-10000	0	0

×

Atypical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.016	0.01	-9999	-0.22	1	1
FBXW11	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.021	0.011	-9999	-0.23	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.037	0.012	-9999	-10000	0	0
NFKBIA	0.023	0.01	-9999	-0.17	1	1
MAPK14	0.011	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0.011	-9999	-0.23	1	1
ARRB2	0.014	0	-9999	-10000	0	0
REL	0.011	0.001	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.021	0.014	-9999	-0.2	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0.011	-9999	-0.23	1	1
PIK3CA	0.01	0.018	-9999	-0.41	1	1
NF kappa B1 p50 dimer	0.016	0.013	-9999	-0.28	1	1
PIK3R1	0.007	0.04	-9999	-0.41	5	5
NFKB1	0.018	0.013	-9999	-0.28	1	1
RELA	0.011	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.028	0.012	-9999	-0.18	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.04	0.012	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
PI3K	0.013	0.031	-9999	-0.28	6	6
NF kappa B1 p50/RelA	0.028	0.012	-9999	-0.18	1	1
IKBKB	0.011	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
SYK	0.01	0.015	-9999	-0.33	1	1
I kappa B alpha/PIK3R1	0.025	0.022	-9999	-10000	0	0
cell death	0.039	0.012	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.021	0.011	-9999	-0.23	1	1
LCK	0.008	0.034	-9999	-0.34	5	5
BCL3	0.01	0.015	-9999	-0.33	1	1

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.032	0.025	-9999	-0.38	2	2
KLHL20	-0.002	0.013	-9999	-10000	0	0
CYFIP2	0.009	0.031	-9999	-0.41	3	3
Rac1/GDP	0.048	0.016	-9999	-10000	0	0
ENAH	0.032	0.028	-9999	-0.38	2	2
AP1M1	0.011	0	-9999	-10000	0	0
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.011	0	-9999	-10000	0	0
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	0	0.008	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.002	0.011	-9999	-0.13	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.027	0.016	-9999	-0.2	2	2
RAPGEF1	0.041	0.022	-9999	-0.32	2	2
CTNND1	0.011	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.027	0.026	-9999	-0.4	2	2
CRK	0.037	0.024	-9999	-0.35	2	2
E-cadherin/gamma catenin/alpha catenin	0.021	0.023	-9999	-0.34	2	2
alphaE/beta7 Integrin	0.016	0.01	-9999	-0.22	1	1
IQGAP1	0.011	0	-9999	-10000	0	0
NCKAP1	0.011	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.021	0	-9999	-10000	0	0
DLG1	0.032	0.025	-9999	-0.38	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.01	-9999	-10000	0	0
MLLT4	0.011	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.016	0.036	-9999	-0.2	14	14
PI3K	-0.001	0.012	-9999	-10000	0	0
ARF6	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.015	0.027	-9999	-0.4	2	2
TIAM1	0	0.067	-9999	-0.41	14	14
E-cadherin(dimer)/Ca2+	0.026	0.013	-9999	-0.19	2	2
AKT1	-0.001	0.007	-9999	-10000	0	0
PIK3R1	0.007	0.04	-9999	-0.41	5	5
CDH1	0.009	0.025	-9999	-0.41	2	2
RhoA/GDP	0.048	0.016	-9999	-0.21	2	2
actin cytoskeleton organization	0.034	0.016	-9999	-10000	0	0
CDC42/GDP	0.048	0.016	-9999	-0.21	2	2
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.019	0.021	-9999	-0.31	2	2
ITGB7	0.01	0.015	-9999	-0.33	1	1
RAC1	0.011	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.028	0.014	-9999	-0.2	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin	0.019	0.013	-9999	-0.19	2	2
mol:GDP	0.046	0.018	-9999	-0.24	2	2
CDC42/GTP/IQGAP1	0.015	0	-9999	-10000	0	0
JUP	0.01	0.018	-9999	-0.41	1	1
p120 catenin/RhoA/GDP	0.045	0.017	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.015	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.016	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.026	0.015	-9999	-0.13	3	3
NME1	0.011	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.032	0.026	-9999	-0.38	2	2
regulation of cell-cell adhesion	0	0.007	-9999	-10000	0	0
WASF2	-0.001	0.005	-9999	-10000	0	0
Rap1/GTP	-0.001	0.009	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.031	0.021	-9999	-0.38	1	1
CCND1	0.031	0.018	-9999	-0.15	3	3
VAV2	0.041	0.024	-9999	-0.35	2	2
RAP1/GDP	0.043	0.015	-9999	-10000	0	0
adherens junction assembly	0.032	0.026	-9999	-0.37	2	2
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.011	0	-9999	-10000	0	0
PIP5K1C	0.011	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.036	0.02	-9999	-0.36	1	1
E-cadherin/beta catenin	-0.001	0.018	-9999	-0.3	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.032	0.025	-9999	-0.38	2	2
PIK3CA	0.01	0.018	-9999	-0.41	1	1
Rac1/GTP	-0.003	0.018	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.022	0.015	-9999	-0.23	2	2
ITGAE	0.011	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.027	0.026	-9999	-0.4	2	2

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.021	0.023	-9999	-0.34	2	2
E-cadherin/beta catenin	0.015	0.018	-9999	-0.28	2	2
CTNNB1	0.011	0	-9999	-10000	0	0
JUP	0.01	0.018	-9999	-0.41	1	1
CDH1	0.009	0.025	-9999	-0.41	2	2

×

Circadian rhythm 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.039	0.011	-9999	-10000	0	0
CLOCK	0.014	0.001	-9999	-10000	0	0
TIMELESS/CRY2	0.034	0.011	-9999	-10000	0	0
DEC1/BMAL1	0.011	0.013	-9999	-0.28	1	1
ATR	0.011	0	-9999	-10000	0	0
NR1D1	0.033	0.009	-9999	-10000	0	0
ARNTL	0.013	0.018	-9999	-0.41	1	1
TIMELESS	0.033	0.013	-9999	-10000	0	0
NPAS2	0.01	0.04	-9999	-0.41	5	5
CRY2	0.011	0	-9999	-10000	0	0
mol:CO	-0.011	0.003	-9999	-10000	0	0
CHEK1	0.011	0	-9999	-10000	0	0
mol:HEME	0.011	0.003	-9999	-10000	0	0
PER1	0.009	0.031	-9999	-0.41	3	3
BMAL/CLOCK/NPAS2	0.033	0.027	-9999	-0.22	6	6
BMAL1/CLOCK	0.04	0.019	-9999	-10000	0	0
S phase of mitotic cell cycle	0.039	0.011	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.039	0.011	-9999	-10000	0	0
mol:NADPH	0.011	0.003	-9999	-10000	0	0
PER1/TIMELESS	0.033	0.02	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.001	0.004	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.011	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.025	-9999	-9999
HDAC4	0.011	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.011	-9999	-9999
NPC/RanGAP1/SUMO1	0.014	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.022	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.011	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.011	-9999	-9999
SUMO1/HDAC4	0.025	-9999	-9999
SUMO1/HDAC1	0.025	-9999	-9999
RANGAP1	0.011	-9999	-9999
MDM2/SUMO1/SUMO1	0.028	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	-9999	-9999
Ran/GTP	0.022	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.011	-9999	-9999
UBE2I	0.011	-9999	-9999
Ran/GTP/Exportin 1	0.027	-9999	-9999
NPC	0.007	-9999	-9999
PIAS2	0.011	-9999	-9999
PIAS1	0.011	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0.004	-9999	-10000	0	0
AP2	0.016	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.015	0	-9999	-10000	0	0
CLTB	0.011	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.021	0	-9999	-10000	0	0
CD4	0.01	0.015	-9999	-0.33	1	1
CLTA	0.011	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.006	-9999	-0.15	1	1
ARF1/GTP	0	0.003	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0	-9999	-10000	0	0
mol:Choline	0	0.006	-9999	-0.15	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.011	0	-9999	-10000	0	0
DDEF1	0	0.007	-9999	-0.16	1	1
ARF1/GDP	0	0.002	-9999	-10000	0	0
AP2M1	0.011	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.014	0	-9999	-10000	0	0
Rac/GTP	0.009	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.021	0	-9999	-10000	0	0
ARFIP2	0.01	0	-9999	-10000	0	0
COPA	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.02	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.008	0	-9999	-10000	0	0
GGA3	0.011	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.015	0.002	-9999	-10000	0	0
AP2A1	0.011	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.022	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.015	0.003	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.014	0	-9999	-10000	0	0
CYTH2	0.011	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.016	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.008	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.028	0.003	-9999	-10000	0	0
PLD2	0	0.007	-9999	-0.15	1	1
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0.006	-9999	-0.15	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.003	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.006	-9999	-0.15	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.016	0.001	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.022	0.008	-9999	-0.17	1	1

×

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	0.016	0	-9999	-10000	0	0
FBXW11	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
CHUK	0.011	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.033	0	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAP3K14	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.016	0.013	-9999	-0.28	1	1
RELB	0.011	0	-9999	-10000	0	0
NFKB2	0.011	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.015	0	-9999	-10000	0	0
regulation of B cell activation	0.015	0	-9999	-10000	0	0

pid_entity	TCGA.SL.A6JA	TCGA.SL.A6J9	TCGA.SJ.A6ZJ	TCGA.SJ.A6ZI
109_MAP3K5	-0.13	0.043	0.043	0.043
47_PPARGC1A	-0.41	0.011	0.011	-0.41
105_BMP4	0.011	-0.41	0.011	0.011
105_BMP6	0.011	0.011	0.011	0.011
105_BMP7	0.011	0.011	0.011	0.011
105_BMP2	0.011	-0.41	0.011	0.011
131_RELN/VLDLR	-0.2	-0.2	0.028	-0.2
30_TGFB1/TGF beta receptor Type II	0.011	0.011	0.013	0.01
84_STAT5B	-0.023	-0.091	-0.024	0.038
84_STAT5A	-0.023	-0.091	-0.024	0.038