Ovarian Serous Cystadenocarcinoma: PARADIGM pathway analysis of mRNA expression and copy number data
Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/Harvard Medical School)
Overview
Introduction

PAthway Representation and Analysis by Direct Inference on Graphical Models (PARADIGM) predicts the activity of a diverse set of molecular concepts such as genes, complexes, and processes. The predicted activities are called Inferred Pathway Levels (IPLs) and are derived from a probabilistic belief propagation strategy that incorporates multimodal data such as copy number and gene expression estimates with a concept's pathway context.

Summary

There were 103 significant pathways identified in this analysis.

Table 1.  Get Full Table Top 10 out of 131 pathways in order of significance.

Pathway.Name Avg.Num.Perturbations
PLK2 and PLK4 events 177
FOXM1 transcription factor network 137
TCGA08_p53 99
HIF-1-alpha transcription factor network 94
Ephrin B reverse signaling 93
LPA receptor mediated events 90
Endothelins 88
Syndecan-1-mediated signaling events 87
Osteopontin-mediated events 86
Wnt signaling 84
Results

The following list describes the columns found in Table 2.

  • Pathway.Name = Full pathway name of curated PARADIGM pathway

  • Avg.Num.Perturbations = Average number of samples with perturbations across the pathway concepts determined by a background permutation model (>2 standard deviations away from the permuted distribution)

  • Total.Perturbations = Total number of perturbed concepts across all samples (>2 standard deviations away from the permuted distribution)

  • Num.Entities = Number of concepts that belong to the pathway

  • Min.Mean.Truth = Minimum IPL for concepts in the pathway among real samples

  • Max.Mean.Truth = Maximum IPL for concepts in the pathway among real samples

  • Min.Mean.Within = Minimum IPL for concepts in the pathway among null samples using "within permutation" (values are permuted across genes)

  • Max.Mean.Within = Maximum IPL for concepts in the pathway among null samples using "within permutation" (values are permuted across genes)

  • Min.Mean.Any = Minimum IPL for concepts in the pathway among null samples using "any permutation" (values are permuted across samples and genes)

  • Max.Mean.Any = Maximum IPL for concepts in the pathway among null samples using "any permutation" (values are permuted across samples and genes).

Table 2.  Get Full Table This summary table provides a report of cancer type specific pathway perturbations. Click on the links in the first column to display more detailed results for each pathway.

Pathway.Name 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
PLK2 and PLK4 events 177 532 3 -0.011 0.036 1000 -1000 -0.017 -1000
FOXM1 transcription factor network 137 7014 51 -0.51 0.037 1000 -1000 -0.014 -1000
TCGA08_p53 99 694 7 -0.053 0.038 1000 -1000 -0.009 -1000
HIF-1-alpha transcription factor network 94 7178 76 -0.048 0.087 1000 -1000 0 -1000
Ephrin B reverse signaling 93 4483 48 -0.2 0.079 1000 -1000 -0.051 -1000
LPA receptor mediated events 90 9236 102 -0.043 0.04 1000 -1000 -0.04 -1000
Endothelins 88 8532 96 -0.18 0.04 1000 -1000 -0.021 -1000
Syndecan-1-mediated signaling events 87 2963 34 -0.044 0.04 1000 -1000 -0.003 -1000
Osteopontin-mediated events 86 3294 38 -0.19 0.04 1000 -1000 -0.008 -1000
Wnt signaling 84 592 7 -0.017 0.04 1000 -1000 -0.003 -1000
Nectin adhesion pathway 81 5104 63 -0.088 0.063 1000 -1000 -0.012 -1000
amb2 Integrin signaling 79 6520 82 -0.085 0.081 1000 -1000 -0.016 -1000
PDGFR-alpha signaling pathway 78 3441 44 -0.13 0.049 1000 -1000 -0.022 -1000
TCGA08_retinoblastoma 78 626 8 -0.012 0.03 1000 -1000 -0.004 -1000
Thromboxane A2 receptor signaling 76 8047 105 -0.15 0.069 1000 -1000 -0.02 -1000
TRAIL signaling pathway 74 3597 48 -0.02 0.041 1000 -1000 -0.017 -1000
BARD1 signaling events 72 4124 57 -0.039 0.06 1000 -1000 -0.065 -1000
TCGA08_rtk_signaling 71 1857 26 -0.021 0.039 1000 -1000 -0.02 -1000
Paxillin-dependent events mediated by a4b1 70 2539 36 -0.065 0.067 1000 -1000 -0.052 -1000
Nongenotropic Androgen signaling 69 3630 52 -0.12 0.059 1000 -1000 -0.018 -1000
Signaling events mediated by the Hedgehog family 67 3520 52 -0.066 0.058 1000 -1000 -0.024 -1000
Integrins in angiogenesis 67 5644 84 -0.053 0.054 1000 -1000 -0.017 -1000
Ras signaling in the CD4+ TCR pathway 67 1154 17 -0.007 0.053 1000 -1000 -0.003 -1000
IL1-mediated signaling events 66 4143 62 -0.045 0.072 1000 -1000 -0.017 -1000
IL23-mediated signaling events 66 4018 60 -0.17 0.049 1000 -1000 -0.039 -1000
Signaling events mediated by PTP1B 65 4974 76 -0.059 0.068 1000 -1000 -0.036 -1000
IGF1 pathway 65 3707 57 -0.022 0.065 1000 -1000 -0.016 -1000
IL12-mediated signaling events 64 5608 87 -0.18 0.053 1000 -1000 -0.022 -1000
Fc-epsilon receptor I signaling in mast cells 64 6243 97 -0.081 0.046 1000 -1000 -0.038 -1000
Cellular roles of Anthrax toxin 63 2482 39 -0.082 0.04 1000 -1000 -0.015 -1000
Canonical Wnt signaling pathway 63 3228 51 -0.18 0.092 1000 -1000 -0.011 -1000
Syndecan-4-mediated signaling events 63 4246 67 -0.064 0.043 1000 -1000 -0.031 -1000
Syndecan-2-mediated signaling events 60 4183 69 -0.004 0.062 1000 -1000 -0.013 -1000
IL6-mediated signaling events 60 4553 75 -0.14 0.049 1000 -1000 -0.019 -1000
E-cadherin signaling in keratinocytes 60 2584 43 -0.017 0.052 1000 -1000 -0.007 -1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met) 59 5041 85 -0.16 0.049 1000 -1000 -0.028 -1000
IL4-mediated signaling events 59 5408 91 -0.22 0.055 1000 -1000 -0.034 -1000
IL2 signaling events mediated by STAT5 59 1307 22 -0.036 0.047 1000 -1000 -0.006 -1000
a4b1 and a4b7 Integrin signaling 58 294 5 0.031 0.038 1000 -1000 0.037 -1000
FoxO family signaling 58 3748 64 -0.2 0.044 1000 -1000 -0.019 -1000
Noncanonical Wnt signaling pathway 57 1491 26 -0.036 0.04 1000 -1000 -0.038 -1000
HIF-2-alpha transcription factor network 57 2459 43 -0.056 0.069 1000 -1000 -0.079 -1000
TCR signaling in naïve CD8+ T cells 57 5348 93 -0.071 0.076 1000 -1000 -0.027 -1000
BMP receptor signaling 56 4600 81 -0.021 0.071 1000 -1000 -0.001 -1000
IFN-gamma pathway 54 3685 68 -0.045 0.062 1000 -1000 -0.031 -1000
Retinoic acid receptors-mediated signaling 54 3167 58 -0.084 0.061 1000 -1000 -0.003 -1000
Plasma membrane estrogen receptor signaling 54 4644 86 -0.086 0.083 1000 -1000 -0.018 -1000
Paxillin-independent events mediated by a4b1 and a4b7 53 1995 37 -0.019 0.069 1000 -1000 -0.01 -1000
EPHB forward signaling 53 4508 85 -0.057 0.14 1000 -1000 -0.038 -1000
FAS signaling pathway (CD95) 51 2431 47 -0.042 0.053 1000 -1000 -0.024 -1000
BCR signaling pathway 51 5059 99 -0.058 0.068 1000 -1000 -0.034 -1000
ErbB4 signaling events 50 3516 69 -0.068 0.055 1000 -1000 -0.03 -1000
E-cadherin signaling in the nascent adherens junction 50 3870 76 -0.056 0.073 1000 -1000 -0.028 -1000
E-cadherin signaling events 49 248 5 0.035 0.052 1000 -1000 0.037 -1000
Caspase cascade in apoptosis 48 3597 74 -0.097 0.051 1000 -1000 -0.017 -1000
Signaling events mediated by PRL 48 1645 34 -0.017 0.04 1000 -1000 -0.024 -1000
Presenilin action in Notch and Wnt signaling 47 2903 61 -0.16 0.076 1000 -1000 -0.025 -1000
IL2 signaling events mediated by PI3K 47 2731 58 -0.06 0.04 1000 -1000 -0.018 -1000
Class I PI3K signaling events 47 3501 73 -0.016 0.049 1000 -1000 -0.017 -1000
EPO signaling pathway 46 2561 55 -0.001 0.071 1000 -1000 -0.012 -1000
Circadian rhythm pathway 45 992 22 -0.08 0.044 1000 -1000 -0.027 -1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha 45 2046 45 -0.059 0.077 1000 -1000 -0.018 -1000
Stabilization and expansion of the E-cadherin adherens junction 45 3359 74 -0.069 0.065 1000 -1000 -0.052 -1000
Aurora B signaling 45 3051 67 -0.058 0.067 1000 -1000 -0.018 -1000
Arf6 signaling events 44 2734 62 0 0.079 1000 -1000 0 -1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha 44 1455 33 -0.003 0.083 1000 -1000 -0.008 -1000
p75(NTR)-mediated signaling 42 5257 125 -0.069 0.093 1000 -1000 -0.036 -1000
S1P3 pathway 42 1773 42 -0.019 0.053 1000 -1000 -0.003 -1000
PLK1 signaling events 41 3557 85 -0.041 0.051 1000 -1000 -0.019 -1000
Reelin signaling pathway 41 2304 56 -0.016 0.091 1000 -1000 -0.006 -1000
RXR and RAR heterodimerization with other nuclear receptor 41 2157 52 -0.045 0.092 1000 -1000 -0.011 -1000
Regulation of p38-alpha and p38-beta 41 2233 54 -0.032 0.091 1000 -1000 -0.001 -1000
Regulation of Telomerase 41 4239 102 -0.11 0.072 1000 -1000 -0.016 -1000
ErbB2/ErbB3 signaling events 40 2650 65 -0.029 0.047 1000 -1000 -0.04 -1000
Canonical NF-kappaB pathway 40 1570 39 -0.036 0.065 1000 -1000 -0.018 -1000
Regulation of Androgen receptor activity 40 2836 70 -0.087 0.063 1000 -1000 -0.023 -1000
EGFR-dependent Endothelin signaling events 38 799 21 -0.016 0.081 1000 -1000 0 -1000
PDGFR-beta signaling pathway 38 3711 97 -0.039 0.083 1000 -1000 -0.034 -1000
JNK signaling in the CD4+ TCR pathway 37 636 17 -0.004 0.072 1000 -1000 -0.001 -1000
Insulin-mediated glucose transport 37 1203 32 -0.018 0.046 1000 -1000 -0.017 -1000
mTOR signaling pathway 37 1976 53 -0.036 0.059 1000 -1000 -0.015 -1000
FOXA2 and FOXA3 transcription factor networks 36 1667 46 -0.13 0.055 1000 -1000 -0.005 -1000
S1P5 pathway 36 614 17 -0.008 0.04 1000 -1000 -0.021 -1000
Neurotrophic factor-mediated Trk receptor signaling 36 4432 120 -0.054 0.087 1000 -1000 -0.019 -1000
Aurora A signaling 35 2100 60 -0.046 0.064 1000 -1000 -0.017 -1000
p38 MAPK signaling pathway 35 1552 44 -0.035 0.073 1000 -1000 0 -1000
Lissencephaly gene (LIS1) in neuronal migration and development 34 1843 54 -0.017 0.055 1000 -1000 -0.017 -1000
Ceramide signaling pathway 34 2596 76 -0.018 0.079 1000 -1000 -0.017 -1000
ceramide signaling pathway 34 1666 49 -0.034 0.06 1000 -1000 -0.007 -1000
Syndecan-3-mediated signaling events 34 1207 35 -0.011 0.067 1000 -1000 -0.017 -1000
S1P4 pathway 34 855 25 -0.014 0.053 1000 -1000 -0.005 -1000
Arf6 downstream pathway 33 1452 43 -0.036 0.057 1000 -1000 -0.045 -1000
Signaling mediated by p38-gamma and p38-delta 33 495 15 -0.04 0.039 1000 -1000 -0.017 -1000
Regulation of nuclear SMAD2/3 signaling 32 4390 136 -0.093 0.088 1000 -1000 -0.049 -1000
Ephrin A reverse signaling 31 220 7 -0.015 0.039 1000 -1000 -0.008 -1000
Hedgehog signaling events mediated by Gli proteins 31 2054 65 -0.002 0.076 1000 -1000 -0.011 -1000
Class I PI3K signaling events mediated by Akt 31 2134 68 -0.032 0.077 1000 -1000 -0.019 -1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes 31 2629 83 -0.011 0.067 1000 -1000 -0.02 -1000
Signaling events mediated by HDAC Class I 31 3256 104 -0.041 0.076 1000 -1000 -0.039 -1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling 30 710 23 -0.015 0.065 1000 -1000 -0.002 -1000
Atypical NF-kappaB pathway 30 946 31 -0.017 0.04 1000 -1000 -0.017 -1000
Glucocorticoid receptor regulatory network 29 3319 114 -0.1 0.074 1000 -1000 -0.042 -1000
Signaling events regulated by Ret tyrosine kinase 29 2396 82 -0.01 0.093 1000 -1000 -0.022 -1000
Sphingosine 1-phosphate (S1P) pathway 28 804 28 -0.019 0.053 1000 -1000 -0.017 -1000
Insulin Pathway 28 2123 74 -0.026 0.1 1000 -1000 -0.028 -1000
Class IB PI3K non-lipid kinase events 28 84 3 -0.039 0.039 1000 -1000 -0.037 -1000
Coregulation of Androgen receptor activity 27 2076 76 -0.011 0.051 1000 -1000 -0.018 -1000
Nephrin/Neph1 signaling in the kidney podocyte 27 923 34 -0.048 0.084 1000 -1000 -0.047 -1000
Glypican 1 network 27 1342 48 -0.039 0.067 1000 -1000 -0.038 -1000
Signaling events mediated by VEGFR1 and VEGFR2 27 3460 125 -0.02 0.069 1000 -1000 -0.017 -1000
LPA4-mediated signaling events 25 307 12 -0.015 0.045 1000 -1000 -0.013 -1000
IL27-mediated signaling events 25 1310 51 -0.009 0.08 1000 -1000 -0.026 -1000
Alternative NF-kappaB pathway 25 329 13 0 0.093 1000 -1000 0 -1000
Signaling events mediated by HDAC Class II 24 1866 75 -0.036 0.092 1000 -1000 -0.024 -1000
Signaling events mediated by HDAC Class III 24 975 40 -0.062 0.071 1000 -1000 -0.055 -1000
VEGFR1 specific signals 24 1375 56 -0.03 0.045 1000 -1000 -0.02 -1000
Angiopoietin receptor Tie2-mediated signaling 24 2192 88 -0.045 0.075 1000 -1000 -0.047 -1000
Sumoylation by RanBP2 regulates transcriptional repression 23 643 27 -0.031 0.083 1000 -1000 -0.023 -1000
Aurora C signaling 22 160 7 0 0.06 1000 -1000 0 -1000
Signaling mediated by p38-alpha and p38-beta 22 984 44 -0.028 0.052 1000 -1000 -0.009 -1000
Effects of Botulinum toxin 22 573 26 -0.01 0.069 1000 -1000 -0.009 -1000
Calcium signaling in the CD4+ TCR pathway 22 700 31 -0.024 0.082 1000 -1000 -0.028 -1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes 22 1512 68 -0.077 0.094 1000 -1000 -0.03 -1000
Rapid glucocorticoid signaling 22 444 20 -0.01 0.046 1000 -1000 -0.01 -1000
S1P1 pathway 21 784 36 0 0.043 1000 -1000 -0.003 -1000
Arf6 trafficking events 19 1363 71 -0.046 0.05 1000 -1000 -0.038 -1000
Arf1 pathway 19 1071 54 -0.009 0.051 1000 -1000 -0.01 -1000
Signaling events mediated by Stem cell factor receptor (c-Kit) 17 1326 78 -0.017 0.063 1000 -1000 -0.042 -1000
Glypican 2 network 16 64 4 0.039 0.054 1000 -1000 0.037 -1000
Visual signal transduction: Rods 14 736 52 -0.017 0.097 1000 -1000 -0.006 -1000
Visual signal transduction: Cones 13 520 38 -0.01 0.089 1000 -1000 -0.012 -1000
Total 6285 347164 7203 -7.1 8.2 131000 -131000 -2.6 -131000
PLK2 and PLK4 events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PLK2 0.026 0.02 -9999 0 0 207 207
PLK4 0.036 0.014 -9999 0 0 74 74
regulation of centriole replication -0.011 0.01 0 251 -9999 0 251
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 Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
NFATC3 -0.34 0.6 -10000 0 -1.1 159 159
PLK1 -0.045 0.3 -10000 0 -1.2 32 32
BIRC5 -0.053 0.33 -10000 0 -1.3 33 33
HSPA1B -0.34 0.6 -10000 0 -1.1 177 177
MAP2K1 0.003 0.07 -10000 0 -10000 0 0
BRCA2 -0.35 0.61 -10000 0 -1.1 170 170
FOXM1 -0.51 0.88 -10000 0 -1.6 176 176
XRCC1 -0.34 0.6 0.75 1 -1.1 168 169
FOXM1B/p19 -0.43 0.66 -10000 0 -1.3 179 179
Cyclin D1/CDK4 -0.35 0.56 -10000 0 -1 183 183
CDC2 -0.4 0.68 -10000 0 -1.3 181 181
TGFA -0.32 0.52 -10000 0 -0.98 169 169
SKP2 -0.34 0.61 -10000 0 -1.1 167 167
CCNE1 0.018 0.028 -10000 0 -0.033 66 66
CKS1B -0.34 0.61 -10000 0 -1.1 168 168
RB1 -0.31 0.47 -10000 0 -0.94 165 165
FOXM1C/SP1 -0.43 0.71 -10000 0 -1.3 178 178
AURKB -0.11 0.41 -10000 0 -1.2 61 61
CENPF -0.38 0.63 -10000 0 -1.2 182 182
CDK4 0.008 0.044 0.11 1 -0.038 188 189
MYC -0.33 0.48 -10000 0 -0.94 177 177
CHEK2 0.006 0.065 -10000 0 -10000 0 0
ONECUT1 -0.35 0.58 -10000 0 -1.1 170 170
CDKN2A 0.026 0.02 0.089 2 -0.033 7 9
LAMA4 -0.38 0.63 -10000 0 -1.2 186 186
FOXM1B/HNF6 -0.44 0.71 -10000 0 -1.4 170 170
FOS -0.42 0.65 -10000 0 -1.2 214 214
SP1 0.035 0.022 -10000 0 -0.032 48 48
CDC25B -0.34 0.6 -10000 0 -1.1 167 167
response to radiation -0.006 0.036 0.088 6 -10000 0 6
CENPB -0.34 0.6 -10000 0 -1.1 163 163
CENPA -0.35 0.6 -10000 0 -1.1 167 167
NEK2 -0.36 0.61 -10000 0 -1.2 169 169
HIST1H2BA -0.34 0.6 -10000 0 -1.1 164 164
CCNA2 0.023 0.03 -10000 0 -0.013 201 201
EP300 0.036 0.014 -10000 0 0 69 69
CCNB1/CDK1 -0.48 0.78 -10000 0 -1.5 175 175
CCNB2 -0.38 0.62 -10000 0 -1.2 178 178
CCNB1 -0.38 0.66 -10000 0 -1.2 169 169
ETV5 -0.35 0.64 -10000 0 -1.2 185 185
ESR1 -0.38 0.62 -10000 0 -1.1 189 189
CCND1 -0.36 0.56 -10000 0 -1 183 183
GSK3A 0.005 0.061 0.16 1 -10000 0 1
Cyclin A-E1/CDK1-2 -0.009 0.1 -10000 0 -0.16 116 116
CDK2 0.027 0.029 -10000 0 -0.02 138 138
G2/M transition of mitotic cell cycle -0.007 0.043 0.099 5 -10000 0 5
FOXM1B/Cbp/p300 -0.39 0.66 -10000 0 -1.2 174 174
GAS1 -0.35 0.6 -10000 0 -1.1 171 171
MMP2 -0.42 0.65 -10000 0 -1.2 212 212
RB1/FOXM1C -0.4 0.59 0.67 1 -1.1 180 181
CREBBP 0.037 0.012 -10000 0 0 53 53
TCGA08_p53

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CDKN2A -0.007 0.005 0 167 -10000 0 167
TP53 -0.052 0.12 0.18 12 -0.24 143 155
Senescence -0.053 0.12 0.18 12 -0.24 145 157
Apoptosis -0.053 0.12 0.18 12 -0.24 145 157
Activated_Oncogenes 0 0 -10000 0 -10000 0 0
MDM2 -0.004 0.044 0.3 11 -10000 0 11
MDM4 0.038 0.012 -10000 0 0 47 47
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 Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PKM2 0.046 0.34 0.56 50 -0.54 81 131
HDAC7 -0.001 0.004 -10000 0 -0.039 1 1
HIF1A/ARNT/Cbp/p300/Src-1 0.018 0.31 0.57 3 -0.58 57 60
SMAD4 0.038 0.011 -10000 0 0 43 43
ID2 0.046 0.34 0.56 51 -0.54 81 132
AP1 0.006 0.084 -10000 0 -0.14 118 118
ABCG2 0.042 0.34 0.56 49 -0.54 80 129
HIF1A 0.028 0.11 0.2 43 -0.14 78 121
TFF3 0.024 0.32 0.56 40 -0.54 80 120
GATA2 0.04 0.018 -10000 0 -0.056 11 11
AKT1 0.042 0.098 0.22 32 -0.12 61 93
response to hypoxia 0.004 0.07 0.15 36 -0.12 55 91
MCL1 0.034 0.33 0.55 45 -0.55 80 125
NDRG1 0 0.3 0.53 30 -0.56 70 100
SERPINE1 0 0.31 0.55 30 -0.55 78 108
FECH 0.043 0.34 0.56 50 -0.55 78 128
FURIN 0.046 0.34 0.56 52 -0.54 80 132
NCOA2 0.038 0.014 -10000 0 -0.001 61 61
EP300 0.046 0.12 0.29 48 -0.25 22 70
HMOX1 0.032 0.33 0.55 43 -0.55 81 124
BHLHE40 -0.025 0.29 0.46 50 -0.53 82 132
BHLHE41 -0.025 0.29 0.46 50 -0.53 82 132
HIF1A/ARNT/SMAD3/SMAD4/SP1 0.087 0.15 0.35 13 -0.21 35 48
ENG 0.032 0.12 0.28 26 -0.21 24 50
JUN 0.035 0.018 -10000 0 -0.042 10 10
RORA 0.045 0.34 0.56 49 -0.54 80 129
ABCB1 0.014 0.093 -10000 0 -0.55 4 4
TFRC 0.004 0.31 0.55 32 -0.55 79 111
CXCR4 0.019 0.33 0.55 42 -0.55 83 125
TF 0.04 0.33 0.56 50 -0.54 80 130
CITED2 0.042 0.33 0.55 49 -0.54 81 130
HIF1A/ARNT 0.018 0.37 -10000 0 -0.68 56 56
LDHA -0.048 0.29 -10000 0 -0.93 50 50
ETS1 0.024 0.33 0.55 39 -0.57 78 117
PGK1 0.045 0.34 0.56 50 -0.56 81 131
NOS2 -0.025 0.29 0.46 50 -0.53 82 132
ITGB2 0.025 0.34 0.55 41 -0.56 85 126
ALDOA 0.052 0.34 0.56 54 -0.54 81 135
Cbp/p300/CITED2 0.017 0.33 0.55 32 -0.61 67 99
FOS 0.026 0.022 -10000 0 -0.001 206 206
HK2 0.045 0.34 0.56 51 -0.55 79 130
SP1 0.047 0.009 -10000 0 -10000 0 0
GCK 0.067 0.16 0.53 8 -0.41 1 9
HK1 0.049 0.34 0.55 53 -0.54 81 134
NPM1 0.051 0.34 0.56 53 -0.54 82 135
EGLN1 0.049 0.33 0.55 54 -0.54 80 134
CREB1 0.034 0.042 -10000 0 -0.11 40 40
PGM1 0.038 0.34 0.56 46 -0.56 81 127
SMAD3 0.04 0.009 -10000 0 0 23 23
EDN1 0.037 0.21 0.46 5 -1 12 17
IGFBP1 0.051 0.34 0.56 53 -0.54 80 133
VEGFA -0.009 0.26 0.44 34 -0.5 66 100
HIF1A/JAB1 0.035 0.099 0.19 15 -0.14 87 102
CP -0.006 0.31 0.54 36 -0.56 80 116
CXCL12 -0.012 0.31 0.56 27 -0.55 83 110
COPS5 0.036 0.015 -10000 0 -0.001 80 80
SMAD3/SMAD4 0.052 0.032 -10000 0 -0.13 10 10
BNIP3 0.026 0.33 0.56 41 -0.57 77 118
EGLN3 -0.006 0.32 0.55 31 -0.56 88 119
CA9 -0.006 0.31 0.55 28 -0.54 82 110
TERT 0.036 0.33 0.55 46 -0.54 78 124
ENO1 0.048 0.34 0.56 51 -0.55 80 131
PFKL 0.051 0.34 0.56 52 -0.54 81 133
NCOA1 0.04 0.009 -10000 0 -0.001 23 23
ADM 0.011 0.32 0.56 27 -0.55 83 110
ARNT 0.027 0.095 0.19 36 -0.12 69 105
HNF4A 0.041 0.011 -10000 0 -10000 0 0
ADFP 0.01 0.32 0.55 36 -0.55 86 122
SLC2A1 0.013 0.29 0.48 32 -0.52 70 102
LEP 0.049 0.34 0.56 51 -0.55 78 129
HIF1A/ARNT/Cbp/p300 0.01 0.31 0.57 3 -0.6 57 60
EPO 0.039 0.28 0.52 22 -0.53 52 74
CREBBP 0.051 0.12 0.29 51 -0.22 16 67
HIF1A/ARNT/Cbp/p300/HDAC7 0.002 0.3 0.54 3 -0.59 58 61
PFKFB3 0.041 0.34 0.56 49 -0.56 79 128
NT5E -0.027 0.31 0.54 22 -0.56 89 111
Ephrin B reverse signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
EFNB2 0.031 0.018 -10000 0 0 139 139
EPHB2 0.042 0.013 -10000 0 0 38 38
EFNB1 0.001 0.024 0.026 246 -10000 0 246
mol:GTP 0 0 -10000 0 -10000 0 0
Rac1/GDP 0.075 0.066 -10000 0 -0.12 19 19
Ephrin B2/EPHB1-2 0.039 0.068 -10000 0 -0.1 78 78
neuron projection morphogenesis 0.051 0.052 -10000 0 -0.11 24 24
Ephrin B1/EPHB1-2/Tiam1 0.069 0.061 0.2 1 -0.11 29 30
DNM1 0.041 0.011 -10000 0 0 33 33
cell-cell signaling 0.003 0.005 -10000 0 -10000 0 0
MAP2K4 -0.14 0.21 0.23 3 -0.46 159 162
YES1 -0.19 0.33 -10000 0 -0.7 157 157
Ephrin B1/EPHB1-2/NCK2 0.079 0.05 0.19 2 -0.11 15 17
PI3K -0.1 0.22 -10000 0 -0.44 159 159
mol:GDP 0.067 0.059 0.19 1 -0.11 29 30
ITGA2B 0.04 0.008 -10000 0 0 22 22
endothelial cell proliferation 0.024 0.06 -10000 0 -0.11 82 82
FYN -0.2 0.33 -10000 0 -0.7 159 159
MAP3K7 -0.14 0.23 0.22 3 -0.49 155 158
FGR -0.19 0.32 -10000 0 -0.68 161 161
TIAM1 0.036 0.013 -10000 0 0 66 66
PIK3R1 0.034 0.016 -10000 0 0 99 99
RGS3 0.04 0.007 -10000 0 0 15 15
cell adhesion -0.11 0.21 -10000 0 -0.41 159 159
LYN -0.19 0.32 -10000 0 -0.7 155 155
Ephrin B1/EPHB1-2/Src Family Kinases -0.18 0.29 -10000 0 -0.63 160 160
Ephrin B1/EPHB1-2 -0.14 0.24 -10000 0 -0.53 149 149
SRC -0.18 0.32 -10000 0 -0.69 158 158
ITGB3 0.032 0.017 -10000 0 0 116 116
EPHB1 0.04 0.013 -10000 0 0 50 50
EPHB4 0.039 0.008 -10000 0 0 23 23
RAC1 0.039 0.009 -10000 0 0 28 28
Ephrin B2/EPHB4 0.025 0.06 -10000 0 -0.11 82 82
alphaIIb/beta3 Integrin 0.039 0.05 -10000 0 -0.13 35 35
BLK -0.2 0.32 -10000 0 -0.7 158 158
HCK -0.19 0.32 -10000 0 -0.69 155 155
regulation of stress fiber formation -0.076 0.049 0.11 15 -0.19 2 17
MAPK8 -0.13 0.21 0.21 4 -0.44 160 164
Ephrin B1/EPHB1-2/RGS3 0.079 0.05 0.19 2 -0.11 15 17
endothelial cell migration -0.11 0.18 0.19 5 -0.41 145 150
NCK2 0.041 0.004 -10000 0 0 6 6
PTPN13 0.022 0.022 -10000 0 0 271 271
regulation of focal adhesion formation -0.076 0.049 0.11 15 -0.19 2 17
chemotaxis -0.076 0.049 0.11 15 -0.19 2 17
PIK3CA 0.029 0.019 -10000 0 0 166 166
Rac1/GTP 0.064 0.059 -10000 0 -0.11 22 22
angiogenesis -0.14 0.24 -10000 0 -0.53 153 153
LCK -0.19 0.32 -10000 0 -0.68 161 161
LPA receptor mediated events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
GNB1/GNG2 0.019 0.078 -10000 0 -0.13 109 109
NF kappa B1 p50/RelA/I kappa B alpha -0.009 0.11 0.21 4 -0.22 67 71
AP1 -0.026 0.067 -10000 0 -0.12 170 170
mol:PIP3 -0.035 0.056 -10000 0 -0.13 122 122
AKT1 0 0.091 0.24 14 -0.24 13 27
PTK2B -0.043 0.1 0.12 3 -0.18 172 175
RHOA 0.002 0.06 0.18 1 -0.31 9 10
PIK3CB 0.034 0.016 -10000 0 0 95 95
mol:Ca2+ -0.009 0.05 0.19 8 -0.14 22 30
MAGI3 0.039 0.009 -10000 0 0 30 30
RELA 0.04 0.006 -10000 0 0 10 10
apoptosis 0.002 0.068 0.072 119 -0.14 94 213
HRAS/GDP 0.029 0.007 -10000 0 -10000 0 0
positive regulation of microtubule depolymerization -0.042 0.1 0.19 17 -0.2 108 125
NF kappa B1 p50/RelA -0.03 0.075 0.1 2 -0.16 112 114
endothelial cell migration -0.041 0.12 -10000 0 -0.29 100 100
ADCY4 -0.021 0.096 0.14 8 -0.19 107 115
ADCY5 -0.019 0.095 0.15 7 -0.19 106 113
ADCY6 -0.021 0.096 0.15 7 -0.2 106 113
ADCY7 -0.02 0.095 0.15 7 -0.19 102 109
ADCY1 -0.02 0.096 0.15 7 -0.2 106 113
ADCY2 -0.016 0.093 0.13 12 -0.19 100 112
ADCY3 -0.021 0.097 0.14 7 -0.2 108 115
ADCY8 -0.006 0.088 0.12 28 -0.18 89 117
ADCY9 -0.024 0.099 0.14 8 -0.2 110 118
GSK3B -0.041 0.11 0.21 14 -0.18 167 181
arachidonic acid secretion -0.029 0.097 0.14 4 -0.19 124 128
GNG2 0.039 0.009 -10000 0 0 29 29
TRIP6 0.013 0.048 -10000 0 -0.24 15 15
GNAO1 0.007 0.071 0.091 114 -0.14 85 199
HRAS 0.039 0.01 -10000 0 0 31 31
NFKBIA -0.032 0.092 0.18 7 -0.24 56 63
GAB1 0.037 0.013 -10000 0 0 58 58
mol:GTP 0 0 -10000 0 -10000 0 0
lamellipodium assembly -0.008 0.26 -10000 0 -0.88 43 43
JUN 0.036 0.014 -10000 0 0 76 76
LPA/LPA2/NHERF2 0.014 0.037 -10000 0 -0.062 96 96
TIAM1 -0.032 0.29 -10000 0 -1 43 43
PIK3R1 0.034 0.016 -10000 0 0 99 99
mol:IP3 -0.004 0.044 0.19 9 -0.14 14 23
PLCB3 0.014 0.044 0.17 10 -0.062 95 105
FOS 0.026 0.02 -10000 0 0 201 201
positive regulation of mitosis -0.029 0.097 0.14 4 -0.19 124 128
LPA/LPA1-2-3 -0.017 0.05 -10000 0 -0.12 101 101
mol:Ca ++ 0 0 -10000 0 -10000 0 0
JNK cascade 0 0 -10000 0 -10000 0 0
BCAR1 0.036 0.013 -10000 0 0 65 65
stress fiber formation -0.009 0.096 -10000 0 -0.25 38 38
GNAZ 0.006 0.074 0.092 115 -0.14 90 205
EGFR/PI3K-beta/Gab1 -0.024 0.065 -10000 0 -0.13 123 123
positive regulation of dendritic cell cytokine production -0.017 0.049 -10000 0 -0.12 101 101
LPA/LPA2/MAGI-3 0.015 0.037 -10000 0 -0.06 98 98
ARHGEF1 0.005 0.073 0.2 7 -0.13 90 97
GNAI2 0.006 0.076 0.092 121 -0.14 98 219
GNAI3 0.003 0.08 0.092 117 -0.15 99 216
GNAI1 0.003 0.079 0.092 114 -0.16 91 205
LPA/LPA3 -0.01 0.026 -10000 0 -0.064 101 101
LPA/LPA2 -0.01 0.026 -10000 0 -0.064 101 101
LPA/LPA1 -0.025 0.067 -10000 0 -0.17 101 101
HB-EGF/EGFR 0.023 0.052 -10000 0 -0.13 49 49
HBEGF -0.014 0.01 -10000 0 -10000 0 0
mol:DAG -0.004 0.044 0.19 9 -0.14 14 23
cAMP biosynthetic process -0.024 0.098 0.16 9 -0.19 103 112
NFKB1 0.036 0.013 -10000 0 0 66 66
SRC 0.039 0.009 -10000 0 0 28 28
GNB1 0.039 0.01 -10000 0 0 33 33
LYN -0.025 0.095 0.2 10 -0.23 58 68
GNAQ 0.008 0.032 0.044 116 -0.053 102 218
LPAR2 0 0.001 -10000 0 -10000 0 0
LPAR3 0 0 -10000 0 -10000 0 0
LPAR1 -0.017 0.041 -10000 0 -0.1 101 101
IL8 -0.024 0.17 0.26 4 -0.38 83 87
PTK2 0.007 0.063 0.096 84 -0.12 78 162
Rac1/GDP 0.029 0.009 -10000 0 -0.12 1 1
CASP3 0.002 0.068 0.072 117 -0.14 94 211
EGFR 0.036 0.014 -10000 0 0 67 67
PLCG1 0.005 0.036 -10000 0 -0.094 27 27
PLD2 0.015 0.066 0.095 118 -0.12 90 208
G12/G13 0.02 0.077 -10000 0 -0.13 104 104
PI3K-beta -0.023 0.072 -10000 0 -0.21 38 38
cell migration -0.007 0.086 -10000 0 -0.25 43 43
SLC9A3R2 0.037 0.012 -10000 0 0 54 54
PXN -0.01 0.098 -10000 0 -0.25 38 38
HRAS/GTP -0.029 0.099 0.14 4 -0.19 123 127
RAC1 0.039 0.009 -10000 0 0 28 28
MMP9 0.028 0.019 -10000 0 0 169 169
PRKCE 0.039 0.009 -10000 0 0 28 28
PRKCD -0.018 0.057 0.18 10 -0.16 24 34
Gi(beta/gamma) -0.023 0.1 0.16 4 -0.19 123 127
mol:LPA -0.017 0.041 -10000 0 -0.1 101 101
TRIP6/p130 Cas/FAK1/Paxillin -0.003 0.1 0.19 3 -0.2 75 78
MAPKKK cascade -0.029 0.097 0.14 4 -0.19 124 128
contractile ring contraction involved in cytokinesis 0.001 0.062 0.16 2 -0.31 10 12
mol:GDP 0 0 -10000 0 -10000 0 0
GNA14 0.008 0.033 0.044 116 -0.052 109 225
GNA15 0.008 0.031 0.043 108 -0.054 91 199
GNA12 0.039 0.01 -10000 0 0 33 33
GNA13 0.039 0.008 -10000 0 0 23 23
MAPT -0.042 0.1 0.19 17 -0.2 108 125
GNA11 0.008 0.031 0.043 108 -0.054 95 203
Rac1/GTP -0.011 0.27 -10000 0 -0.93 43 43
MMP2 -0.042 0.12 -10000 0 -0.29 100 100
Endothelins

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 -0.01 0.14 0.22 29 -0.24 118 147
PTK2B 0.034 0.016 -10000 0 0 97 97
mol:Ca2+ -0.032 0.2 -10000 0 -0.5 45 45
EDN1 -0.009 0.1 0.22 7 -0.18 126 133
EDN3 0.037 0.013 -10000 0 0 60 60
EDN2 0.037 0.012 -10000 0 0 52 52
HRAS/GDP -0.053 0.19 0.26 2 -0.35 113 115
ETA receptor/Endothelin-1/Gq/GTP/PLC beta -0.031 0.14 0.22 1 -0.27 104 105
ADCY4 0.006 0.13 0.21 63 -0.23 72 135
ADCY5 0.006 0.13 0.21 55 -0.23 72 127
ADCY6 0.006 0.14 0.21 62 -0.23 74 136
ADCY7 0.005 0.14 0.21 55 -0.23 73 128
ADCY1 0.006 0.14 0.21 57 -0.23 73 130
ADCY2 0.005 0.13 0.22 47 -0.23 61 108
ADCY3 0.005 0.14 0.21 65 -0.24 73 138
ADCY8 -0.004 0.1 0.21 28 -0.23 48 76
ADCY9 0.004 0.14 0.21 56 -0.23 76 132
arachidonic acid secretion -0.1 0.26 0.26 1 -0.49 136 137
ETB receptor/Endothelin-1/Gq/GTP -0.004 0.11 -10000 0 -0.24 61 61
GNAO1 0.035 0.015 -10000 0 0 85 85
HRAS 0.039 0.01 -10000 0 0 31 31
ETA receptor/Endothelin-1/G12/GTP -0.011 0.13 0.34 6 -0.21 126 132
ETA receptor/Endothelin-1/Gs/GTP -0.008 0.12 0.32 7 -0.2 122 129
mol:GTP 0 0.006 -10000 0 -0.025 3 3
COL3A1 -0.06 0.16 0.27 7 -0.36 116 123
EDNRB 0.021 0.053 0.091 5 -0.086 95 100
response to oxidative stress 0 0 -10000 0 -10000 0 0
CYSLTR2 -0.01 0.14 0.28 9 -0.25 99 108
CYSLTR1 -0.021 0.14 0.25 8 -0.26 113 121
SLC9A1 -0.018 0.085 0.2 7 -0.16 98 105
mol:GDP -0.067 0.19 0.25 2 -0.36 116 118
SLC9A3 -0.026 0.19 -10000 0 -0.55 31 31
RAF1 -0.077 0.22 0.26 9 -0.4 140 149
JUN -0.073 0.29 -10000 0 -0.81 56 56
JAK2 -0.013 0.14 0.22 28 -0.24 114 142
mol:IP3 -0.026 0.15 0.2 2 -0.31 81 83
ETA receptor/Endothelin-1 -0.037 0.15 0.38 6 -0.27 135 141
PLCB1 0.033 0.016 -10000 0 0 106 106
PLCB2 0.037 0.014 -10000 0 -0.006 45 45
ETA receptor/Endothelin-3 0.015 0.084 0.19 7 -0.12 118 125
FOS -0.14 0.36 0.33 1 -0.82 109 110
Gai/GDP -0.018 0.21 -10000 0 -0.71 44 44
CRK 0.038 0.012 -10000 0 0 49 49
mol:Ca ++ -0.035 0.19 0.25 27 -0.34 116 143
BCAR1 0.036 0.013 -10000 0 0 65 65
PRKCB1 -0.03 0.15 0.22 7 -0.3 84 91
GNAQ 0.034 0.022 -10000 0 -0.039 30 30
GNAZ 0.038 0.011 -10000 0 0 46 46
GNAL 0.04 0.008 -10000 0 0 22 22
Gs family/GDP -0.052 0.18 0.25 2 -0.34 111 113
ETA receptor/Endothelin-1/Gq/GTP -0.022 0.14 0.21 5 -0.28 84 89
MAPK14 -0.023 0.11 0.23 2 -0.25 75 77
TRPC6 -0.035 0.2 -10000 0 -0.52 44 44
GNAI2 0.04 0.006 -10000 0 0 13 13
GNAI3 0.038 0.011 -10000 0 0 45 45
GNAI1 0.034 0.015 -10000 0 0 93 93
ETB receptor/Endothelin-1/Gq/GTP/PLC beta -0.018 0.12 -10000 0 -0.25 79 79
ETB receptor/Endothelin-2 0.031 0.054 -10000 0 -0.07 85 85
ETB receptor/Endothelin-3 0.033 0.051 -10000 0 -0.065 82 82
ETB receptor/Endothelin-1 0 0.1 0.2 5 -0.19 100 105
MAPK3 -0.13 0.34 0.32 3 -0.76 112 115
MAPK1 -0.14 0.35 0.32 3 -0.75 117 120
Rac1/GDP -0.054 0.19 0.26 2 -0.35 111 113
cAMP biosynthetic process 0.034 0.13 0.24 43 -0.23 29 72
MAPK8 -0.052 0.23 -10000 0 -0.54 70 70
SRC 0.039 0.009 -10000 0 0 28 28
ETB receptor/Endothelin-1/Gi/GTP -0.01 0.11 -10000 0 -0.26 58 58
p130Cas/CRK/Src/PYK2 -0.06 0.2 0.36 1 -0.4 91 92
mol:K + 0 0 -10000 0 -10000 0 0
G12/GDP -0.054 0.19 0.27 1 -0.35 112 113
COL1A2 -0.079 0.22 0.28 6 -0.49 106 112
EntrezGene:2778 0 0 -10000 0 -10000 0 0
ETA receptor/Endothelin-2 0.012 0.088 0.18 8 -0.13 125 133
mol:DAG -0.026 0.15 0.2 2 -0.31 81 83
MAP2K2 -0.1 0.27 0.29 4 -0.55 124 128
MAP2K1 -0.11 0.28 0.29 4 -0.56 125 129
EDNRA -0.004 0.1 0.22 8 -0.17 134 142
positive regulation of muscle contraction -0.016 0.12 0.21 24 -0.24 81 105
Gq family/GDP -0.019 0.19 -10000 0 -0.32 110 110
HRAS/GTP -0.055 0.18 0.24 3 -0.33 122 125
PRKCH -0.034 0.15 0.2 1 -0.3 91 92
RAC1 0.039 0.009 -10000 0 0 28 28
PRKCA -0.031 0.15 0.23 4 -0.31 85 89
PRKCB -0.03 0.15 0.19 2 -0.29 93 95
PRKCE -0.032 0.15 0.28 5 -0.3 89 94
PRKCD -0.033 0.15 0.24 2 -0.3 87 89
PRKCG -0.033 0.15 0.23 6 -0.3 89 95
regulation of vascular smooth muscle contraction -0.18 0.44 -10000 0 -1 106 106
PRKCQ -0.034 0.15 0.26 5 -0.31 88 93
PLA2G4A -0.12 0.28 -10000 0 -0.53 136 136
GNA14 0.035 0.021 -10000 0 -0.038 33 33
GNA15 0.033 0.022 -10000 0 -0.035 29 29
GNA12 0.039 0.01 -10000 0 0 33 33
GNA11 0.033 0.021 -10000 0 -0.012 91 91
Rac1/GTP -0.011 0.13 0.34 6 -0.21 125 131
MMP1 0.023 0.12 0.3 21 -0.58 9 30
Syndecan-1-mediated signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
TGFB1 0.036 0.014 -10000 0 0 69 69
CCL5 0.029 0.019 -10000 0 0 160 160
SDCBP 0.035 0.014 -10000 0 0 77 77
FGFR/FGF2/Syndecan-1 -0.018 0.12 0.2 14 -0.32 44 58
mol:PI-4-5-P2 0 0 -10000 0 -10000 0 0
RP11-540L11.1 0 0 -10000 0 -10000 0 0
Syndecan-1/Laminin-5 -0.017 0.14 0.23 15 -0.3 59 74
Syndecan-1/Syntenin -0.017 0.14 0.23 21 -0.29 67 88
MAPK3 -0.025 0.13 0.2 22 -0.28 64 86
HGF/MET 0.013 0.074 -10000 0 -0.13 102 102
TGFB1/TGF beta receptor Type II 0.036 0.014 -10000 0 0 69 69
BSG 0.036 0.014 -10000 0 0 74 74
keratinocyte migration -0.016 0.14 0.23 15 -0.3 59 74
Syndecan-1/RANTES -0.021 0.15 0.22 21 -0.29 79 100
Syndecan-1/CD147 -0.004 0.15 0.26 17 -0.29 63 80
Syndecan-1/Syntenin/PIP2 -0.019 0.14 0.21 19 -0.28 67 86
LAMA5 0.036 0.014 -10000 0 0 72 72
positive regulation of cell-cell adhesion -0.019 0.13 0.21 16 -0.28 67 83
MMP7 0.016 0.02 -10000 0 0 333 333
HGF 0.039 0.009 -10000 0 0 27 27
Syndecan-1/CASK -0.044 0.12 0.15 3 -0.29 65 68
Syndecan-1/HGF/MET -0.021 0.15 0.26 14 -0.27 85 99
regulation of cell adhesion -0.033 0.12 0.19 19 -0.28 59 78
HPSE 0.035 0.014 -10000 0 0 79 79
positive regulation of cell migration -0.018 0.12 0.2 14 -0.32 44 58
SDC1 -0.022 0.12 0.17 4 -0.34 38 42
Syndecan-1/Collagen -0.018 0.12 0.2 14 -0.32 44 58
PPIB 0.04 0.007 -10000 0 0 18 18
MET 0.027 0.02 -10000 0 0 191 191
PRKACA 0.035 0.015 -10000 0 0 84 84
MMP9 0.028 0.019 -10000 0 0 169 169
MAPK1 -0.023 0.13 0.2 22 -0.28 62 84
homophilic cell adhesion -0.018 0.13 0.2 22 -0.31 50 72
MMP1 0.03 0.018 -10000 0 0 151 151
Osteopontin-mediated events

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
IKK alpha homodimer -0.013 0.13 0.21 7 -0.22 114 121
NF kappa B1 p50/RelA/I kappa B alpha -0.043 0.18 0.28 1 -0.35 117 118
alphaV/beta3 Integrin/Osteopontin/Src -0.007 0.11 -10000 0 -0.18 133 133
AP1 -0.047 0.18 0.27 2 -0.28 150 152
ILK -0.029 0.11 0.2 9 -0.23 72 81
bone resorption -0.042 0.1 0.2 2 -0.25 54 56
PTK2B 0.034 0.016 -10000 0 0 97 97
PYK2/p130Cas 0.006 0.12 -10000 0 -0.2 81 81
ITGAV 0.025 0.033 -10000 0 -0.049 64 64
mol:GTP 0 0 -10000 0 -10000 0 0
CD44/Rho Family GTPase/ROCK2 0.028 0.067 -10000 0 -0.14 68 68
alphaV/beta3 Integrin/Osteopontin -0.005 0.12 -10000 0 -0.17 157 157
MAP3K1 -0.028 0.11 0.2 8 -0.24 70 78
JUN 0.036 0.015 -10000 0 0 76 76
MAPK3 -0.05 0.14 0.19 12 -0.28 113 125
MAPK1 -0.047 0.14 0.19 12 -0.28 109 121
Rac1/GDP 0.029 0.009 -10000 0 -0.12 1 1
NFKB1 0.036 0.013 -10000 0 0 66 66
MAPK8 -0.034 0.1 0.19 9 -0.24 73 82
ITGB3 0.023 0.034 -10000 0 -0.049 76 76
NFKBIA -0.065 0.17 0.19 9 -0.35 114 123
FOS 0.026 0.02 -10000 0 0 201 201
CD44 0.034 0.015 -10000 0 0 90 90
CHUK 0.038 0.011 -10000 0 0 46 46
PLAU -0.19 0.42 -10000 0 -1 104 104
NF kappa B1 p50/RelA -0.03 0.2 0.29 1 -0.39 109 110
BCAR1 0.036 0.013 -10000 0 0 65 65
RELA 0.04 0.006 -10000 0 0 10 10
alphaV beta3 Integrin 0.004 0.091 -10000 0 -0.14 130 130
mol:GDP 0 0 -10000 0 -10000 0 0
SYK -0.03 0.1 0.19 12 -0.23 75 87
VAV3 -0.042 0.1 0.17 9 -0.23 88 97
MAP3K14 -0.027 0.12 0.2 10 -0.23 109 119
ROCK2 0.037 0.013 -10000 0 0 58 58
SPP1 0.025 0.032 -10000 0 -0.051 51 51
RAC1 0.039 0.009 -10000 0 0 28 28
Rac1/GTP -0.037 0.11 0.18 10 -0.22 86 96
MMP2 -0.089 0.14 0.22 2 -0.32 124 126
Wnt signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
Noncanonical Wnts/FZD -0.017 0.093 -9999 0 -0.28 38 38
FZD6 0.029 0.019 -9999 0 0 162 162
WNT6 0.04 0.006 -9999 0 0 13 13
WNT4 0.04 0.008 -9999 0 0 19 19
FZD3 0.03 0.019 -9999 0 0 153 153
WNT5A 0.034 0.015 -9999 0 0 89 89
WNT11 0.032 0.017 -9999 0 0 118 118
Nectin adhesion pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PDGFRB 0.036 0.013 -10000 0 0 65 65
alphaV beta3 Integrin 0.014 0.078 -10000 0 -0.15 93 93
PTK2 -0.047 0.14 -10000 0 -0.31 100 100
positive regulation of JNK cascade -0.038 0.15 -10000 0 -0.28 106 106
CDC42/GDP -0.048 0.2 -10000 0 -0.36 131 131
Rac1/GDP -0.05 0.2 -10000 0 -0.36 126 126
RAP1B 0.037 0.012 -10000 0 0 54 54
RAP1A 0.039 0.01 -10000 0 0 35 35
CTNNB1 0.039 0.01 -10000 0 0 32 32
CDC42/GTP -0.044 0.18 -10000 0 -0.34 105 105
nectin-3/I-afadin 0.011 0.073 -10000 0 -0.14 93 93
RAPGEF1 -0.065 0.18 -10000 0 -0.37 126 126
mol:GTP 0 0 -10000 0 -10000 0 0
CRK -0.073 0.2 -10000 0 -0.41 129 129
PDGFB-D/PDGFRB 0.036 0.013 -10000 0 0 65 65
TLN1 -0.036 0.08 0.19 1 -0.24 55 56
Rap1/GTP -0.048 0.14 -10000 0 -0.29 124 124
IQGAP1 0.036 0.013 -10000 0 0 66 66
Rap1/GTP/I-afadin 0.043 0.063 -10000 0 -0.11 61 61
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin 0.011 0.073 -10000 0 -0.14 93 93
PVR 0.038 0.011 -10000 0 0 39 39
Necl-5(dimer) 0.038 0.011 -10000 0 0 39 39
mol:GDP -0.078 0.22 -10000 0 -0.43 131 131
MLLT4 0.033 0.016 -10000 0 0 109 109
PIK3CA 0.029 0.019 -10000 0 0 166 166
PI3K 0.022 0.086 -10000 0 -0.12 90 90
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin 0.042 0.043 -10000 0 -0.13 22 22
positive regulation of lamellipodium assembly -0.047 0.16 -10000 0 -0.3 115 115
PVRL1 0.04 0.008 -10000 0 0 22 22
PVRL3 0.029 0.019 -10000 0 0 158 158
PVRL2 0.037 0.012 -10000 0 0 51 51
PIK3R1 0.034 0.016 -10000 0 0 99 99
CDH1 0.035 0.014 -10000 0 0 79 79
CLDN1 0.022 0.021 -10000 0 0 249 249
JAM-A/CLDN1 0.011 0.087 -10000 0 -0.12 124 124
SRC -0.088 0.21 -10000 0 -0.44 130 130
ITGB3 0.032 0.017 -10000 0 0 116 116
nectin-1(dimer)/I-afadin/I-afadin 0.042 0.043 -10000 0 -0.13 22 22
FARP2 -0.07 0.22 -10000 0 -0.46 90 90
RAC1 0.039 0.009 -10000 0 0 28 28
CTNNA1 0.039 0.01 -10000 0 0 31 31
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer) 0.024 0.075 -10000 0 -0.12 92 92
nectin-1/I-afadin 0.042 0.043 -10000 0 -0.13 22 22
nectin-2/I-afadin 0.038 0.047 -10000 0 -0.14 27 27
RAC1/GTP/IQGAP1/filamentous actin 0.039 0.045 -10000 0 -0.11 40 40
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin 0.026 0.074 -10000 0 -0.12 89 89
CDC42/GTP/IQGAP1/filamentous actin 0.039 0.046 -10000 0 -0.11 42 42
F11R 0.039 0.008 -10000 0 0 24 24
positive regulation of filopodium formation -0.038 0.15 -10000 0 -0.28 106 106
alphaV/beta3 Integrin/Talin -0.033 0.11 0.26 1 -0.22 95 96
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin 0.038 0.047 -10000 0 -0.14 27 27
nectin-2(dimer)/I-afadin/I-afadin 0.038 0.047 -10000 0 -0.14 27 27
PIP5K1C -0.03 0.083 -10000 0 -0.17 109 109
VAV2 -0.088 0.24 -10000 0 -0.48 109 109
RAP1/GDP -0.046 0.19 -10000 0 -0.34 128 128
ITGAV 0.033 0.017 -10000 0 0 110 110
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin 0.022 0.075 -10000 0 -0.12 94 94
nectin-3(dimer)/I-afadin/I-afadin 0.011 0.073 -10000 0 -0.14 93 93
Rac1/GTP -0.057 0.19 -10000 0 -0.37 114 114
PTPRM -0.027 0.094 -10000 0 -0.18 117 117
E-cadherin/beta catenin/alpha catenin 0.063 0.085 -10000 0 -0.13 50 50
adherens junction assembly 0 0 -10000 0 -10000 0 0
CDC42 0.04 0.007 -10000 0 0 18 18
amb2 Integrin signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2 0.006 0.084 -10000 0 -0.12 127 127
alphaM/beta2 Integrin/GPIbA 0.051 0.067 -10000 0 -0.11 57 57
alphaM/beta2 Integrin/proMMP-9 0.029 0.081 -10000 0 -0.13 83 83
PLAUR 0.035 0.015 -10000 0 0 82 82
HMGB1 0.041 0.015 -10000 0 -0.053 9 9
alphaM/beta2 Integrin/Talin 0.047 0.075 -10000 0 -0.12 75 75
AGER 0.041 0.015 -10000 0 -0.053 9 9
RAP1A 0.039 0.01 -10000 0 0 35 35
SELPLG 0.039 0.009 -10000 0 0 25 25
mol:LDL 0 0 -10000 0 -10000 0 0
alphaM/beta2 Integrin/RAGE/HMGB1 0.081 0.08 -10000 0 -0.17 11 11
mol:GTP 0 0 -10000 0 -10000 0 0
MMP9 0.028 0.019 -10000 0 0 169 169
CYR61 0.03 0.018 -10000 0 0 149 149
TLN1 0.038 0.011 -10000 0 0 39 39
Rap1/GTP -0.063 0.17 -10000 0 -0.31 134 134
RHOA 0.04 0.006 -10000 0 0 13 13
P-selectin oligomer 0.039 0.01 -10000 0 0 34 34
MYH2 -0.08 0.17 0.2 2 -0.33 133 135
MST1R 0.038 0.011 -10000 0 0 39 39
leukocyte activation during inflammatory response 0.055 0.063 -10000 0 -0.099 47 47
APOB 0.04 0.007 -10000 0 0 14 14
mol:GDP 0 0 -10000 0 -10000 0 0
complement component iC3b receptor activity 0 0 -10000 0 -10000 0 0
MMP2 0.021 0.021 -10000 0 0 265 265
JAM3 0.038 0.012 -10000 0 0 47 47
GP1BA 0.038 0.011 -10000 0 0 42 42
alphaM/beta2 Integrin/CTGF 0.035 0.079 -10000 0 -0.12 93 93
alphaM/beta2 Integrin -0.066 0.17 -10000 0 -0.35 116 116
JAM3 homodimer 0.038 0.012 -10000 0 0 47 47
ICAM2 0.038 0.01 -10000 0 0 36 36
ICAM1 0.026 0.02 -10000 0 0 206 206
phagocytosis triggered by activation of immune response cell surface activating receptor -0.065 0.17 -10000 0 -0.34 118 118
cell adhesion 0.051 0.067 -10000 0 -0.11 57 57
NFKB1 0.021 0.069 0.3 1 -0.22 20 21
THY1 0.025 0.02 -10000 0 0 216 216
RhoA/GDP 0.029 0.014 -10000 0 -0.12 4 4
Lipoprotein(a) 0.047 0.02 -10000 0 -10000 0 0
alphaM/beta2 Integrin/LRP/tPA 0.024 0.099 -10000 0 -0.13 134 134
IL6 -0.019 0.072 0.3 1 -0.4 10 11
ITGB2 0.034 0.021 -10000 0 -0.051 8 8
elevation of cytosolic calcium ion concentration 0.029 0.1 -10000 0 -0.16 98 98
alphaM/beta2 Integrin/JAM2/JAM3 0.067 0.073 -10000 0 -0.11 52 52
JAM2 0.037 0.012 -10000 0 0 52 52
alphaM/beta2 Integrin/ICAM1 0.05 0.099 -10000 0 -0.14 84 84
alphaM/beta2 Integrin/uPA/Plg 0.038 0.096 -10000 0 -0.14 100 100
RhoA/GTP -0.085 0.18 -10000 0 -0.34 140 140
positive regulation of phagocytosis -0.046 0.15 0.2 2 -0.3 103 105
Ron/MSP 0.054 0.028 -10000 0 -0.13 8 8
alphaM/beta2 Integrin/uPAR/uPA 0.032 0.1 -10000 0 -0.16 98 98
alphaM/beta2 Integrin/uPAR 0.043 0.079 -10000 0 -0.14 63 63
PLAU 0.025 0.02 -10000 0 0 210 210
PLAT 0.026 0.02 -10000 0 0 205 205
actin filament polymerization -0.076 0.16 0.19 2 -0.32 133 135
MST1 0.04 0.007 -10000 0 0 15 15
alphaM/beta2 Integrin/lipoprotein(a) 0.061 0.067 -10000 0 -0.1 47 47
TNF -0.01 0.07 0.29 1 -0.34 7 8
RAP1B 0.037 0.012 -10000 0 0 54 54
alphaM/beta2 Integrin/uPA 0.017 0.092 -10000 0 -0.15 102 102
fibrinolysis 0.036 0.094 -10000 0 -0.14 100 100
HCK 0.036 0.013 -10000 0 0 65 65
dendritic cell antigen processing and presentation -0.065 0.17 -10000 0 -0.34 118 118
VTN 0.039 0.008 -10000 0 0 24 24
alphaM/beta2 Integrin/CYR61 0.024 0.083 -10000 0 -0.12 112 112
LPA 0.035 0.014 -10000 0 0 77 77
LRP1 0.036 0.014 -10000 0 0 69 69
cell migration 0.015 0.092 0.18 10 -0.13 129 139
FN1 0.021 0.021 -10000 0 0 268 268
alphaM/beta2 Integrin/Thy1 0.008 0.091 -10000 0 -0.12 150 150
MPO 0.04 0.007 -10000 0 0 14 14
KNG1 0.034 0.016 -10000 0 0 100 100
RAP1/GDP 0.038 0.05 -10000 0 -0.12 43 43
ROCK1 -0.082 0.17 0.22 3 -0.33 136 139
ELA2 0.036 0.013 -10000 0 0 66 66
PLG 0.038 0.011 -10000 0 0 41 41
CTGF 0.034 0.016 -10000 0 0 101 101
alphaM/beta2 Integrin/Hck 0.05 0.071 -10000 0 -0.13 52 52
ITGAM 0.041 0.015 -10000 0 -0.053 9 9
alphaM/beta2 Integrin/P-Selectin/PSGL1 0.071 0.074 -10000 0 -0.12 51 51
HP 0.01 0.018 -10000 0 0 416 416
leukocyte adhesion 0.017 0.1 -10000 0 -0.18 49 49
SELP 0.039 0.01 -10000 0 0 34 34
PDGFR-alpha signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PDGFRA 0.017 0.035 -10000 0 -0.054 75 75
PDGF/PDGFRA/CRKL 0.013 0.069 -10000 0 -0.13 78 78
positive regulation of JUN kinase activity 0.047 0.081 -10000 0 -0.12 92 92
CRKL 0.038 0.01 -10000 0 0 36 36
PDGF/PDGFRA/Caveolin-3 0.011 0.072 -10000 0 -0.13 88 88
AP1 -0.13 0.25 -10000 0 -0.65 96 96
mol:IP3 -0.018 0.042 0.051 26 -0.098 78 104
PLCG1 -0.018 0.042 0.049 25 -0.098 78 103
PDGF/PDGFRA/alphaV Integrin -0.008 0.09 -10000 0 -0.16 125 125
RAPGEF1 0.039 0.009 -10000 0 0 26 26
CRK 0.038 0.012 -10000 0 0 49 49
mol:Ca2+ -0.018 0.042 0.051 26 -0.098 78 104
CAV3 0.04 0.008 -10000 0 0 19 19
CAV1 0.036 0.014 -10000 0 0 75 75
SHC/Grb2/SOS1 0.049 0.083 -10000 0 -0.12 92 92
PDGF/PDGFRA/Shf 0.012 0.07 -10000 0 -0.13 81 81
FOS -0.12 0.25 0.29 4 -0.64 96 100
JUN -0.031 0.037 0.18 3 -0.2 3 6
oligodendrocyte development -0.008 0.09 -10000 0 -0.16 125 125
GRB2 0.04 0.008 -10000 0 0 21 21
PIK3R1 0.034 0.016 -10000 0 0 99 99
mol:DAG -0.018 0.042 0.051 26 -0.098 78 104
PDGF/PDGFRA 0.017 0.035 -10000 0 -0.054 75 75
actin cytoskeleton reorganization 0.013 0.071 -10000 0 -0.13 85 85
SRF -0.007 0.023 0.032 124 -10000 0 124
SHC1 0.039 0.008 -10000 0 0 23 23
PI3K 0.009 0.079 -10000 0 -0.14 92 92
PDGF/PDGFRA/Crk/C3G 0.033 0.071 -10000 0 -0.11 85 85
JAK1 -0.011 0.02 0.027 36 -10000 0 36
ELK1/SRF -0.025 0.066 0.15 24 -0.15 62 86
SHB 0.04 0.006 -10000 0 0 11 11
SHF 0.039 0.01 -10000 0 0 32 32
CSNK2A1 0.036 0.03 0.084 1 -0.028 59 60
GO:0007205 -0.02 0.053 0.075 7 -0.11 87 94
SOS1 0.037 0.012 -10000 0 0 51 51
Ras protein signal transduction 0.047 0.081 -10000 0 -0.12 92 92
PDGF/PDGFRA/SHB 0.013 0.072 -10000 0 -0.13 85 85
PDGF/PDGFRA/Caveolin-1 0.01 0.074 -10000 0 -0.11 120 120
ITGAV 0.033 0.017 -10000 0 0 110 110
ELK1 -0.031 0.073 0.15 9 -0.18 69 78
PIK3CA 0.029 0.019 -10000 0 0 166 166
PDGF/PDGFRA/Crk 0.012 0.07 -10000 0 -0.1 121 121
JAK-STAT cascade -0.011 0.02 0.027 36 -10000 0 36
cell proliferation 0.012 0.07 -10000 0 -0.13 81 81
TCGA08_retinoblastoma

Figure S14.  Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S14.  Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CDKN2B 0.029 0.026 -10000 0 -0.045 39 39
CDKN2C 0.03 0.027 -10000 0 -0.043 46 46
CDKN2A 0.021 0.029 -10000 0 -0.038 60 60
CCND2 0.009 0.045 0.11 79 -0.12 3 82
RB1 -0.012 0.061 0.18 7 -0.14 83 90
CDK4 0.011 0.055 0.13 80 -0.12 17 97
CDK6 0.005 0.064 0.13 81 -0.14 20 101
G1/S progression 0.019 0.068 0.14 103 -0.19 8 111
Thromboxane A2 receptor signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
TGM2 0.033 0.016 -10000 0 0 105 105
GNB1/GNG2 -0.063 0.086 -10000 0 -0.18 185 185
AKT1 -0.026 0.14 0.25 3 -0.23 82 85
EGF 0.038 0.01 -10000 0 0 38 38
mol:TXA2 0 0.001 -10000 0 -10000 0 0
FGR 0.003 0.058 0.19 12 -0.16 3 15
mol:Ca2+ -0.054 0.19 0.31 2 -0.29 192 194
LYN -0.001 0.055 0.19 11 -0.16 6 17
RhoA/GTP -0.021 0.087 0.14 7 -0.13 178 185
mol:PGI2 0 0 -10000 0 -10000 0 0
SYK -0.074 0.2 0.3 2 -0.34 188 190
GNG2 0.039 0.009 -10000 0 0 29 29
ARRB2 0.038 0.011 -10000 0 0 46 46
TP alpha/Gq family/GDP/G beta5/gamma2 -0.027 0.16 -10000 0 -0.51 50 50
G beta5/gamma2 -0.073 0.12 -10000 0 -0.24 185 185
PRKCH -0.074 0.22 0.31 2 -0.35 186 188
DNM1 0.039 0.01 -10000 0 0 33 33
TXA2/TP beta/beta Arrestin3 0.029 0.022 -10000 0 -10000 0 0
mol:GTP 0 0.002 -10000 0 -10000 0 0
PTGDR 0.041 0.005 -10000 0 0 8 8
G12 family/GTP -0.068 0.18 -10000 0 -0.3 187 187
ADRBK1 0.041 0.004 -10000 0 0 6 6
ADRBK2 0.035 0.015 -10000 0 0 84 84
RhoA/GTP/ROCK1 0.05 0.024 -10000 0 -0.11 9 9
mol:GDP 0.035 0.16 0.45 47 -0.25 2 49
mol:NADP 0.038 0.01 -10000 0 0 35 35
RAB11A 0.04 0.008 -10000 0 0 19 19
PRKG1 0.039 0.009 -10000 0 0 30 30
mol:IP3 -0.077 0.23 0.33 2 -0.37 192 194
cell morphogenesis 0.05 0.023 -10000 0 -0.11 9 9
PLCB2 -0.12 0.3 -10000 0 -0.5 191 191
mol:cGMP 0 0.001 -10000 0 -10000 0 0
BLK 0.002 0.053 0.19 12 -0.17 2 14
mol:PDG2 0 0 -10000 0 -10000 0 0
HCK 0 0.056 0.18 12 -0.16 5 17
RHOA 0.04 0.006 -10000 0 0 13 13
PTGIR 0.039 0.009 -10000 0 0 26 26
PRKCB1 -0.08 0.23 0.33 1 -0.38 187 188
GNAQ 0.038 0.012 -10000 0 0 48 48
mol:L-citrulline 0.038 0.01 -10000 0 0 35 35
TXA2/TXA2-R family -0.12 0.3 0.37 1 -0.52 187 188
LCK 0.003 0.058 0.19 12 -0.16 3 15
TXA2/TP beta/beta Arrestin3/RAB11/GDP 0.051 0.047 0.19 4 -0.15 7 11
TXA2-R family/G12 family/GDP/G beta/gamma 0.001 0.13 -10000 0 -0.41 46 46
TXA2/TP beta/beta Arrestin2/RAB11/GDP 0.047 0.047 0.19 4 -0.15 7 11
MAPK14 -0.044 0.14 0.28 4 -0.23 184 188
TGM2/GTP -0.09 0.25 0.39 1 -0.4 184 185
MAPK11 -0.049 0.14 0.24 3 -0.22 185 188
ARHGEF1 -0.031 0.12 0.19 7 -0.18 180 187
GNAI2 0.04 0.006 -10000 0 0 13 13
JNK cascade -0.08 0.23 0.33 2 -0.38 187 189
RAB11/GDP 0.04 0.008 -10000 0 0 19 19
ICAM1 -0.06 0.2 0.27 8 -0.32 179 187
cAMP biosynthetic process -0.073 0.21 0.31 2 -0.34 191 193
Gq family/GTP/EBP50 0.01 0.049 0.25 2 -0.14 43 45
actin cytoskeleton reorganization 0.05 0.023 -10000 0 -0.11 9 9
SRC 0.001 0.056 0.18 12 -0.16 3 15
GNB5 0.039 0.008 -10000 0 0 23 23
GNB1 0.039 0.01 -10000 0 0 33 33
EGF/EGFR 0.001 0.076 0.22 11 -0.18 22 33
VCAM1 -0.064 0.21 0.27 7 -0.33 186 193
TP beta/Gq family/GDP/G beta5/gamma2 -0.027 0.16 -10000 0 -0.51 50 50
platelet activation -0.059 0.19 0.37 2 -0.3 187 189
PGI2/IP 0.028 0.014 -10000 0 -0.12 4 4
PRKACA 0.019 0.022 -10000 0 -0.16 6 6
Gq family/GDP/G beta5/gamma2 -0.018 0.13 -10000 0 -0.41 46 46
TXA2/TP beta/beta Arrestin2 0.012 0.061 -10000 0 -0.31 13 13
positive regulation of NF-kappaB transcription factor activity 0 0 -10000 0 -10000 0 0
TBXA2R 0.002 0.021 -10000 0 -0.15 6 6
mol:DAG -0.091 0.26 0.36 1 -0.42 187 188
EGFR 0.036 0.014 -10000 0 0 67 67
TXA2/TP alpha -0.11 0.28 0.38 1 -0.46 190 191
Gq family/GTP -0.011 0.066 -10000 0 -0.18 67 67
YES1 0.001 0.056 0.19 12 -0.16 4 16
GNAI2/GTP 0.025 0.046 -10000 0 -0.11 22 22
PGD2/DP 0.03 0.004 -10000 0 -10000 0 0
SLC9A3R1 0.038 0.012 -10000 0 0 49 49
FYN 0 0.055 0.19 12 -0.16 8 20
mol:NO 0.038 0.01 -10000 0 0 35 35
GNA15 0.036 0.014 -10000 0 0 68 68
PGK/cGMP 0.049 0.018 -10000 0 -10000 0 0
RhoA/GDP 0.04 0.007 -10000 0 0 13 13
TP alpha/TGM2/GDP/G beta/gamma 0.057 0.06 0.26 1 -0.18 7 8
NOS3 0.039 0.01 -10000 0 0 35 35
RAC1 0.039 0.009 -10000 0 0 28 28
PRKCA -0.075 0.22 0.32 3 -0.35 186 189
PRKCB -0.072 0.22 0.29 2 -0.35 186 188
PRKCE -0.075 0.22 0.32 4 -0.36 183 187
PRKCD -0.082 0.23 0.33 1 -0.38 184 185
PRKCG -0.081 0.23 0.33 2 -0.38 183 185
muscle contraction -0.11 0.28 0.37 1 -0.48 187 188
PRKCZ -0.071 0.21 0.3 2 -0.34 184 186
ARR3 0.041 0.002 -10000 0 0 1 1
TXA2/TP beta 0.045 0.051 0.23 2 -0.13 10 12
PRKCQ -0.075 0.22 0.34 2 -0.36 180 182
MAPKKK cascade -0.1 0.26 0.35 1 -0.44 188 189
SELE -0.053 0.18 0.27 4 -0.29 187 191
TP beta/GNAI2/GDP/G beta/gamma 0.069 0.057 0.25 2 -0.16 8 10
ROCK1 0.04 0.008 -10000 0 0 21 21
GNA14 0.039 0.009 -10000 0 0 29 29
chemotaxis -0.15 0.34 -10000 0 -0.6 187 187
GNA12 0.039 0.01 -10000 0 0 33 33
GNA13 0.039 0.008 -10000 0 0 23 23
GNA11 0.037 0.013 -10000 0 0 61 61
Rac1/GTP 0.028 0.009 -10000 0 -0.12 1 1
TRAIL signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
TNFSF10 0.021 0.021 -10000 0 0 265 265
positive regulation of NF-kappaB transcription factor activity 0.005 0.065 -10000 0 -0.13 89 89
MAP2K4 -0.008 0.088 0.18 3 -0.27 31 34
IKBKB 0.038 0.011 -10000 0 0 41 41
TNFRSF10B 0.033 0.017 -10000 0 0 111 111
TNFRSF10A 0.032 0.017 -10000 0 0 125 125
SMPD1 -0.007 0.043 -10000 0 -0.1 88 88
IKBKG 0.041 0.002 -10000 0 0 2 2
mol:GTP 0 0 -10000 0 -10000 0 0
TNFRSF10D 0.032 0.017 -10000 0 0 122 122
TRAIL/TRAILR2 0.005 0.066 -10000 0 -0.13 91 91
TRAIL/TRAILR3 0.004 0.066 -10000 0 -0.13 93 93
TRAIL/TRAILR1 0.003 0.067 -10000 0 -0.13 93 93
TRAIL/TRAILR4 0.005 0.065 -10000 0 -0.13 89 89
TRAIL/TRAILR1/DAP3/GTP 0.013 0.064 -10000 0 -0.1 92 92
IKK complex 0.022 0.088 -10000 0 -0.28 29 29
RIPK1 0.039 0.01 -10000 0 0 32 32
response to oxidative stress 0 0 -10000 0 -10000 0 0
DAP3/GTP 0.026 0.021 -10000 0 -0.12 9 9
MAPK3 -0.01 0.01 -10000 0 -10000 0 0
MAP3K1 -0.005 0.096 -10000 0 -0.29 33 33
TRAILR4 (trimer) 0.032 0.017 -10000 0 0 122 122
TRADD 0.037 0.013 -10000 0 0 61 61
TRAILR1 (trimer) 0.032 0.017 -10000 0 0 125 125
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2 -0.017 0.08 -10000 0 -0.17 88 88
CFLAR 0.04 0.008 -10000 0 0 19 19
MAPK1 -0.01 0.01 -10000 0 -10000 0 0
TRAIL/TRAILR1/FADD/TRADD/RIP 0.032 0.082 -10000 0 -0.11 79 79
mol:ceramide -0.007 0.043 -10000 0 -0.099 88 88
FADD 0.04 0.008 -10000 0 0 20 20
MAPK8 -0.02 0.097 0.2 3 -0.26 47 50
TRAF2 0.039 0.01 -10000 0 0 32 32
TRAILR3 (trimer) 0.032 0.017 -10000 0 0 119 119
CHUK 0.038 0.011 -10000 0 0 46 46
TRAIL/TRAILR1/FADD 0.014 0.069 -10000 0 -0.11 89 89
DAP3 0.038 0.011 -10000 0 0 40 40
CASP10 -0.006 0.1 0.16 81 -0.2 76 157
JNK cascade 0.005 0.065 -10000 0 -0.13 89 89
TRAIL (trimer) 0.021 0.021 -10000 0 0 265 265
TNFRSF10C 0.032 0.017 -10000 0 0 119 119
TRAIL/TRAILR1/DAP3/GTP/FADD 0.023 0.071 -10000 0 -0.1 87 87
TRAIL/TRAILR2/FADD 0.017 0.068 -10000 0 -0.11 88 88
cell death -0.007 0.043 -10000 0 -0.099 88 88
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2 -0.017 0.081 -10000 0 -0.18 85 85
TRAILR2 (trimer) 0.033 0.017 -10000 0 0 111 111
CASP8 -0.005 0.12 -10000 0 -0.61 16 16
negative regulation of caspase activity 0 0 -10000 0 -10000 0 0
TRAIL/TRAILR2/FADD/TRADD/RIP 0.033 0.082 -10000 0 -0.11 76 76
BARD1 signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BARD1/CSTF1 0.039 0.053 -10000 0 -0.14 38 38
ATM 0.036 0.014 -10000 0 0 69 69
UBE2D3 0.039 0.009 -10000 0 0 30 30
PRKDC 0.038 0.011 -10000 0 0 44 44
ATR 0.035 0.015 -10000 0 0 84 84
UBE2L3 0.039 0.01 -10000 0 0 34 34
FANCD2 -0.005 0.09 -10000 0 -0.25 58 58
protein ubiquitination 0.01 0.098 -10000 0 -0.13 147 147
XRCC5 0.038 0.011 -10000 0 0 41 41
XRCC6 0.036 0.014 -10000 0 0 69 69
M/R/N Complex 0.048 0.071 -10000 0 -0.15 50 50
MRE11A 0.038 0.012 -10000 0 0 49 49
DNA-PK 0.051 0.067 -10000 0 -0.14 47 47
FA complex/FANCD2/Ubiquitin -0.002 0.12 -10000 0 -0.38 34 34
FANCF 0.04 0.007 -10000 0 0 18 18
BRCA1 0.034 0.015 -10000 0 0 93 93
CCNE1 0.026 0.02 -10000 0 0 202 202
CDK2/Cyclin E1 0.009 0.074 -10000 0 -0.14 97 97
FANCG 0.04 0.007 -10000 0 0 14 14
BRCA1/BACH1/BARD1 0.027 0.068 -10000 0 -0.14 72 72
FANCE 0.04 0.006 -10000 0 0 12 12
FANCC 0.039 0.009 -10000 0 0 25 25
NBN 0.035 0.015 -10000 0 0 87 87
FANCA 0.034 0.016 -10000 0 0 94 94
DNA repair -0.017 0.13 0.26 21 -0.34 43 64
BRCA1/BARD1/ubiquitin 0.027 0.068 -10000 0 -0.14 72 72
BARD1/DNA-PK 0.06 0.083 -10000 0 -0.14 60 60
FANCL 0.037 0.012 -10000 0 0 52 52
mRNA polyadenylation -0.039 0.052 0.14 38 -10000 0 38
BRCA1/BARD1/CTIP/M/R/N Complex -0.024 0.14 0.16 2 -0.28 80 82
BRCA1/BACH1/BARD1/TopBP1 0.038 0.077 -10000 0 -0.13 80 80
BRCA1/BARD1/P53 0.004 0.1 -10000 0 -0.13 182 182
BARD1/CSTF1/BRCA1 0.039 0.072 -10000 0 -0.12 73 73
BRCA1/BACH1 0.034 0.015 -10000 0 0 93 93
BARD1 0.036 0.013 -10000 0 0 64 64
PCNA 0.034 0.015 -10000 0 0 89 89
BRCA1/BARD1/UbcH5C 0.043 0.071 -10000 0 -0.12 73 73
BRCA1/BARD1/UbcH7 0.043 0.07 -10000 0 -0.12 70 70
BRCA1/BARD1/RAD51/PCNA 0.035 0.095 -10000 0 -0.13 115 115
BARD1/DNA-PK/P53 0.02 0.11 -10000 0 -0.13 170 170
BRCA1/BARD1/Ubiquitin 0.027 0.068 -10000 0 -0.14 72 72
BRCA1/BARD1/CTIP 0.015 0.087 0.18 13 -0.13 116 129
FA complex 0.009 0.086 -10000 0 -0.26 34 34
BARD1/EWS 0.041 0.049 -10000 0 -0.13 34 34
RBBP8 -0.015 0.009 -10000 0 -10000 0 0
TP53 0.026 0.02 -10000 0 0 207 207
TOPBP1 0.037 0.012 -10000 0 0 50 50
G1/S transition of mitotic cell cycle -0.003 0.1 0.12 182 -10000 0 182
BRCA1/BARD1 0.014 0.1 -10000 0 -0.13 147 147
CSTF1 0.037 0.013 -10000 0 0 57 57
BARD1/EWS-Fli1 0.019 0.037 -10000 0 -0.12 33 33
CDK2 0.037 0.013 -10000 0 0 56 56
UniProt:Q9BZD1 0 0 -10000 0 -10000 0 0
RAD51 0.035 0.015 -10000 0 0 83 83
RAD50 0.039 0.01 -10000 0 0 35 35
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme 0.027 0.068 -10000 0 -0.14 72 72
EWSR1 0.038 0.012 -10000 0 0 48 48
TCGA08_rtk_signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PDGFRA 0.029 0.019 -10000 0 0 161 161
HRAS 0.039 0.01 -10000 0 0 31 31
EGFR 0.036 0.014 -10000 0 0 67 67
AKT 0.02 0.091 0.21 13 -0.19 35 48
FOXO3 0 0 -10000 0 -10000 0 0
AKT1 0.039 0.01 -10000 0 0 34 34
FOXO1 0 0 -10000 0 -10000 0 0
AKT3 0.03 0.018 -10000 0 0 151 151
FOXO4 0 0 -10000 0 -10000 0 0
MET 0.027 0.02 -10000 0 0 191 191
PIK3CA 0.029 0.019 -10000 0 0 166 166
PIK3CB 0.034 0.016 -10000 0 0 95 95
NRAS 0.039 0.009 -10000 0 0 30 30
PIK3CG 0.033 0.017 -10000 0 0 112 112
PIK3R3 0.034 0.016 -10000 0 0 96 96
PIK3R2 0.036 0.014 -10000 0 0 68 68
NF1 0.034 0.016 -10000 0 0 96 96
RAS 0.002 0.076 0.15 23 -0.23 23 46
ERBB2 0.038 0.012 -10000 0 0 47 47
proliferation/survival/translation -0.021 0.083 0.21 28 -0.21 18 46
PI3K 0.007 0.087 0.17 25 -0.22 39 64
PIK3R1 0.034 0.016 -10000 0 0 99 99
KRAS 0.034 0.016 -10000 0 0 95 95
FOXO 0.039 0.053 0.17 24 -10000 0 24
AKT2 0.037 0.012 -10000 0 0 54 54
PTEN 0.038 0.01 -10000 0 0 36 36
Paxillin-dependent events mediated by a4b1

Figure S19.  Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S19.  Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CRKL 0.038 0.01 -10000 0 0 36 36
Rac1/GDP 0.032 0.025 -10000 0 -0.024 67 67
DOCK1 0.037 0.012 -10000 0 0 53 53
ITGA4 0.035 0.015 -10000 0 0 88 88
RAC1 0.039 0.009 -10000 0 0 28 28
alpha4/beta7 Integrin 0.031 0.065 -10000 0 -0.14 66 66
mol:GTP 0 0 -10000 0 -10000 0 0
CRK 0.038 0.012 -10000 0 0 49 49
alpha4/beta1 Integrin 0.045 0.063 -10000 0 -0.12 53 53
alpha4/beta7 Integrin/Paxillin 0.051 0.07 0.18 56 -0.11 53 109
lamellipodium assembly -0.025 0.14 -10000 0 -0.36 65 65
PIK3CA 0.029 0.019 -10000 0 0 166 166
PI3K 0.023 0.06 -10000 0 -0.15 44 44
ARF6 0.04 0.007 -10000 0 0 16 16
TLN1 0.038 0.011 -10000 0 0 39 39
PXN -0.017 0.008 -10000 0 -10000 0 0
PIK3R1 0.034 0.016 -10000 0 0 99 99
ARF6/GTP 0.061 0.071 -10000 0 -0.11 54 54
cell adhesion 0.06 0.079 0.19 50 -0.11 65 115
CRKL/CBL 0.055 0.02 -10000 0 -0.13 1 1
alpha4/beta1 Integrin/Paxillin 0.05 0.068 0.18 52 -0.11 52 104
ITGB1 0.038 0.01 -10000 0 0 36 36
ITGB7 0.038 0.01 -10000 0 0 38 38
ARF6/GDP 0.033 0.025 -10000 0 -0.024 66 66
alpha4/beta1 Integrin/Paxillin/VCAM1 0.021 0.095 0.2 29 -0.13 121 150
p130Cas/Crk/Dock1 0.056 0.052 -10000 0 -0.12 27 27
VCAM1 0.02 0.021 -10000 0 0 281 281
alpha4/beta1 Integrin/Paxillin/Talin 0.062 0.08 0.2 50 -0.11 65 115
alpha4/beta1 Integrin/Paxillin/GIT1 0.067 0.073 0.2 48 -0.11 52 100
BCAR1 0.036 0.013 -10000 0 0 65 65
mol:GDP -0.065 0.072 0.11 52 -0.19 48 100
CBL 0.04 0.008 -10000 0 0 20 20
PRKACA 0.035 0.015 -10000 0 0 84 84
GIT1 0.039 0.009 -10000 0 0 25 25
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton 0.062 0.08 0.2 50 -0.11 65 115
Rac1/GTP -0.03 0.16 -10000 0 -0.4 65 65
Nongenotropic Androgen signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PTK2 -0.007 0.005 0 182 -10000 0 182
GNB1/GNG2 0.039 0.068 -10000 0 -0.11 83 83
regulation of S phase of mitotic cell cycle -0.011 0.075 -10000 0 -0.17 83 83
GNAO1 0.035 0.015 -10000 0 0 85 85
HRAS 0.039 0.01 -10000 0 0 31 31
SHBG/T-DHT 0.026 0.007 -10000 0 -10000 0 0
PELP1 0.038 0.011 -10000 0 0 39 39
AKT1 -0.009 0.003 0.002 41 -10000 0 41
MAP2K1 -0.034 0.078 0.17 23 -0.17 77 100
T-DHT/AR 0.006 0.053 -10000 0 -0.12 75 75
G-protein coupled receptor activity 0 0 -10000 0 -10000 0 0
mol:GTP -0.001 0.003 -10000 0 -0.007 100 100
GNAI2 0.04 0.006 -10000 0 0 13 13
GNAI3 0.038 0.011 -10000 0 0 45 45
GNAI1 0.034 0.015 -10000 0 0 93 93
mol:GDP -0.039 0.085 -10000 0 -0.25 66 66
cell proliferation -0.069 0.17 0.24 7 -0.4 103 110
PIK3CA 0.029 0.019 -10000 0 0 166 166
FOS -0.12 0.29 0.28 2 -0.7 103 105
mol:Ca2+ -0.007 0.021 -10000 0 -0.048 83 83
MAPK3 -0.052 0.13 0.23 7 -0.3 94 101
MAPK1 -0.038 0.13 -10000 0 -0.42 33 33
PIK3R1 0.034 0.016 -10000 0 0 99 99
mol:IP3 0 0.002 0.002 12 -0.004 100 112
cAMP biosynthetic process -0.001 0.024 0.2 4 -10000 0 4
GNG2 0.039 0.009 -10000 0 0 29 29
potassium channel inhibitor activity 0 0.002 0.002 12 -0.004 100 112
HRAS/GTP 0.025 0.076 -10000 0 -0.09 137 137
actin cytoskeleton reorganization 0.027 0.05 -10000 0 -0.11 43 43
SRC 0.039 0.009 -10000 0 0 28 28
voltage-gated calcium channel activity 0 0.002 0.002 12 -0.004 100 112
PI3K 0.022 0.051 -10000 0 -0.12 44 44
apoptosis 0.059 0.18 0.39 110 -0.23 3 113
T-DHT/AR/PELP1 0.025 0.056 -10000 0 -0.11 75 75
HRAS/GDP -0.002 0.11 0.15 1 -0.24 67 68
CREB1 -0.074 0.18 0.25 1 -0.42 110 111
RAC1-CDC42/GTP 0.037 0.057 -10000 0 -0.11 43 43
AR 0.032 0.017 -10000 0 0 118 118
GNB1 0.039 0.01 -10000 0 0 33 33
RAF1 -0.021 0.074 0.18 24 -0.18 15 39
RAC1-CDC42/GDP 0.02 0.11 -10000 0 -0.24 65 65
T-DHT/AR/PELP1/Src 0.039 0.064 -10000 0 -0.1 72 72
MAP2K2 -0.028 0.074 0.17 22 -0.17 64 86
T-DHT/AR/PELP1/Src/PI3K -0.011 0.075 -10000 0 -0.17 83 83
GNAZ 0.038 0.011 -10000 0 0 46 46
SHBG 0.038 0.01 -10000 0 0 37 37
Gi family/GNB1/GNG2/GDP -0.007 0.11 -10000 0 -0.31 36 36
mol:T-DHT 0 0.001 -10000 0 -0.003 25 25
RAC1 0.039 0.009 -10000 0 0 28 28
GNRH1 -0.008 0.004 0 107 -10000 0 107
Gi family/GTP -0.019 0.077 -10000 0 -0.18 73 73
CDC42 0.04 0.007 -10000 0 0 18 18
Signaling events mediated by the Hedgehog family

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
TGFB2 -0.066 0.18 -10000 0 -0.39 122 122
IHH 0.021 0.066 -10000 0 -0.098 126 126
SHH Np/Cholesterol/GAS1 0.027 0.025 -10000 0 -0.1 12 12
LRPAP1 0.036 0.014 -10000 0 0 72 72
dorsoventral neural tube patterning -0.027 0.025 0.1 12 -10000 0 12
SMO/beta Arrestin2 0.015 0.12 0.24 2 -0.2 104 106
SMO -0.004 0.11 -10000 0 -0.2 109 109
AKT1 -0.015 0.13 -10000 0 -0.4 35 35
ARRB2 0.038 0.011 -10000 0 0 46 46
BOC 0.035 0.015 -10000 0 0 82 82
ADRBK1 0.041 0.004 -10000 0 0 6 6
heart looping -0.003 0.11 -10000 0 -0.2 109 109
STIL -0.002 0.096 0.21 26 -0.17 104 130
DHH N/PTCH2 0.058 0.014 -10000 0 -10000 0 0
DHH N/PTCH1 0.002 0.11 -10000 0 -0.19 125 125
PIK3CA 0.029 0.019 -10000 0 0 166 166
DHH 0.04 0.006 -10000 0 0 11 11
PTHLH -0.057 0.16 -10000 0 -0.38 108 108
determination of left/right symmetry -0.003 0.11 -10000 0 -0.2 109 109
PIK3R1 0.034 0.016 -10000 0 0 99 99
skeletal system development -0.056 0.16 -10000 0 -0.37 108 108
IHH N/Hhip 0.034 0.054 -10000 0 -0.15 1 1
DHH N/Hhip 0.055 0.02 -10000 0 -0.13 1 1
mol:Cholesterol 0 0 -10000 0 -10000 0 0
heart development -0.003 0.11 -10000 0 -0.2 109 109
pancreas development 0.038 0.011 -10000 0 0 44 44
HHAT 0.039 0.009 -10000 0 0 25 25
PI3K 0.023 0.06 -10000 0 -0.15 44 44
EntrezGene:84976 0 0 -10000 0 -10000 0 0
GAS1 0.036 0.013 -10000 0 0 66 66
somite specification -0.003 0.11 -10000 0 -0.2 109 109
SHH Np/Cholesterol/PTCH1 -0.007 0.085 -10000 0 -0.17 109 109
SHH Np/Cholesterol/PTCH2 0.032 0.015 -10000 0 -0.1 1 1
SHH Np/Cholesterol/Megalin 0.021 0.028 -10000 0 -0.1 15 15
SHH -0.018 0.007 -10000 0 -10000 0 0
catabolic process -0.037 0.095 -10000 0 -0.21 126 126
SMO/Vitamin D3 -0.007 0.1 0.2 17 -0.2 106 123
SHH Np/Cholesterol/Hhip 0.031 0.017 -10000 0 -0.1 2 2
LRP2 0.029 0.019 -10000 0 0 160 160
receptor-mediated endocytosis 0 0.1 0.19 18 -0.18 102 120
SHH Np/Cholesterol/BOC 0.026 0.027 -10000 0 -0.1 16 16
SHH Np/Cholesterol/CDO 0.023 0.033 -10000 0 -0.1 27 27
mesenchymal cell differentiation -0.03 0.017 0.1 2 -10000 0 2
mol:Vitamin D3 -0.015 0.086 0.2 20 -0.17 108 128
IHH N/PTCH2 0.037 0.054 -10000 0 -0.059 121 121
CDON 0.034 0.015 -10000 0 0 91 91
IHH N/PTCH1 -0.021 0.11 -10000 0 -0.21 126 126
Megalin/LRPAP1 0.027 0.054 -10000 0 -0.14 40 40
PTCH2 0.04 0.008 -10000 0 0 19 19
SHH Np/Cholesterol 0.031 0.041 0.2 31 -0.097 1 32
PTCH1 -0.037 0.096 -10000 0 -0.21 126 126
HHIP 0.038 0.011 -10000 0 0 44 44
Integrins in angiogenesis

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer 0.028 0.013 -10000 0 -0.12 3 3
alphaV beta3 Integrin 0.029 0.078 -10000 0 -0.12 91 91
PTK2 -0.014 0.13 0.26 5 -0.28 70 75
IGF1R 0.033 0.017 -10000 0 0 112 112
PI4KB 0 0 -10000 0 -10000 0 0
MFGE8 0.031 0.018 -10000 0 0 137 137
SRC 0.039 0.009 -10000 0 0 28 28
CDKN1B 0.003 0.087 -10000 0 -0.33 29 29
VEGFA 0 0 -10000 0 -10000 0 0
ILK 0.016 0.056 -10000 0 -0.27 12 12
ROCK1 0.04 0.008 -10000 0 0 21 21
AKT1 0.007 0.051 0.21 4 -0.26 11 15
PTK2B -0.014 0.06 0.19 12 -0.18 13 25
alphaV/beta3 Integrin/JAM-A 0.039 0.078 0.2 6 -0.12 85 91
CBL 0.04 0.008 -10000 0 0 20 20
mol:GTP 0 0 -10000 0 -10000 0 0
alphaV beta3 Integrin/ANGPTL3 0.031 0.079 -10000 0 -0.13 91 91
IGF-1R heterotetramer/IGF1/IRS1/Shp2 0.054 0.083 -10000 0 -0.12 85 85
VEGF/Rho/ROCK/alphaV/beta3 Integrin -0.004 0.084 -10000 0 -0.17 94 94
alphaV/beta3 Integrin/Syndecan-1 0.029 0.079 -10000 0 -0.12 94 94
PI4KA 0 0 -10000 0 -10000 0 0
IGF-1R heterotetramer/IGF1/IRS1 -0.018 0.1 -10000 0 -0.14 173 173
PI4 Kinase 0 0 -10000 0 -10000 0 0
PIK3CA 0.029 0.019 -10000 0 0 166 166
alphaV/beta3 Integrin/Osteopontin 0.007 0.098 -10000 0 -0.15 128 128
RPS6KB1 -0.033 0.1 0.27 13 -0.2 58 71
TLN1 0.038 0.011 -10000 0 0 39 39
MAPK3 -0.049 0.15 0.22 3 -0.33 112 115
GPR124 0.037 0.012 -10000 0 0 55 55
MAPK1 -0.048 0.15 0.22 3 -0.34 108 111
PXN 0.04 0.006 -10000 0 0 10 10
PIK3R1 0.034 0.016 -10000 0 0 99 99
alphaV/beta3 Integrin/Tumstatin 0.031 0.079 -10000 0 -0.13 91 91
cell adhesion -0.003 0.098 -10000 0 -0.16 128 128
ANGPTL3 0.04 0.007 -10000 0 0 15 15
VEGFR2 homodimer/VEGFA homodimer/Src 0.05 0.019 -10000 0 -0.11 2 2
IGF-1R heterotetramer 0.033 0.017 -10000 0 0 112 112
Rac1/GDP 0.029 0.009 -10000 0 -0.12 1 1
TGFBR2 0.039 0.01 -10000 0 0 34 34
ITGB3 0.032 0.017 -10000 0 0 116 116
IGF1 0.035 0.014 -10000 0 0 77 77
RAC1 0.039 0.009 -10000 0 0 28 28
regulation of cell-matrix adhesion 0.03 0.075 -10000 0 -0.12 82 82
apoptosis 0.033 0.016 -10000 0 0 110 110
CD47 0.036 0.013 -10000 0 0 65 65
alphaV/beta3 Integrin/CD47 0.023 0.086 -10000 0 -0.14 99 99
VCL 0.039 0.01 -10000 0 0 34 34
alphaV/beta3 Integrin/Del1 0.007 0.082 -10000 0 -0.13 113 113
CSF1 0.035 0.015 -10000 0 0 84 84
PIK3C2A -0.004 0.1 -10000 0 -0.34 43 43
PI4 Kinase/Pyk2 0.006 0.055 -10000 0 -0.11 81 81
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin 0.029 0.073 -10000 0 -0.11 94 94
FAK1/Vinculin 0.005 0.12 0.26 6 -0.24 70 76
alphaV beta3/Integrin/ppsTEM5 0.031 0.075 -10000 0 -0.12 82 82
RHOA 0.04 0.006 -10000 0 0 13 13
VTN 0.039 0.008 -10000 0 0 24 24
BCAR1 0.036 0.013 -10000 0 0 65 65
FGF2 0.039 0.01 -10000 0 0 33 33
F11R -0.019 0.006 -10000 0 -10000 0 0
alphaV/beta3 Integrin/Lactadherin 0.01 0.088 -10000 0 -0.14 123 123
alphaV/beta3 Integrin/TGFBR2 0.027 0.084 -10000 0 -0.14 94 94
alphaV/beta3 Integrin/c-FMS/Cbl/Cas 0.047 0.089 -10000 0 -0.13 93 93
HSP90AA1 0 0 -10000 0 -10000 0 0
alphaV/beta3 Integrin/Talin 0.026 0.077 -10000 0 -0.12 101 101
mol:GDP 0 0 -10000 0 -10000 0 0
FN1 0.021 0.021 -10000 0 0 268 268
alphaV/beta3 Integrin/Pyk2 0.018 0.067 0.21 1 -0.11 89 90
SDC1 0.039 0.009 -10000 0 0 25 25
VAV3 -0.031 0.072 0.21 15 -0.21 36 51
PTPN11 0.039 0.009 -10000 0 0 29 29
IRS1 0.04 0.008 -10000 0 0 22 22
FAK1/Paxillin 0.007 0.12 0.26 6 -0.24 71 77
cell migration -0.004 0.11 0.25 6 -0.22 70 76
ITGAV 0.033 0.017 -10000 0 0 110 110
PI3K 0.026 0.087 -10000 0 -0.14 68 68
SPP1 0.031 0.018 -10000 0 0 139 139
KDR 0.039 0.009 -10000 0 0 27 27
mol:PI-4-5-P2 0 0 -10000 0 -10000 0 0
alphaV/beta3 Integrin/Caspase 8 0.033 0.017 -10000 0 0 110 110
COL4A3 0.041 0.005 -10000 0 0 7 7
angiogenesis -0.053 0.17 0.26 3 -0.37 111 114
Rac1/GTP -0.033 0.075 0.21 15 -0.2 34 49
EDIL3 0.027 0.02 -10000 0 0 185 185
cell proliferation 0.027 0.083 -10000 0 -0.14 94 94
Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1 0.015 0.14 -10000 0 -0.34 29 29
MAP3K8 0.039 0.009 -10000 0 0 24 24
FOS 0.015 0.1 -10000 0 -0.3 21 21
PRKCA 0.026 0.029 -10000 0 -0.015 167 167
PTPN7 0.03 0.032 0.071 1 -0.031 109 110
HRAS 0.039 0.01 -10000 0 0 31 31
PRKCB 0 0.007 0.01 93 -0.013 100 193
NRAS 0.039 0.009 -10000 0 0 30 30
RAS family/GTP 0.053 0.05 -10000 0 -0.11 27 27
MAPK3 0.029 0.078 -10000 0 -0.43 8 8
MAP2K1 0 0.092 0.16 3 -0.27 44 47
ELK1 0.027 0.031 -10000 0 -0.038 101 101
BRAF -0.002 0.065 -10000 0 -0.28 26 26
mol:GTP 0 0.002 0.002 84 -0.004 100 184
MAPK1 0.015 0.1 -10000 0 -0.38 26 26
RAF1 -0.007 0.074 -10000 0 -0.28 35 35
KRAS 0.034 0.016 -10000 0 0 95 95
IL1-mediated signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
UBC13/UEV1A 0.028 0.019 -10000 0 -0.12 8 8
PRKCZ 0.039 0.009 -10000 0 0 27 27
MAP3K7IP2 0.037 0.012 -10000 0 0 53 53
ERC1 0 0 -10000 0 -10000 0 0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4 -0.034 0.13 -10000 0 -0.29 95 95
IRAK/TOLLIP 0.038 0.026 0.19 3 -0.1 10 13
IKBKB 0.038 0.011 -10000 0 0 41 41
IKBKG 0.041 0.002 -10000 0 0 2 2
IL1 alpha/IL1R2 0.046 0.038 -10000 0 -0.13 16 16
IL1A 0.039 0.009 -10000 0 0 30 30
IL1B -0.012 0.01 -10000 0 -10000 0 0
IRAK/TRAF6/p62/Atypical PKCs 0.043 0.076 0.22 2 -0.12 61 63
IL1R2 0.035 0.015 -10000 0 0 80 80
IL1R1 0.031 0.018 -10000 0 0 141 141
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP -0.045 0.14 -10000 0 -0.3 92 92
TOLLIP 0.039 0.01 -10000 0 0 32 32
TICAM2 0.037 0.012 -10000 0 0 51 51
MAP3K3 0.04 0.007 -10000 0 0 14 14
TAK1/TAB1/TAB2 0.061 0.054 -10000 0 -0.14 26 26
IKK complex/ELKS 0.013 0.084 0.28 1 -0.27 25 26
JUN -0.037 0.056 0.16 16 -0.19 17 33
MAP3K7 0.038 0.01 -10000 0 0 38 38
IL1 beta fragment/IL1R1/IL1RAP/PI3K 0 0.11 -10000 0 -0.17 121 121
IL1 alpha/IL1R1/IL1RAP/MYD88 0.037 0.084 -10000 0 -0.12 91 91
PIK3R1 0.034 0.016 -10000 0 0 99 99
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4 0.038 0.098 -10000 0 -0.13 100 100
IL1 beta fragment/IL1R1/IL1RAP -0.011 0.096 0.18 6 -0.15 147 153
NFKB1 0.036 0.013 -10000 0 0 66 66
MAPK8 -0.029 0.052 0.17 15 -0.2 16 31
IRAK1 0.016 0.014 0.069 1 -0.11 6 7
IL1RN/IL1R1 0.022 0.07 -10000 0 -0.14 81 81
IRAK4 0.036 0.014 -10000 0 0 68 68
PRKCI 0.027 0.02 -10000 0 0 192 192
TRAF6 0.04 0.008 -10000 0 0 19 19
PI3K 0.023 0.06 -10000 0 -0.15 44 44
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP -0.036 0.14 0.17 1 -0.31 96 97
CHUK 0.038 0.011 -10000 0 0 46 46
IL1 beta fragment/IL1R1/IL1RAP/MYD88s -0.011 0.096 0.18 6 -0.15 147 153
IL1 beta/IL1R2 -0.004 0.088 0.24 1 -0.15 131 132
IRAK/TRAF6/TAK1/TAB1/TAB2 0.071 0.068 0.22 1 -0.14 32 33
NF kappa B1 p50/RelA -0.011 0.11 -10000 0 -0.18 116 116
IRAK3 0.034 0.015 -10000 0 0 93 93
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4 0.003 0.12 -10000 0 -0.16 137 137
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP -0.015 0.099 -10000 0 -0.2 97 97
IL1 alpha/IL1R1/IL1RAP 0.017 0.077 -10000 0 -0.13 91 91
RELA 0.04 0.006 -10000 0 0 10 10
MAP3K7IP1 0.037 0.012 -10000 0 0 51 51
SQSTM1 0.038 0.011 -10000 0 0 46 46
MYD88 0.04 0.006 -10000 0 0 12 12
IRAK/TRAF6/MEKK3 0.06 0.036 0.21 3 -0.11 18 21
IL1RAP 0.027 0.02 -10000 0 0 185 185
UBE2N 0.04 0.007 -10000 0 0 16 16
IRAK/TRAF6 -0.022 0.094 -10000 0 -0.16 134 134
CASP1 0.027 0.019 -10000 0 0 184 184
IL1RN/IL1R2 0.041 0.048 -10000 0 -0.14 30 30
IL1 beta fragment/IL1R1/IL1RAP/MYD88 0.002 0.1 0.2 6 -0.15 140 146
TMEM189-UBE2V1 0 0 -10000 0 -10000 0 0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP -0.023 0.13 0.21 1 -0.28 94 95
PIK3CA 0.029 0.019 -10000 0 0 166 166
IL1RN 0.038 0.011 -10000 0 0 39 39
TRAF6/TAK1/TAB1/TAB2 0.072 0.066 -10000 0 -0.14 32 32
MAP2K6 -0.025 0.053 0.19 15 -0.2 13 28
IL23-mediated signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CCL2 -0.17 0.61 -10000 0 -1.2 120 120
IL23A -0.11 0.55 -10000 0 -1.2 80 80
NF kappa B1 p50/RelA/I kappa B alpha -0.11 0.54 -10000 0 -1.2 86 86
positive regulation of T cell mediated cytotoxicity -0.13 0.61 -10000 0 -1.3 89 89
ITGA3 -0.16 0.58 -10000 0 -1.1 115 115
IL17F -0.041 0.36 0.49 7 -0.7 87 94
IL12B 0.033 0.072 0.16 8 -0.082 2 10
STAT1 (dimer) -0.15 0.58 -10000 0 -1.3 88 88
CD4 -0.12 0.57 0.66 2 -1.2 96 98
IL23 -0.11 0.52 -10000 0 -1.2 79 79
IL23R 0.037 0.14 -10000 0 -1.2 3 3
IL1B -0.13 0.59 -10000 0 -1.3 93 93
T-helper cell lineage commitment 0 0 -10000 0 -10000 0 0
IL24 -0.099 0.51 -10000 0 -1.1 80 80
TYK2 0.024 0.055 0.13 2 -10000 0 2
STAT4 0.039 0.008 -10000 0 0 24 24
STAT3 0.038 0.011 -10000 0 0 41 41
IL18RAP 0.041 0.007 -10000 0 0 15 15
IL12RB1 0.023 0.057 0.13 3 -10000 0 3
PIK3CA 0.029 0.019 -10000 0 0 166 166
IL12Rbeta1/TYK2 0.035 0.068 -10000 0 -10000 0 0
IL23R/JAK2 0.047 0.17 -10000 0 -1.2 3 3
positive regulation of chronic inflammatory response -0.13 0.61 -10000 0 -1.3 89 89
natural killer cell activation -0.002 0.009 -10000 0 -10000 0 0
JAK2 0.031 0.068 0.16 8 -0.081 3 11
PIK3R1 0.034 0.016 -10000 0 0 99 99
NFKB1 0.038 0.015 -10000 0 0 66 66
RELA 0.042 0.008 -10000 0 0 10 10
positive regulation of dendritic cell antigen processing and presentation -0.098 0.5 -10000 0 -1.1 79 79
ALOX12B -0.099 0.51 -10000 0 -1.1 82 82
CXCL1 -0.13 0.57 -10000 0 -1.2 104 104
T cell proliferation -0.13 0.61 -10000 0 -1.3 89 89
NFKBIA 0.038 0.015 -10000 0 0 64 64
IL17A -0.025 0.3 0.42 10 -0.54 88 98
PI3K -0.15 0.53 -10000 0 -1.2 86 86
IFNG 0.007 0.038 0.1 5 -0.1 13 18
STAT3 (dimer) -0.14 0.5 -10000 0 -1.1 87 87
IL18R1 0.041 0.008 -10000 0 0 19 19
IL23/IL23R/JAK2/TYK2/SOCS3 -0.015 0.34 0.5 4 -0.66 74 78
IL18/IL18R 0.049 0.067 -10000 0 -0.11 61 61
macrophage activation -0.007 0.021 0.033 1 -0.045 74 75
TNF -0.11 0.54 -10000 0 -1.2 80 80
STAT3/STAT4 -0.12 0.56 -10000 0 -1.2 87 87
STAT4 (dimer) -0.13 0.58 -10000 0 -1.3 87 87
IL18 0.031 0.019 -10000 0 0 148 148
IL19 -0.099 0.51 -10000 0 -1.1 81 81
STAT5A (dimer) -0.13 0.58 -10000 0 -1.3 88 88
STAT1 0.034 0.016 -10000 0 0 102 102
SOCS3 0.036 0.013 -10000 0 0 63 63
CXCL9 -0.16 0.61 -10000 0 -1.2 120 120
MPO -0.099 0.51 -10000 0 -1.1 82 82
positive regulation of humoral immune response -0.13 0.61 -10000 0 -1.3 89 89
IL23/IL23R/JAK2/TYK2 -0.17 0.65 -10000 0 -1.4 89 89
IL6 -0.1 0.53 -10000 0 -1.2 84 84
STAT5A 0.038 0.01 -10000 0 0 36 36
IL2 0.039 0.016 -10000 0 -0.032 12 12
positive regulation of tyrosine phosphorylation of STAT protein -0.002 0.009 -10000 0 -10000 0 0
CD3E -0.11 0.54 0.68 1 -1.2 87 88
keratinocyte proliferation -0.13 0.61 -10000 0 -1.3 89 89
NOS2 -0.1 0.51 -10000 0 -1.1 89 89
Signaling events mediated by PTP1B

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
PDGFRB 0.036 0.013 -10000 0 0 65 65
Jak2/Leptin Receptor -0.019 0.15 0.25 1 -0.4 54 55
PTP1B/AKT1 -0.034 0.11 -10000 0 -0.24 87 87
FYN 0.034 0.016 -10000 0 0 94 94
p210 bcr-abl/PTP1B -0.052 0.11 -10000 0 -0.25 95 95
EGFR 0.036 0.017 -10000 0 -0.004 76 76
EGF/EGFR -0.025 0.12 -10000 0 -0.23 90 90
CSF1 0.035 0.015 -10000 0 0 84 84
AKT1 0.039 0.01 -10000 0 0 34 34
INSR 0.038 0.012 -10000 0 0 49 49
PTP1B/N-cadherin -0.054 0.12 -10000 0 -0.24 125 125
Insulin Receptor/Insulin -0.008 0.12 -10000 0 -0.22 64 64
HCK 0.036 0.013 -10000 0 0 65 65
CRK 0.038 0.012 -10000 0 0 49 49
TYK2 -0.037 0.12 0.23 24 -0.25 79 103
EGF 0.037 0.016 -10000 0 -0.009 52 52
YES1 0.037 0.012 -10000 0 0 51 51
CAV1 -0.036 0.11 0.19 1 -0.24 77 78
TXN 0.037 0.012 -10000 0 0 49 49
PTP1B/IRS1/GRB2 -0.027 0.13 -10000 0 -0.24 95 95
cell migration 0.052 0.11 0.25 95 -10000 0 95
STAT3 0.038 0.011 -10000 0 0 41 41
PRLR 0.038 0.016 -10000 0 -10000 0 0
ITGA2B 0.039 0.008 -10000 0 0 22 22
CSF1R 0.034 0.016 -10000 0 0 94 94
Prolactin Receptor/Prolactin 0.056 0.028 -10000 0 -10000 0 0
FGR 0.04 0.007 -10000 0 0 15 15
PTP1B/p130 Cas -0.035 0.12 -10000 0 -0.24 91 91
Crk/p130 Cas -0.028 0.12 -10000 0 -0.24 87 87
DOK1 -0.038 0.11 0.21 2 -0.24 75 77
JAK2 -0.031 0.14 -10000 0 -0.41 56 56
Jak2/Leptin Receptor/Leptin -0.026 0.14 -10000 0 -0.28 80 80
PIK3R1 0.034 0.016 -10000 0 0 99 99
PTPN1 -0.053 0.11 -10000 0 -0.25 95 95
LYN 0.035 0.015 -10000 0 0 83 83
CDH2 0.019 0.021 -10000 0 0 290 290
SRC 0.003 0.1 -10000 0 -0.5 17 17
ITGB3 0.032 0.017 -10000 0 0 116 116
CAT1/PTP1B -0.041 0.13 0.22 7 -0.28 81 88
CAPN1 0.038 0.009 -10000 0 0 25 25
CSK 0.039 0.009 -10000 0 0 25 25
PI3K -0.012 0.11 -10000 0 -0.23 49 49
mol:H2O2 0.002 0.005 -10000 0 -10000 0 0
STAT3 (dimer) -0.022 0.14 -10000 0 -0.26 76 76
negative regulation of transcription -0.03 0.14 -10000 0 -0.4 56 56
FCGR2A 0.032 0.017 -10000 0 0 119 119
FER 0.037 0.011 -10000 0 0 44 44
alphaIIb/beta3 Integrin 0.037 0.05 -10000 0 -0.14 35 35
BLK 0.033 0.017 -10000 0 0 114 114
Insulin Receptor/Insulin/Shc 0.068 0.036 -10000 0 -0.12 5 5
RHOA 0.039 0.006 -10000 0 0 13 13
LEPR 0.039 0.011 -10000 0 0 40 40
BCAR1 0.036 0.013 -10000 0 0 65 65
p210 bcr-abl/Grb2 0.04 0.008 -10000 0 0 21 21
mol:NADPH -0.001 0.002 -10000 0 -10000 0 0
TRPV6 -0.011 0.12 0.2 3 -0.3 49 52
PRL 0.042 0.011 -10000 0 -10000 0 0
SOCS3 -0.029 0.27 -10000 0 -1.2 28 28
SPRY2 0.023 0.021 -10000 0 0 240 240
Insulin Receptor/Insulin/IRS1 0.068 0.038 -10000 0 -0.12 8 8
CSF1/CSF1R -0.043 0.14 -10000 0 -0.26 100 100
Ras protein signal transduction 0.011 0.091 0.6 11 -10000 0 11
IRS1 0.04 0.008 -10000 0 0 22 22
INS 0.039 0.01 -10000 0 0 30 30
LEP 0.039 0.008 -10000 0 0 22 22
STAT5B -0.041 0.13 -10000 0 -0.27 87 87
STAT5A -0.043 0.13 -10000 0 -0.27 88 88
GRB2 0.04 0.008 -10000 0 0 21 21
PDGFB-D/PDGFRB -0.042 0.12 -10000 0 -0.24 94 94
CSN2 0.039 0.06 0.43 1 -10000 0 1
PIK3CA 0.029 0.019 -10000 0 0 166 166
LAT -0.059 0.19 -10000 0 -0.48 85 85
YBX1 0.049 0.019 -10000 0 -0.28 1 1
LCK 0.039 0.009 -10000 0 0 25 25
SHC1 0.039 0.008 -10000 0 0 23 23
NOX4 0.021 0.021 -10000 0 0 277 277
IGF1 pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
NCK2 0.041 0.004 -10000 0 0 6 6
PTK2 0.027 0.019 -10000 0 0 182 182
CRKL -0.022 0.051 0.11 12 -0.13 68 80
GRB2/SOS1/SHC 0.065 0.049 -10000 0 -0.12 24 24
HRAS 0.039 0.01 -10000 0 0 31 31
IRS1/Crk 0.011 0.056 -10000 0 -0.12 73 73
IGF-1R heterotetramer/IGF1/PTP1B 0.034 0.07 -10000 0 -0.12 70 70
AKT1 0.008 0.096 0.18 101 -0.17 15 116
BAD 0.001 0.09 0.16 100 -0.17 14 114
mol:GTP 0 0 -10000 0 -10000 0 0
CRK -0.02 0.051 0.12 13 -0.13 64 77
IGF-1R heterotetramer/IGF1/IRS1/Shp2 0.013 0.07 0.2 8 -0.13 84 92
RAF1 0.024 0.12 0.28 15 -0.51 11 26
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos 0.045 0.085 0.21 3 -0.13 83 86
YWHAZ 0.034 0.016 -10000 0 0 96 96
IGF-1R heterotetramer/IGF1/IRS1 0.019 0.067 0.18 3 -0.13 82 85
PIK3CA 0.029 0.019 -10000 0 0 166 166
RPS6KB1 0.009 0.098 0.18 105 -0.18 17 122
GNB2L1 0.039 0.009 -10000 0 0 30 30
positive regulation of MAPKKK cascade 0.023 0.11 0.27 20 -0.41 10 30
PXN 0.04 0.006 -10000 0 0 10 10
PIK3R1 0.034 0.016 -10000 0 0 99 99
cell adhesion 0 0 -10000 0 -10000 0 0
GRB2/SOS1 0.047 0.044 -10000 0 -0.14 24 24
HRAS/GTP 0.015 0.065 -10000 0 -0.13 75 75
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc 0.063 0.087 -10000 0 -0.12 77 77
IGF-1R heterotetramer 0.034 0.023 0.099 3 -0.054 13 16
IGF-1R heterotetramer/IGF1/IRS/Nck 0.035 0.075 0.19 3 -0.12 82 85
Crk/p130 Cas/Paxillin 0.043 0.081 0.25 9 -0.13 70 79
IGF1R 0.034 0.023 0.099 3 -0.054 13 16
IGF1 0.027 0.034 0.099 3 -0.053 67 70
IRS2/Crk 0.01 0.054 0.17 3 -0.13 59 62
PI3K 0.023 0.079 0.21 1 -0.12 88 89
apoptosis -0.008 0.094 0.17 8 -0.18 83 91
HRAS/GDP 0.029 0.007 -10000 0 -10000 0 0
PRKCD -0.014 0.092 0.21 3 -0.22 65 68
RAF1/14-3-3 E 0.036 0.12 0.28 14 -0.44 11 25
BAD/14-3-3 0.008 0.097 0.19 83 -0.17 14 97
PRKCZ 0.007 0.095 0.18 100 -0.17 15 115
Crk/p130 Cas/Paxillin/FAK1 0.016 0.08 0.19 18 -0.16 35 53
PTPN1 0.037 0.012 -10000 0 0 55 55
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1 -0.012 0.095 -10000 0 -0.22 67 67
BCAR1 0.036 0.013 -10000 0 0 65 65
IGF-1R heterotetramer/IGF1/SHC/GRB10 0.056 0.076 -10000 0 -0.11 72 72
mol:GDP 0 0 -10000 0 -10000 0 0
SOS1 0.037 0.012 -10000 0 0 51 51
IRS1/NCK2 0.025 0.067 0.14 15 -0.12 82 97
GRB10 0.04 0.008 -10000 0 0 22 22
PTPN11 -0.02 0.052 0.12 13 -0.13 66 79
IRS1 0.005 0.06 0.13 17 -0.13 80 97
IRS2 -0.021 0.051 0.12 14 -0.13 67 81
IGF-1R heterotetramer/IGF1 0.021 0.074 0.16 3 -0.16 72 75
GRB2 0.04 0.008 -10000 0 0 21 21
PDPK1 0.015 0.1 0.19 103 -0.18 14 117
YWHAE 0.037 0.013 -10000 0 0 58 58
PRKD1 -0.016 0.095 0.21 1 -0.22 69 70
SHC1 0.039 0.008 -10000 0 0 23 23
IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1 0.027 0.1 0.21 15 -0.24 33 48
TBX21 -0.026 0.27 -10000 0 -0.69 51 51
B2M 0.038 0.013 -10000 0 -10000 0 0
TYK2 0.024 0.043 -10000 0 -0.048 101 101
IL12RB1 0.023 0.044 -10000 0 -0.049 107 107
GADD45B -0.058 0.34 -10000 0 -0.88 58 58
IL12RB2 0.027 0.045 -10000 0 -0.048 111 111
GADD45G -0.032 0.3 -10000 0 -0.72 59 59
natural killer cell activation 0.002 0.021 0.043 11 -0.033 96 107
RELB 0.039 0.01 -10000 0 0 33 33
RELA 0.04 0.006 -10000 0 0 10 10
IL18 0.03 0.024 -10000 0 -0.042 19 19
IL2RA 0.038 0.01 -10000 0 0 38 38
IFNG 0.037 0.013 -10000 0 0 58 58
STAT3 (dimer) -0.025 0.28 0.4 2 -0.57 84 86
HLA-DRB5 0.016 0.027 -10000 0 -0.006 297 297
FASLG -0.025 0.28 0.52 1 -0.71 49 50
NF kappa B2 p52/RelB -0.013 0.28 -10000 0 -0.56 84 84
CD4 0.025 0.028 -10000 0 -0.013 179 179
SOCS1 0.037 0.012 -10000 0 0 51 51
EntrezGene:6955 -0.001 0.01 -10000 0 -0.026 59 59
CD3D 0.026 0.03 -10000 0 -0.039 67 67
CD3E 0.028 0.029 -10000 0 -0.038 68 68
CD3G 0.025 0.029 -10000 0 -0.041 57 57
IL12Rbeta2/JAK2 0.029 0.074 -10000 0 -0.13 44 44
CCL3 -0.043 0.32 0.47 1 -0.79 61 62
CCL4 -0.03 0.27 -10000 0 -0.56 84 84
HLA-A 0.038 0.013 -10000 0 -10000 0 0
IL18/IL18R 0.053 0.082 -10000 0 -0.12 73 73
NOS2 -0.026 0.27 0.38 2 -0.54 82 84
IL12/IL12R/TYK2/JAK2/SPHK2 0.027 0.1 0.21 17 -0.23 37 54
IL1R1 -0.11 0.43 -10000 0 -0.97 96 96
IL4 0.02 0.044 0.092 6 -0.058 17 23
JAK2 0.023 0.042 -10000 0 -0.049 88 88
EntrezGene:6957 -0.001 0.009 -10000 0 -0.024 36 36
TCR/CD3/MHC I/CD8 -0.013 0.11 -10000 0 -0.42 26 26
RAB7A -0.031 0.27 0.38 1 -0.57 79 80
lysosomal transport -0.027 0.26 0.37 1 -0.55 79 80
FOS -0.18 0.51 -10000 0 -1.1 124 124
STAT4 (dimer) -0.022 0.29 0.4 5 -0.6 77 82
STAT5A (dimer) -0.02 0.28 -10000 0 -0.57 81 81
GZMA -0.051 0.34 -10000 0 -0.87 58 58
GZMB -0.034 0.3 0.43 1 -0.72 63 64
HLX 0 0 -10000 0 -10000 0 0
LCK -0.039 0.28 0.4 3 -0.59 83 86
TCR/CD3/MHC II/CD4 -0.066 0.2 -10000 0 -0.36 128 128
IL2/IL2R 0.045 0.08 -10000 0 -0.11 90 90
MAPK14 -0.047 0.32 -10000 0 -0.7 78 78
CCR5 -0.02 0.25 0.37 2 -0.5 85 87
IL1B 0.023 0.041 -10000 0 -0.048 88 88
STAT6 0.009 0.14 -10000 0 -0.56 13 13
STAT4 0.039 0.008 -10000 0 0 24 24
STAT3 0.038 0.011 -10000 0 0 41 41
STAT1 0.034 0.016 -10000 0 0 102 102
NFKB1 0.036 0.013 -10000 0 0 66 66
NFKB2 0.04 0.007 -10000 0 0 18 18
IL12B 0.027 0.045 -10000 0 -0.048 114 114
CD8A 0.042 0.005 -10000 0 -10000 0 0
CD8B 0.001 0 -10000 0 -10000 0 0
T-helper 1 cell differentiation 0 0 -10000 0 -10000 0 0
natural killer cell mediated cytotoxicity -0.028 0.1 0.23 33 -0.21 16 49
IL2RB 0.035 0.014 -10000 0 0 76 76
proteasomal ubiquitin-dependent protein catabolic process -0.015 0.27 0.39 5 -0.56 77 82
IL2RG 0.028 0.019 -10000 0 0 179 179
IL12 0.024 0.072 -10000 0 -0.13 44 44
STAT5A 0.038 0.01 -10000 0 0 36 36
CD247 -0.001 0.009 -10000 0 -0.024 38 38
IL2 0.039 0.01 -10000 0 0 34 34
SPHK2 0.04 0.008 -10000 0 0 20 20
FRAP1 0.039 0.009 -10000 0 0 28 28
IL12A 0.02 0.04 -10000 0 -0.049 83 83
IL12/IL12R/TYK2/JAK2 -0.047 0.29 -10000 0 -0.63 80 80
MAP2K3 -0.05 0.33 0.41 1 -0.72 79 80
RIPK2 0.032 0.017 -10000 0 0 119 119
MAP2K6 -0.055 0.31 -10000 0 -0.67 83 83
regulation of dendritic cell antigen processing and presentation 0 0 -10000 0 -10000 0 0
HLA-DRA 0.023 0.029 -10000 0 -0.012 203 203
IL18RAP 0.039 0.019 -10000 0 -0.041 23 23
IL12Rbeta1/TYK2 0.038 0.057 -10000 0 -0.079 21 21
EOMES 0.005 0.072 -10000 0 -0.55 7 7
STAT1 (dimer) -0.043 0.28 0.4 2 -0.58 86 88
T cell proliferation -0.021 0.23 0.35 6 -0.48 80 86
T-helper 1 cell lineage commitment 0 0 -10000 0 -10000 0 0
IL18R1 0.039 0.019 -10000 0 -0.041 22 22
CD8-positive alpha-beta T cell lineage commitment 0 0 -10000 0 -10000 0 0
NF kappa B1 p50/RelA -0.029 0.25 -10000 0 -0.53 76 76
ATF2 -0.046 0.3 -10000 0 -0.65 79 79
Fc-epsilon receptor I signaling in mast cells

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PPAP2A 0.037 0.012 -10000 0 0 53 53
LAT2 -0.019 0.1 0.19 5 -0.22 87 92
AP1 -0.025 0.18 0.28 3 -0.41 66 69
mol:PIP3 -0.031 0.13 0.26 10 -0.31 64 74
IKBKB -0.011 0.09 0.2 25 -0.19 57 82
AKT1 0.02 0.12 0.25 67 -0.21 10 77
IKBKG -0.019 0.084 0.2 8 -0.19 60 68
MS4A2 0.046 0.012 0.07 38 -0.004 10 48
mol:Sphingosine-1-phosphate 0 0 -10000 0 -10000 0 0
PIK3CA 0.029 0.019 -10000 0 0 166 166
MAP3K1 -0.006 0.14 0.24 50 -0.29 61 111
mol:Ca2+ -0.022 0.11 0.22 12 -0.25 58 70
LYN 0.035 0.018 0.078 1 -0.003 92 93
CBLB -0.014 0.095 0.18 7 -0.21 77 84
SHC1 0.039 0.008 -10000 0 0 23 23
RasGAP/p62DOK 0.023 0.071 -10000 0 -0.1 103 103
positive regulation of cell migration -0.01 0.001 -10000 0 -10000 0 0
INPP5D 0 0 -10000 0 -10000 0 0
PLD2 -0.012 0.075 0.29 16 -0.16 4 20
PTPN13 -0.059 0.2 -10000 0 -0.69 33 33
PTPN11 0.039 0.019 0.081 3 -0.033 22 25
GO:0007205 0 0 -10000 0 -10000 0 0
regulation of mast cell degranulation -0.005 0.13 0.28 20 -0.33 30 50
SYK 0.037 0.017 0.078 1 -0.003 74 75
GRB2 0.04 0.008 -10000 0 0 21 21
LAT/PLCgamma1/GRB2/SLP76/GADs -0.024 0.13 0.18 1 -0.27 91 92
LAT -0.017 0.097 0.2 1 -0.21 84 85
PAK2 -0.002 0.15 0.24 58 -0.3 66 124
NFATC2 0.003 0.054 -10000 0 -0.39 9 9
HRAS -0.026 0.14 0.27 3 -0.32 71 74
GAB2 0.031 0.018 -10000 0 0 136 136
PLA2G1B 0.012 0.14 -10000 0 -0.9 12 12
Fc epsilon R1 0.033 0.071 -10000 0 -0.093 111 111
Antigen/IgE/Fc epsilon R1 0.035 0.063 -10000 0 -0.079 102 102
mol:GDP -0.025 0.16 0.23 5 -0.4 58 63
JUN 0.035 0.014 -10000 0 0 76 76
mol:Ca++ 0 0 -10000 0 -10000 0 0
PIK3R1 0.034 0.016 -10000 0 0 99 99
FOS 0.026 0.02 -10000 0 0 201 201
Antigen/IgE/Fc epsilon R1/LYN/SYK -0.011 0.1 0.14 8 -0.22 85 93
CHUK -0.021 0.085 0.19 11 -0.19 66 77
KLRG1 -0.016 0.079 -10000 0 -0.17 84 84
VAV1 -0.013 0.094 0.17 5 -0.22 72 77
calcium-dependent protein kinase C activity 0 0 -10000 0 -10000 0 0
CBL -0.017 0.097 0.18 4 -0.21 82 86
negative regulation of mast cell degranulation -0.021 0.074 -10000 0 -0.19 50 50
BTK -0.033 0.18 -10000 0 -0.48 53 53
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK -0.026 0.1 -10000 0 -0.21 105 105
GAB2/PI3K/SHP2 -0.038 0.053 -10000 0 -0.15 64 64
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP 0 0.058 -10000 0 -0.13 77 77
RAF1 0.015 0.15 -10000 0 -0.99 12 12
Fc epsilon R1/FcgammaRIIB/SHIP 0.032 0.091 -10000 0 -0.12 124 124
FCER1G 0.027 0.02 -10000 0 0 189 189
FCER1A 0.039 0.014 -10000 0 -0.006 41 41
Antigen/IgE/Fc epsilon R1/Fyn 0.04 0.076 -10000 0 -0.09 107 107
MAPK3 0.012 0.14 -10000 0 -0.91 12 12
MAPK1 0.006 0.14 -10000 0 -0.92 12 12
NFKB1 0.036 0.013 -10000 0 0 66 66
MAPK8 -0.035 0.22 -10000 0 -0.58 57 57
DUSP1 0.026 0.02 -10000 0 0 196 196
NF-kappa-B/RelA 0.002 0.069 0.14 16 -0.14 61 77
actin cytoskeleton reorganization -0.052 0.2 -10000 0 -0.73 30 30
mol:Glucocorticoid Dexamethasone 0 0 -10000 0 -10000 0 0
PI3K -0.018 0.13 0.26 5 -0.27 75 80
FER -0.017 0.096 0.2 1 -0.22 78 79
RELA 0.04 0.006 -10000 0 0 10 10
ITK -0.002 0.056 -10000 0 -0.29 15 15
SOS1 0.037 0.012 -10000 0 0 51 51
PLCG1 -0.026 0.15 0.3 4 -0.35 69 73
cytokine secretion -0.002 0.047 0.083 8 -0.098 63 71
SPHK1 -0.016 0.098 0.19 6 -0.21 83 89
PTK2 -0.056 0.21 -10000 0 -0.78 30 30
NTAL/PLCgamma1/GRB2/SLP76/GADs -0.018 0.14 -10000 0 -0.28 90 90
EDG1 -0.01 0.001 -10000 0 -10000 0 0
mol:DAG -0.031 0.14 0.26 10 -0.31 67 77
MAP2K2 0.005 0.14 -10000 0 -0.92 12 12
MAP2K1 0.004 0.14 -10000 0 -0.92 12 12
MAP2K7 0.038 0.011 -10000 0 0 41 41
KLRG1/SHP2 0.011 0.09 0.2 30 -0.18 53 83
MAP2K4 -0.081 0.34 -10000 0 -0.9 78 78
Fc epsilon R1/FcgammaRIIB 0.034 0.098 -10000 0 -0.13 124 124
mol:Choline -0.012 0.074 0.29 16 -0.16 4 20
SHC/Grb2/SOS1 0.023 0.13 0.24 1 -0.21 91 92
FYN 0.034 0.016 -10000 0 0 94 94
DOK1 0.04 0.008 -10000 0 0 22 22
PXN -0.054 0.2 -10000 0 -0.7 30 30
HCLS1 -0.012 0.1 0.18 7 -0.24 62 69
PRKCB -0.023 0.11 0.22 10 -0.24 68 78
FCGR2B 0.03 0.019 -10000 0 0 153 153
IGHE 0 0.006 0.037 1 -10000 0 1
KLRG1/SHIP -0.021 0.075 -10000 0 -0.2 50 50
LCP2 0.034 0.016 -10000 0 0 101 101
PLA2G4A -0.008 0.09 0.15 5 -0.22 63 68
RASA1 0.037 0.013 -10000 0 0 56 56
mol:Phosphatidic acid -0.012 0.074 0.29 16 -0.16 4 20
IKK complex -0.014 0.075 0.19 18 -0.16 46 64
WIPF1 0 0 -10000 0 -10000 0 0
Cellular roles of Anthrax toxin

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
ANTXR1 0.032 0.017 -10000 0 0 116 116
ANTXR2 0.035 0.015 -10000 0 0 87 87
negative regulation of myeloid dendritic cell antigen processing and presentation -0.006 0.011 -10000 0 -0.033 72 72
monocyte activation -0.082 0.17 -10000 0 -0.35 150 150
MAP2K2 -0.041 0.18 -10000 0 -0.58 55 55
MAP2K1 -0.011 0.011 0.008 38 -0.037 68 106
MAP2K7 -0.01 0.011 0.008 36 -0.037 65 101
MAP2K6 -0.009 0.012 0.008 33 -0.039 58 91
CYAA -0.023 0.033 -10000 0 -0.1 72 72
MAP2K4 -0.01 0.012 0.008 32 -0.038 64 96
IL1B -0.01 0.038 0.1 9 -0.084 75 84
Channel 0.022 0.056 -10000 0 -0.11 72 72
NLRP1 -0.006 0.01 -10000 0 -0.031 72 72
CALM1 0.039 0.009 -10000 0 0 26 26
negative regulation of phagocytosis 0.001 0.074 -10000 0 -0.43 15 15
mol:Ca2+ 0 0 -10000 0 -10000 0 0
regulation of endothelial cell proliferation 0.006 0.011 0.033 72 -10000 0 72
MAPK3 -0.011 0.012 0.008 37 -0.037 71 108
MAPK1 -0.01 0.011 0.008 35 -0.037 64 99
PGR -0.008 0.011 0.009 37 -0.037 51 88
PA/Cellular Receptors 0.023 0.062 -10000 0 -0.12 72 72
apoptosis -0.006 0.011 -10000 0 -0.033 72 72
LOC728358 0 0 -10000 0 -10000 0 0
Lethal toxin (unfolded) 0.021 0.056 -10000 0 -0.11 72 72
macrophage activation -0.01 0.03 0.17 10 -0.11 2 12
TNF 0.04 0.008 -10000 0 0 22 22
VCAM1 -0.081 0.17 -10000 0 -0.36 148 148
platelet activation 0.001 0.074 -10000 0 -0.43 15 15
MAPKKK cascade 0.008 0.027 0.083 9 -0.071 19 28
IL18 -0.006 0.038 0.1 10 -0.084 63 73
negative regulation of macrophage activation -0.006 0.011 -10000 0 -0.033 72 72
LEF -0.006 0.011 -10000 0 -0.033 72 72
CASP1 0 0.012 0.019 35 -0.03 48 83
mol:cAMP 0.001 0.074 -10000 0 -0.43 15 15
necrosis -0.006 0.011 -10000 0 -0.033 72 72
intracellular pH reduction 0 0 -10000 0 -10000 0 0
PAGA 0 0 -10000 0 -10000 0 0
Edema toxin (unfolded) 0.023 0.053 -10000 0 -0.1 72 72
mol:Epigallocatechin-3-gallate (EGCG) 0 0 -10000 0 -10000 0 0
Canonical Wnt signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
HDAC1 0.054 0.062 0.15 116 -0.032 30 146
AES 0.052 0.054 0.13 119 -0.032 13 132
FBXW11 0.04 0.008 -10000 0 0 22 22
mol:GTP 0.001 0.003 0.033 1 -10000 0 1
LRP6/FZD1 0.042 0.048 -10000 0 -0.13 32 32
SMAD4 0.038 0.011 -10000 0 0 43 43
DKK2 0.039 0.01 -10000 0 0 33 33
TLE1 0.052 0.051 0.13 114 -0.033 11 125
MACF1 0.033 0.016 -10000 0 0 106 106
CTNNB1 0.029 0.12 0.3 24 -0.42 12 36
WIF1 0.039 0.009 -10000 0 -0.001 27 27
beta catenin/RanBP3 0.092 0.22 0.46 112 -0.39 10 122
KREMEN2 0.039 0.009 -10000 0 0 29 29
DKK1 0.038 0.011 -10000 0 0 39 39
beta catenin/beta TrCP1 0.049 0.12 0.31 24 -0.4 12 36
FZD1 0.04 0.006 -10000 0 0 13 13
AXIN2 -0.051 0.21 0.8 2 -0.81 25 27
AXIN1 0.039 0.011 -10000 0 0 39 39
RAN 0.04 0.009 0.075 1 0 21 22
Axin1/APC/GSK3/beta catenin 0.02 0.14 0.41 1 -0.48 32 33
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4 -0.026 0.17 0.28 8 -0.37 76 84
Axin1/APC/GSK3 0.024 0.079 0.2 13 -0.26 15 28
Axin1/APC/GSK3/beta catenin/Macf1 0.017 0.088 0.28 10 -0.3 14 24
HNF1A 0.018 0.05 0.089 131 -10000 0 131
CTBP1 0.053 0.052 0.13 116 -0.033 11 127
MYC 0.037 0.53 0.64 141 -1.1 67 208
RANBP3 0.039 0.012 0.075 1 0 42 43
DKK2/LRP6/Kremen 2 0.058 0.053 -10000 0 -0.12 29 29
NKD1 0.038 0.011 -10000 0 0 43 43
TCF4 0.054 0.057 0.14 116 -0.032 11 127
TCF3 0.051 0.052 0.13 117 -0.033 12 129
WNT1/LRP6/FZD1/Axin1 0.075 0.061 -10000 0 -0.11 30 30
Ran/GTP 0.03 0.014 0.1 1 -0.12 3 4
CtBP/CBP/TCF/TLE1/AES 0.051 0.3 0.54 110 -0.36 34 144
LEF1 0.036 0.048 0.13 73 -0.032 12 85
DVL1 0.028 0.081 0.23 10 -0.32 13 23
CSNK2A1 0.038 0.012 -10000 0 0 47 47
beta catenin/TCF/CtBP/CBP/TLE1/AES -0.065 0.19 -10000 0 -0.4 91 91
DKK1/LRP6/Kremen 2 0.056 0.053 -10000 0 -0.12 28 28
LRP6 0.034 0.016 -10000 0 0 94 94
CSNK1A1 0.057 0.064 0.15 127 -0.032 33 160
NLK 0.029 0.026 -10000 0 -0.035 68 68
CCND1 -0.18 0.5 0.72 11 -1.2 94 105
WNT1 0.041 0.006 -10000 0 0 10 10
GSK3A 0.038 0.012 0.065 1 0 46 47
GSK3B 0.039 0.008 -10000 0 0 23 23
FRAT1 0.039 0.009 -10000 0 -0.004 19 19
PPP2R5D 0.031 0.071 0.24 2 -0.38 10 12
APC -0.006 0.077 0.2 57 -10000 0 57
WNT1/LRP6/FZD1 0.018 0.064 0.18 3 -0.24 10 13
CREBBP 0.052 0.053 0.13 118 -0.033 14 132
Syndecan-4-mediated signaling events

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
PTK2 -0.064 0.21 -10000 0 -0.35 163 163
Syndecan-4/Syndesmos -0.039 0.19 0.3 2 -0.47 54 56
positive regulation of JNK cascade -0.058 0.19 0.3 1 -0.43 71 72
Syndecan-4/ADAM12 -0.055 0.18 0.3 2 -0.46 58 60
CCL5 0.029 0.019 -10000 0 0 160 160
Rac1/GDP 0.029 0.009 -10000 0 -0.12 1 1
DNM2 0.036 0.014 -10000 0 0 72 72
ITGA5 0.036 0.013 -10000 0 0 64 64
SDCBP 0.035 0.014 -10000 0 0 77 77
PLG 0.033 0.028 -10000 0 -0.042 50 50
ADAM12 0.03 0.018 -10000 0 0 152 152
mol:GTP 0 0 -10000 0 -10000 0 0
NUDT16L1 0.039 0.01 -10000 0 0 33 33
mol:PI-4-5-P2 0 0 -10000 0 -10000 0 0
Syndecan-4/PKC alpha -0.023 0.022 -10000 0 -10000 0 0
Syndecan-4/Laminin alpha1 -0.042 0.18 -10000 0 -0.46 53 53
Syndecan-4/CXCL12/CXCR4 -0.061 0.2 0.31 1 -0.46 70 71
Syndecan-4/Laminin alpha3 -0.049 0.19 0.3 1 -0.47 56 57
MDK 0.039 0.008 -10000 0 0 23 23
Syndecan-4/FZD7 -0.042 0.19 0.3 2 -0.47 56 58
Syndecan-4/Midkine -0.04 0.19 0.3 2 -0.47 55 57
FZD7 0.036 0.013 -10000 0 0 64 64
Syndecan-4/FGFR1/FGF -0.028 0.18 -10000 0 -0.45 48 48
THBS1 0.027 0.02 -10000 0 0 190 190
integrin-mediated signaling pathway -0.056 0.18 0.3 2 -0.42 78 80
positive regulation of MAPKKK cascade -0.058 0.19 0.3 1 -0.43 71 72
Syndecan-4/TACI -0.039 0.19 0.3 2 -0.47 55 57
CXCR4 0.033 0.017 -10000 0 0 115 115
cell adhesion -0.035 0.092 0.21 2 -0.2 120 122
Syndecan-4/Dynamin -0.037 0.18 -10000 0 -0.47 49 49
Syndecan-4/TSP1 -0.059 0.19 0.3 2 -0.46 61 63
Syndecan-4/GIPC -0.037 0.18 -10000 0 -0.48 46 46
Syndecan-4/RANTES -0.051 0.19 0.3 1 -0.47 61 62
ITGB1 0.038 0.01 -10000 0 0 36 36
LAMA1 0.033 0.016 -10000 0 0 104 104
LAMA3 0.03 0.018 -10000 0 0 151 151
RAC1 0.039 0.009 -10000 0 0 28 28
PRKCA 0 0.1 0.9 5 -10000 0 5
Syndecan-4/alpha-Actinin -0.04 0.19 0.3 2 -0.47 56 58
TFPI 0.039 0.01 -10000 0 0 32 32
F2 0.037 0.026 0.087 2 -0.037 49 51
alpha5/beta1 Integrin 0.043 0.046 -10000 0 -0.13 29 29
positive regulation of cell adhesion -0.056 0.17 -10000 0 -0.45 55 55
ACTN1 0.039 0.01 -10000 0 0 32 32
TNC 0.027 0.02 -10000 0 0 189 189
Syndecan-4/CXCL12 -0.058 0.19 0.3 2 -0.46 65 67
FGF6 0.037 0.012 -10000 0 0 55 55
RHOA 0.04 0.006 -10000 0 0 13 13
CXCL12 0.028 0.019 -10000 0 0 174 174
TNFRSF13B 0.037 0.012 -10000 0 0 50 50
FGF2 0.039 0.01 -10000 0 0 33 33
FGFR1 0.033 0.017 -10000 0 0 112 112
Syndecan-4/PI-4-5-P2 -0.062 0.17 -10000 0 -0.46 56 56
mol:GDP 0 0 -10000 0 -10000 0 0
FN1 0.017 0.024 -10000 0 -0.04 24 24
cell migration -0.011 0.013 -10000 0 -10000 0 0
PRKCD 0.033 0.027 -10000 0 -0.042 44 44
vasculogenesis -0.056 0.18 0.3 2 -0.44 62 64
SDC4 -0.055 0.18 -10000 0 -0.5 50 50
Syndecan-4/Tenascin C -0.059 0.19 0.3 2 -0.46 65 67
Syndecan-4/PI-4-5-P2/PKC alpha -0.019 0.017 -10000 0 -10000 0 0
Syndecan-4/Syntenin -0.041 0.19 0.3 2 -0.48 52 54
MMP9 0.027 0.023 -10000 0 -0.038 18 18
Rac1/GTP -0.036 0.094 0.21 2 -0.2 120 122
cytoskeleton organization -0.037 0.18 0.3 2 -0.4 73 75
GIPC1 0.034 0.015 -10000 0 0 92 92
Syndecan-4/TFPI -0.04 0.19 0.3 2 -0.46 57 59
Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin 0.006 0.051 -10000 0 -0.15 42 42
EPHB2 0.038 0.01 -10000 0 0 38 38
Syndecan-2/TACI 0.024 0.041 -10000 0 -0.1 39 39
LAMA1 0.033 0.016 -10000 0 0 104 104
Syndecan-2/alpha2 ITGB1 0.034 0.088 0.19 40 -0.12 88 128
HRAS 0.039 0.01 -10000 0 0 31 31
Syndecan-2/CASK 0 0.028 -10000 0 -0.097 42 42
ITGA5 0.036 0.013 -10000 0 0 64 64
BAX 0.023 0.068 -10000 0 -10000 0 0
EPB41 0.039 0.01 -10000 0 0 31 31
positive regulation of cell-cell adhesion 0.016 0.045 -10000 0 -0.096 67 67
LAMA3 0.03 0.018 -10000 0 0 151 151
EZR 0 0 -10000 0 -10000 0 0
mol:PI-4-5-P2 0 0 -10000 0 -10000 0 0
CAV2 0.033 0.016 -10000 0 0 105 105
Syndecan-2/MMP2 0.007 0.053 -10000 0 -0.16 42 42
RP11-540L11.1 0 0 -10000 0 -10000 0 0
alpha2 ITGB1 0.034 0.057 -10000 0 -0.14 46 46
dendrite morphogenesis 0.024 0.043 -10000 0 -0.11 39 39
Syndecan-2/GM-CSF 0.025 0.041 -10000 0 -0.1 41 41
determination of left/right symmetry 0.01 0.007 -10000 0 -10000 0 0
Syndecan-2/PKC delta 0.023 0.041 -10000 0 -0.11 40 40
GNB2L1 0.039 0.009 -10000 0 0 30 30
MAPK3 0.012 0.077 0.15 108 -0.099 39 147
MAPK1 0.011 0.076 0.15 104 -0.099 38 142
Syndecan-2/RACK1 0.038 0.047 -10000 0 -0.091 44 44
NF1 0.034 0.016 -10000 0 0 96 96
FGFR/FGF/Syndecan-2 0.01 0.007 -10000 0 -10000 0 0
ITGA2 0.033 0.017 -10000 0 0 114 114
MAPK8 -0.004 0.005 -10000 0 -10000 0 0
Syndecan-2/alpha2/beta1 Integrin 0.048 0.08 0.19 50 -0.11 57 107
Syndecan-2/Kininogen 0.022 0.039 -10000 0 -0.1 36 36
ITGB1 0.038 0.01 -10000 0 0 36 36
SRC 0.008 0.076 0.19 66 -10000 0 66
Syndecan-2/CASK/Protein 4.1 0.022 0.037 -10000 0 -0.092 43 43
extracellular matrix organization 0.022 0.042 -10000 0 -0.11 39 39
actin cytoskeleton reorganization 0.006 0.051 -10000 0 -0.15 42 42
Syndecan-2/Caveolin-2/Ras 0.028 0.059 -10000 0 -0.11 64 64
Syndecan-2/Laminin alpha3 0.017 0.046 -10000 0 -0.13 35 35
Syndecan-2/RasGAP 0.062 0.068 0.18 52 -0.092 56 108
alpha5/beta1 Integrin 0.043 0.046 -10000 0 -0.13 29 29
PRKCD 0.037 0.012 -10000 0 0 51 51
Syndecan-2 dimer 0.024 0.043 -10000 0 -0.11 39 39
GO:0007205 0.003 0.001 -10000 0 -10000 0 0
DNA mediated transformation 0 0 -10000 0 -10000 0 0
Syndecan-2/RasGAP/Src 0.039 0.059 0.2 3 -0.097 49 52
RHOA 0.04 0.006 -10000 0 0 13 13
SDCBP 0.035 0.014 -10000 0 0 77 77
TNFRSF13B 0.037 0.012 -10000 0 0 50 50
RASA1 0.037 0.013 -10000 0 0 56 56
alpha2/beta1 Integrin 0.034 0.057 -10000 0 -0.14 46 46
Syndecan-2/Synbindin 0.019 0.044 -10000 0 -0.11 41 41
TGFB1 0.036 0.014 -10000 0 0 69 69
CASP3 0.008 0.075 0.15 94 -0.1 49 143
FN1 0.021 0.021 -10000 0 0 268 268
Syndecan-2/IL8 0.018 0.044 -10000 0 -0.12 39 39
SDC2 0.01 0.007 -10000 0 -10000 0 0
KNG1 0.034 0.016 -10000 0 0 100 100
Syndecan-2/Neurofibromin 0.021 0.042 -10000 0 -0.11 37 37
TRAPPC4 0.034 0.016 -10000 0 0 97 97
CSF2 0.04 0.008 -10000 0 0 21 21
Syndecan-2/TGFB1 0.022 0.042 -10000 0 -0.11 39 39
Syndecan-2/Syntenin/PI-4-5-P2 0.016 0.045 -10000 0 -0.096 67 67
Syndecan-2/Ezrin 0.023 0.038 -10000 0 -0.093 45 45
PRKACA 0.004 0.071 0.15 80 -0.1 53 133
angiogenesis 0.018 0.044 -10000 0 -0.12 39 39
MMP2 0.021 0.021 -10000 0 0 265 265
IL8 0.031 0.018 -10000 0 0 129 129
calcineurin-NFAT signaling pathway 0.024 0.04 -10000 0 -0.1 39 39
IL6-mediated signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BCL2L1 -0.081 0.35 0.49 2 -0.79 81 83
CRP -0.08 0.33 0.5 1 -0.78 74 75
cell cycle arrest -0.12 0.39 -10000 0 -0.87 91 91
TIMP1 -0.1 0.36 -10000 0 -0.76 107 107
IL6ST 0.025 0.036 -10000 0 -0.043 65 65
Rac1/GDP -0.008 0.17 0.29 7 -0.38 58 65
AP1 -0.027 0.21 -10000 0 -0.48 65 65
GAB2 0.032 0.02 -10000 0 -0.045 2 2
TNFSF11 -0.084 0.33 -10000 0 -0.77 77 77
HSP90B1 0.011 0.093 -10000 0 -1.1 2 2
GAB1 0.038 0.014 -10000 0 -0.04 2 2
MAPK14 -0.029 0.17 -10000 0 -0.62 30 30
AKT1 -0.004 0.15 0.28 3 -0.45 31 34
FOXO1 -0.005 0.14 0.26 3 -0.44 30 33
MAP2K6 -0.021 0.15 0.22 1 -0.42 48 49
mol:GTP 0 0.003 -10000 0 -10000 0 0
MAP2K4 -0.034 0.2 0.31 9 -0.43 79 88
MITF -0.016 0.15 0.23 5 -0.35 58 63
positive regulation of NF-kappaB transcription factor activity 0 0 -10000 0 -10000 0 0
TYK2 0.036 0.013 -10000 0 0 65 65
A2M -0.12 0.41 -10000 0 -1.2 66 66
CEBPB 0.036 0.014 -10000 0 0 72 72
GRB2/SOS1/GAB family/SHP2 -0.009 0.16 0.31 3 -0.4 56 59
STAT3 -0.14 0.42 -10000 0 -0.96 91 91
STAT1 -0.071 0.28 -10000 0 -0.83 64 64
CEBPD -0.083 0.34 0.52 2 -0.79 75 77
PIK3CA 0.029 0.02 -10000 0 -0.047 2 2
PI3K 0.023 0.06 -10000 0 -0.15 46 46
JUN 0.036 0.014 -10000 0 0 76 76
PIAS3/MITF -0.004 0.15 -10000 0 -0.34 53 53
MAPK11 -0.026 0.16 -10000 0 -0.6 30 30
STAT3 (dimer)/FOXO1 -0.089 0.36 0.41 2 -0.74 98 100
GRB2/SOS1/GAB family 0.03 0.13 0.3 4 -0.29 31 35
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK 0.001 0.11 0.19 3 -0.27 54 57
GRB2 0.041 0.01 -10000 0 -0.002 22 22
JAK2 0.034 0.016 -10000 0 0 101 101
LBP -0.031 0.26 0.47 1 -0.57 71 72
PIK3R1 0.034 0.017 -10000 0 -0.001 102 102
JAK1 0.032 0.029 -10000 0 -0.043 58 58
MYC -0.071 0.42 0.5 8 -0.87 97 105
FGG -0.083 0.33 -10000 0 -0.76 78 78
macrophage differentiation -0.12 0.39 -10000 0 -0.87 91 91
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4 0.049 0.1 -10000 0 -0.18 48 48
JUNB -0.097 0.39 0.5 7 -0.86 94 101
FOS 0.026 0.02 -10000 0 0 201 201
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 -0.01 0.16 0.22 5 -0.36 63 68
STAT1/PIAS1 -0.015 0.18 0.28 2 -0.36 76 78
GRB2/SOS1/GAB family/SHP2/PI3K -0.008 0.15 -10000 0 -0.41 43 43
STAT3 (dimer) -0.14 0.41 -10000 0 -0.93 91 91
PRKCD -0.058 0.26 0.34 10 -0.53 93 103
IL6R 0.032 0.028 -10000 0 -0.043 47 47
SOCS3 -0.042 0.22 -10000 0 -1 22 22
gp130 (dimer)/JAK1/JAK1/LMO4 0.042 0.088 -10000 0 -0.15 54 54
Rac1/GTP -0.013 0.19 0.3 7 -0.39 68 75
HCK 0.037 0.014 -10000 0 0 65 65
MAPKKK cascade -0.022 0.22 -10000 0 -0.51 67 67
bone resorption -0.077 0.31 -10000 0 -0.72 78 78
IRF1 -0.14 0.42 -10000 0 -0.94 106 106
mol:GDP -0.022 0.15 0.22 4 -0.37 58 62
SOS1 0.039 0.015 -10000 0 -0.001 53 53
VAV1 -0.022 0.15 0.22 4 -0.38 58 62
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3 -0.015 0.18 -10000 0 -0.51 48 48
PTPN11 0.001 0.16 -10000 0 -0.79 21 21
IL6/IL6RA 0.03 0.061 -10000 0 -0.13 41 41
gp130 (dimer)/TYK2/TYK2/LMO4 0.048 0.066 -10000 0 -0.11 46 46
gp130 (dimer)/JAK2/JAK2/LMO4 0.039 0.077 -10000 0 -0.13 60 60
IL6 0.023 0.036 -10000 0 -0.044 69 69
PIAS3 0.038 0.012 -10000 0 0 47 47
PTPRE 0.027 0.037 0.097 13 -0.043 66 79
PIAS1 0.039 0.008 -10000 0 0 24 24
RAC1 0.039 0.009 -10000 0 0 28 28
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4 0.001 0.091 0.16 3 -0.23 43 46
LMO4 0.028 0.037 -10000 0 -0.044 68 68
STAT3 (dimer)/PIAS3 -0.099 0.39 -10000 0 -0.86 89 89
MCL1 0.004 0.16 -10000 0 -0.79 10 10
E-cadherin signaling in keratinocytes

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
keratinocyte differentiation 0 0.11 0.15 67 -0.3 34 101
adherens junction organization -0.017 0.12 0.19 8 -0.35 45 53
mol:GTP 0 0 -10000 0 -10000 0 0
Rac1/GDP 0.02 0.11 0.22 17 -0.28 27 44
FMN1 -0.012 0.11 0.15 9 -0.28 55 64
mol:IP3 0.009 0.096 0.16 69 -0.24 37 106
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin -0.003 0.12 0.16 9 -0.29 59 68
CTNNB1 0.04 0.011 0.068 3 0 32 35
AKT1 -0.012 0.086 0.21 5 -0.27 35 40
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin -0.002 0.14 -10000 0 -0.42 35 35
CTNND1 0.042 0.009 -10000 0 -0.002 18 18
mol:PI-4-5-P2 -0.005 0.12 0.22 21 -0.32 38 59
VASP -0.013 0.11 0.16 5 -0.29 54 59
ZYX -0.01 0.11 0.15 10 -0.3 44 54
JUB -0.015 0.12 0.15 8 -0.29 57 65
EGFR(dimer) 0.004 0.13 -10000 0 -0.32 46 46
E-cadherin/beta catenin-gamma catenin 0.052 0.058 -10000 0 -0.11 45 45
mol:PI-3-4-5-P3 0.001 0.098 -10000 0 -0.27 37 37
PIK3CA 0.029 0.02 -10000 0 -0.001 169 169
PI3K 0.001 0.1 -10000 0 -0.28 37 37
FYN -0.004 0.12 0.19 17 -0.28 58 75
mol:Ca2+ 0.009 0.095 0.16 69 -0.23 37 106
JUP 0.038 0.013 0.068 1 0 57 58
PIK3R1 0.035 0.017 -10000 0 0 100 100
mol:DAG 0.009 0.096 0.16 69 -0.24 37 106
CDH1 0.036 0.015 -10000 0 0 79 79
RhoA/GDP 0.021 0.11 0.22 17 -0.28 28 45
establishment of polarity of embryonic epithelium -0.011 0.11 0.18 8 -0.28 54 62
SRC 0.039 0.009 -10000 0 0 28 28
RAC1 0.039 0.009 -10000 0 0 28 28
RHOA 0.04 0.006 -10000 0 0 13 13
EGFR 0.036 0.014 -10000 0 0 67 67
CASR 0.003 0.094 0.16 76 -0.27 26 102
RhoA/GTP 0.023 0.1 0.2 11 -0.26 27 38
AKT2 -0.013 0.085 0.22 2 -0.27 34 36
actin cable formation -0.016 0.11 0.24 8 -0.32 41 49
apoptosis -0.007 0.11 0.28 37 -0.17 75 112
CTNNA1 0.04 0.011 -10000 0 -0.001 32 32
mol:GDP 0.002 0.1 0.17 72 -0.25 38 110
PIP5K1A -0.013 0.11 0.15 5 -0.29 49 54
PLCG1 0.008 0.098 0.16 69 -0.24 37 106
Rac1/GTP 0.014 0.13 -10000 0 -0.31 43 43
homophilic cell adhesion 0.001 0.005 -10000 0 -10000 0 0
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
MET/RANBP9 0.011 0.075 -10000 0 -0.14 101 101
CRKL -0.024 0.13 0.28 3 -0.42 33 36
mol:PIP3 0.003 0.11 0.3 1 -0.83 8 9
AKT1 -0.003 0.1 0.37 2 -0.74 8 10
PTK2B 0.034 0.016 -10000 0 0 97 97
RAPGEF1 -0.028 0.13 0.26 3 -0.41 32 35
RANBP10 0.037 0.013 -10000 0 0 58 58
PIK3CA 0.029 0.019 -10000 0 0 166 166
HGF/MET/SHIP2 0.028 0.076 -10000 0 -0.12 100 100
MAP3K5 -0.014 0.13 0.27 1 -0.4 30 31
HGF/MET/CIN85/CBL/ENDOPHILINS 0.049 0.083 -10000 0 -0.11 101 101
AP1 -0.004 0.081 0.16 11 -0.14 102 113
mol:SU11274 0 0 -10000 0 -10000 0 0
SHC1 0.039 0.008 -10000 0 0 23 23
apoptosis -0.16 0.35 -10000 0 -0.76 130 130
STAT3 (dimer) -0.006 0.11 0.19 5 -0.29 34 39
GAB1/CRKL/SHP2/PI3K -0.006 0.14 -10000 0 -0.38 37 37
INPP5D 0 0 -10000 0 -10000 0 0
CBL/CRK -0.004 0.14 0.29 2 -0.4 33 35
PTPN11 0.039 0.009 -10000 0 0 29 29
GO:0007205 0 0 -10000 0 -10000 0 0
PLCG1 0.038 0.011 -10000 0 0 43 43
PTEN 0.038 0.01 -10000 0 0 36 36
ELK1 0.011 0.12 0.35 36 -10000 0 36
mol:SU5416 0 0 -10000 0 -10000 0 0
SHP2/GRB2/SOS1GAB1 -0.011 0.081 0.16 1 -0.23 37 38
PAK1 0.004 0.11 0.33 6 -0.68 8 14
HGF/MET/RANBP10 0.025 0.075 -10000 0 -0.11 101 101
HRAS -0.072 0.21 -10000 0 -0.48 114 114
DOCK1 -0.029 0.13 0.25 7 -0.39 36 43
GAB1 -0.023 0.14 -10000 0 -0.44 33 33
CRK -0.022 0.13 0.29 2 -0.42 32 34
mol:PHA665752 0 0 -10000 0 -10000 0 0
mol:GDP -0.054 0.19 -10000 0 -0.42 105 105
JUN 0.035 0.014 -10000 0 0 76 76
EntrezGene:200958 0 0 -10000 0 -10000 0 0
HGF/MET -0.019 0.07 0.094 4 -0.16 100 104
PIK3R1 0.034 0.016 -10000 0 0 99 99
cell morphogenesis 0 0.15 0.27 35 -0.34 34 69
GRB2/SHC 0.018 0.094 -10000 0 -0.16 103 103
FOS 0.026 0.02 -10000 0 0 201 201
GLMN 0.005 0.006 0.068 5 -10000 0 5
cell motility 0.011 0.12 0.35 36 -10000 0 36
HGF/MET/MUC20 0.015 0.062 -10000 0 -0.11 102 102
cell migration 0.017 0.093 -10000 0 -0.16 103 103
GRB2 0.04 0.008 -10000 0 0 21 21
CBL 0.04 0.008 -10000 0 0 20 20
MET/RANBP10 0.011 0.073 -10000 0 -0.13 102 102
HGF/MET/Paxillin/FAK1/FAK12/RasGAP -0.015 0.08 -10000 0 -0.18 79 79
MET/MUC20 -0.004 0.06 -10000 0 -0.12 104 104
RAP1B -0.028 0.12 0.33 2 -0.38 29 31
RAP1A -0.032 0.12 0.34 2 -0.39 33 35
HGF/MET/RANBP9 0.027 0.077 -10000 0 -0.12 99 99
RAF1 -0.07 0.21 -10000 0 -0.46 114 114
STAT3 -0.007 0.1 -10000 0 -0.29 33 33
cell proliferation -0.03 0.14 0.26 10 -0.3 75 85
RPS6KB1 -0.01 0.082 -10000 0 -0.26 37 37
MAPK3 -0.008 0.12 0.62 12 -10000 0 12
MAPK1 0.021 0.18 0.71 31 -10000 0 31
RANBP9 0.038 0.012 -10000 0 0 47 47
MAPK8 -0.011 0.14 -10000 0 -0.4 38 38
SRC -0.004 0.093 0.2 10 -0.27 26 36
PI3K 0.002 0.092 -10000 0 -0.18 87 87
MET/Glomulin 0.011 0.047 -10000 0 -0.12 45 45
SOS1 0.037 0.012 -10000 0 0 51 51
MAP2K1 -0.071 0.19 -10000 0 -0.43 114 114
MET 0.027 0.02 -10000 0 0 191 191
MAP4K1 -0.011 0.13 0.27 2 -0.44 28 30
PTK2 0.027 0.019 -10000 0 0 182 182
MAP2K2 -0.07 0.19 -10000 0 -0.42 115 115
BAD -0.008 0.1 0.33 2 -0.71 8 10
MAP2K4 -0.016 0.12 0.26 1 -0.37 30 31
SHP2/GRB2/SOS1/GAB1 -0.009 0.15 -10000 0 -0.35 46 46
INPPL1 0.039 0.009 -10000 0 0 27 27
PXN 0.04 0.006 -10000 0 0 10 10
SH3KBP1 0.04 0.007 -10000 0 0 16 16
HGS -0.026 0.071 0.082 4 -0.16 109 113
PLCgamma1/PKC 0.026 0.02 -10000 0 -0.12 8 8
HGF 0.039 0.009 -10000 0 0 27 27
RASA1 0.037 0.013 -10000 0 0 56 56
NCK1 0.036 0.014 -10000 0 0 70 70
PTPRJ 0.039 0.01 -10000 0 0 33 33
NCK/PLCgamma1 0.014 0.097 -10000 0 -0.17 100 100
PDPK1 -0.004 0.1 -10000 0 -0.77 8 8
HGF/MET/SHIP 0.015 0.062 -10000 0 -0.11 102 102
IL4-mediated signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BCL2L1 -0.059 0.5 0.76 1 -1 69 70
STAT6 (cleaved dimer) -0.1 0.45 -10000 0 -0.95 82 82
IGHG1 0.034 0.23 0.45 3 -0.72 7 10
IGHG3 -0.067 0.45 -10000 0 -0.94 75 75
AKT1 -0.055 0.37 -10000 0 -0.83 67 67
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1 -0.046 0.36 0.44 1 -0.86 67 68
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1 -0.051 0.4 -10000 0 -0.94 64 64
THY1 -0.22 0.66 -10000 0 -1.2 158 158
MYB 0.034 0.016 -10000 0 0 96 96
HMGA1 0.036 0.013 -10000 0 0 65 65
IL4/IL4R/JAK1/IL2R gamma/JAK3 -0.023 0.38 0.52 1 -0.76 66 67
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP -0.055 0.4 -10000 0 -0.9 69 69
SP1 0.021 0.073 -10000 0 -0.12 102 102
INPP5D 0 0 -10000 0 -10000 0 0
SOCS5 0.001 0.05 -10000 0 -0.084 4 4
STAT6 (dimer)/ETS1 -0.082 0.46 -10000 0 -0.97 76 76
SOCS1 -0.026 0.34 -10000 0 -0.67 63 63
SOCS3 -0.038 0.37 0.58 2 -0.98 41 43
FCER2 -0.033 0.39 -10000 0 -0.82 51 51
PARP14 0.033 0.018 -10000 0 0 128 128
CCL17 -0.061 0.47 -10000 0 -1 62 62
GRB2 0.04 0.008 -10000 0 0 21 21
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP -0.011 0.3 -10000 0 -0.65 59 59
T cell proliferation -0.085 0.49 -10000 0 -1 80 80
IL4R/JAK1 -0.076 0.49 -10000 0 -1 77 77
EGR2 -0.057 0.48 -10000 0 -1 61 61
JAK2 0.031 0.071 0.18 2 -10000 0 2
JAK3 0.032 0.026 -10000 0 -0.041 32 32
PIK3R1 0.034 0.016 -10000 0 0 99 99
JAK1 0.04 0.041 0.11 3 -0.04 7 10
COL1A2 -0.16 0.57 -10000 0 -1.3 107 107
CCL26 -0.07 0.49 -10000 0 -1 71 71
IL4R -0.066 0.52 -10000 0 -1.1 75 75
PTPN6 0.005 0.043 -10000 0 -0.08 2 2
IL13RA2 -0.059 0.47 -10000 0 -0.99 70 70
IL13RA1 0.035 0.074 0.18 6 -10000 0 6
IRF4 0.049 0.17 -10000 0 -0.92 5 5
ARG1 0.047 0.2 -10000 0 -0.78 4 4
CBL -0.026 0.35 -10000 0 -0.71 66 66
GTF3A 0.013 0.079 -10000 0 -0.13 120 120
PIK3CA 0.029 0.019 -10000 0 0 166 166
IL13RA1/JAK2 0.039 0.12 0.25 4 -0.18 27 31
IRF4/BCL6 0.034 0.16 -10000 0 -0.87 5 5
CD40LG 0.048 0.008 -10000 0 -0.054 1 1
MAPK14 -0.032 0.37 0.62 1 -0.78 62 63
mitosis -0.046 0.35 -10000 0 -0.77 67 67
STAT6 -0.063 0.54 0.76 2 -1.1 75 77
SPI1 0.044 0.01 -10000 0 -10000 0 0
RPS6KB1 -0.048 0.34 -10000 0 -0.74 67 67
STAT6 (dimer) -0.06 0.54 0.76 2 -1.1 75 77
STAT6 (dimer)/PARP14 -0.1 0.49 -10000 0 -1 76 76
mast cell activation -0.005 0.019 -10000 0 -0.044 9 9
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2 -0.074 0.39 -10000 0 -0.88 72 72
FRAP1 -0.055 0.37 -10000 0 -0.83 67 67
LTA -0.06 0.47 -10000 0 -1 67 67
FES 0.04 0.008 -10000 0 0 22 22
T-helper 1 cell differentiation 0.055 0.53 1.1 75 -0.76 2 77
CCL11 -0.091 0.5 -10000 0 -1 84 84
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES -0.049 0.39 -10000 0 -0.89 65 65
IL2RG 0.026 0.025 -10000 0 -0.047 12 12
IL10 -0.06 0.48 -10000 0 -1 63 63
IRS1 0.04 0.008 -10000 0 0 22 22
IRS2 0.039 0.009 -10000 0 0 30 30
IL4 0.042 0.22 -10000 0 -0.92 12 12
IL5 -0.061 0.47 -10000 0 -1.1 55 55
IL4/IL4R/JAK1/IL13RA1/JAK2 -0.044 0.46 0.68 2 -0.9 78 80
COL1A1 -0.21 0.64 -10000 0 -1.3 136 136
positive regulation of NF-kappaB transcription factor activity 0 0 -10000 0 -10000 0 0
IL4/IL4R/JAK1 -0.082 0.49 -10000 0 -1.1 68 68
IL2R gamma/JAK3 0.02 0.073 -10000 0 -0.13 87 87
TFF3 -0.067 0.49 -10000 0 -1 70 70
ALOX15 -0.058 0.47 -10000 0 -1 67 67
MYBL1 0.036 0.014 -10000 0 0 70 70
T-helper 2 cell differentiation -0.099 0.47 -10000 0 -0.95 86 86
SHC1 0.039 0.008 -10000 0 0 23 23
CEBPB 0.04 0.016 -10000 0 -10000 0 0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2 -0.052 0.4 -10000 0 -0.89 69 69
mol:PI-3-4-5-P3 -0.054 0.37 -10000 0 -0.83 67 67
PI3K -0.065 0.4 -10000 0 -0.91 67 67
DOK2 0.032 0.017 -10000 0 0 118 118
ETS1 0 0.046 -10000 0 -0.1 2 2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2 -0.008 0.29 0.42 1 -0.63 60 61
ITGB3 -0.093 0.54 -10000 0 -1.1 83 83
PIGR -0.057 0.49 -10000 0 -1.1 63 63
IGHE -0.005 0.087 0.18 41 -0.19 23 64
MAPKKK cascade -0.006 0.29 0.42 1 -0.62 60 61
BCL6 0.031 0.017 -10000 0 0 130 130
OPRM1 -0.062 0.47 -10000 0 -1 68 68
RETNLB -0.055 0.48 -10000 0 -1 67 67
SELP -0.057 0.48 -10000 0 -1 62 62
AICDA -0.051 0.45 -10000 0 -0.96 65 65
IL2 signaling events mediated by STAT5

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
GAB2 0.031 0.018 -10000 0 0 137 137
ELF1 0.047 0.023 -10000 0 -0.26 2 2
CCNA2 0.032 0.017 -10000 0 0 122 122
PIK3CA 0.029 0.019 -10000 0 0 166 166
JAK3 0.037 0.013 -10000 0 -0.001 58 58
PIK3R1 0.034 0.016 -10000 0 0 100 100
JAK1 0.039 0.01 -10000 0 -0.001 34 34
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K 0 0.13 0.25 1 -0.34 37 38
SHC1 0.04 0.009 -10000 0 -0.001 24 24
SP1 0.042 0.042 -10000 0 -0.27 9 9
IL2RA 0.02 0.032 -10000 0 -0.49 2 2
IL2RB 0.036 0.015 -10000 0 0 77 77
SOS1 0.038 0.013 -10000 0 -0.001 53 53
IL2RG 0.028 0.02 -10000 0 0 180 180
G1/S transition of mitotic cell cycle -0.036 0.18 0.27 5 -0.47 37 42
PTPN11 0.039 0.011 -10000 0 -0.003 32 32
CCND2 0.011 0.062 -10000 0 -0.49 8 8
LCK 0.039 0.01 -10000 0 -0.003 28 28
GRB2 0.04 0.009 -10000 0 -0.003 23 23
IL2 0.039 0.011 -10000 0 -0.002 36 36
CDK6 0.032 0.017 -10000 0 0 126 126
CCND3 0.004 0.14 0.39 1 -0.6 9 10
a4b1 and a4b7 Integrin signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
ITGB1 0.038 0.01 -9999 0 0 36 36
ITGB7 0.038 0.01 -9999 0 0 38 38
ITGA4 0.035 0.015 -9999 0 0 88 88
alpha4/beta7 Integrin 0.031 0.065 -9999 0 -0.14 66 66
alpha4/beta1 Integrin 0.031 0.065 -9999 0 -0.14 66 66
FoxO family signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
G6PC -0.004 0.063 -10000 0 -10000 0 0
PLK1 -0.15 0.38 -10000 0 -0.95 72 72
CDKN1B -0.041 0.2 0.43 2 -0.37 93 95
FOXO3 -0.13 0.35 -10000 0 -0.68 114 114
KAT2B -0.008 0.028 0.041 2 -0.046 171 173
FOXO1/SIRT1 0.015 0.078 0.2 1 -0.22 19 20
CAT -0.15 0.4 0.52 1 -0.97 78 79
CTNNB1 0.039 0.01 -10000 0 0 32 32
AKT1 0.013 0.055 -10000 0 -0.064 144 144
FOXO1 -0.004 0.071 0.21 2 -0.23 16 18
MAPK10 -0.001 0.045 0.19 4 -0.12 22 26
mol:GTP 0 0.003 -10000 0 -10000 0 0
FOXO4 -0.026 0.12 -10000 0 -0.3 59 59
response to oxidative stress -0.006 0.029 -10000 0 -0.051 105 105
FOXO3A/SIRT1 -0.12 0.34 -10000 0 -0.55 170 170
XPO1 0.039 0.01 -10000 0 0 35 35
EP300 0.037 0.014 -10000 0 -10000 0 0
BCL2L11 0.011 0.11 -10000 0 -0.91 6 6
FOXO1/SKP2 0.011 0.076 -10000 0 -0.22 25 25
mol:GDP -0.006 0.029 -10000 0 -0.051 105 105
RAN 0.04 0.008 -10000 0 0 21 21
GADD45A -0.073 0.27 -10000 0 -0.78 51 51
YWHAQ 0.04 0.007 -10000 0 0 18 18
FOXO1/14-3-3 family 0.008 0.15 -10000 0 -0.4 41 41
MST1 0.011 0.055 -10000 0 -0.063 183 183
CSNK1D 0.039 0.008 -10000 0 0 24 24
CSNK1E 0.037 0.012 -10000 0 0 53 53
FOXO4/14-3-3 family -0.002 0.15 -10000 0 -0.44 39 39
YWHAB 0.038 0.011 -10000 0 0 45 45
MAPK8 -0.001 0.047 0.19 5 -0.12 21 26
MAPK9 -0.003 0.048 0.19 5 -0.13 23 28
YWHAG 0.039 0.009 -10000 0 0 25 25
YWHAE 0.037 0.013 -10000 0 0 58 58
YWHAZ 0.034 0.016 -10000 0 0 96 96
SIRT1 0.037 0.018 0.11 2 -0.035 24 26
SOD2 -0.11 0.3 -10000 0 -0.66 94 94
RBL2 -0.12 0.33 -10000 0 -0.77 78 78
RAL/GDP 0.03 0.056 -10000 0 -0.1 41 41
CHUK 0.012 0.053 -10000 0 -0.063 165 165
Ran/GTP 0.026 0.019 -10000 0 -0.12 3 3
CSNK1G2 0.036 0.013 -10000 0 0 64 64
RAL/GTP 0.031 0.056 -10000 0 -0.092 48 48
CSNK1G1 0.04 0.007 -10000 0 0 16 16
FASLG 0.017 0.066 -10000 0 -1.2 1 1
SKP2 0.036 0.014 -10000 0 0 68 68
USP7 0.038 0.012 -10000 0 0 47 47
IKBKB 0.011 0.054 -10000 0 -0.062 171 171
CCNB1 -0.18 0.43 -10000 0 -1 92 92
FOXO1-3a-4/beta catenin -0.057 0.2 -10000 0 -0.4 90 90
proteasomal ubiquitin-dependent protein catabolic process 0.011 0.075 -10000 0 -0.22 25 25
CSNK1A1 0.039 0.008 -10000 0 0 23 23
SGK1 -0.008 0.028 0.041 2 -0.046 171 173
CSNK1G3 0.039 0.01 -10000 0 0 31 31
Ran/GTP/Exportin 1 0.044 0.038 -10000 0 -0.1 27 27
ZFAND5 -0.02 0.1 -10000 0 -0.25 58 58
SFN 0.035 0.015 -10000 0 0 83 83
CDK2 0.039 0.013 -10000 0 -10000 0 0
FOXO3A/14-3-3 -0.01 0.16 -10000 0 -0.37 58 58
CREBBP 0.04 0.013 -10000 0 -10000 0 0
FBXO32 -0.2 0.54 -10000 0 -1.1 132 132
BCL6 -0.12 0.34 -10000 0 -0.94 58 58
RALB 0.039 0.009 -10000 0 0 25 25
RALA 0.04 0.008 -10000 0 0 19 19
YWHAH 0.038 0.011 -10000 0 0 46 46
Noncanonical Wnt signaling pathway

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
NFATC2 0.036 0.014 -10000 0 0 68 68
GNB1/GNG2 0.01 0.12 -10000 0 -0.26 45 45
mol:DAG -0.009 0.1 0.24 7 -0.25 42 49
PLCG1 -0.01 0.1 0.22 6 -0.25 43 49
YES1 -0.019 0.093 -10000 0 -0.26 43 43
FZD3 0.03 0.019 -10000 0 0 153 153
FZD6 0.029 0.019 -10000 0 0 162 162
G protein 0.021 0.12 0.24 30 -0.26 40 70
MAP3K7 -0.03 0.084 0.2 6 -0.22 43 49
mol:Ca2+ -0.009 0.1 0.24 7 -0.24 42 49
mol:IP3 -0.009 0.1 0.24 7 -0.25 42 49
NLK -0.036 0.26 -10000 0 -0.82 54 54
GNB1 0.039 0.01 -10000 0 0 33 33
CAMK2A -0.019 0.092 0.22 7 -0.24 41 48
MAP3K7IP1 0.037 0.012 -10000 0 0 51 51
Noncanonical Wnts/FZD -0.017 0.093 -10000 0 -0.28 38 38
CSNK1A1 0.039 0.008 -10000 0 0 23 23
GNAS -0.014 0.099 0.2 16 -0.27 39 55
GO:0007205 -0.016 0.096 0.23 7 -0.24 45 52
WNT6 0.04 0.006 -10000 0 0 13 13
WNT4 0.04 0.008 -10000 0 0 19 19
NFAT1/CK1 alpha 0 0.12 0.28 4 -0.28 38 42
GNG2 0.039 0.009 -10000 0 0 29 29
WNT5A 0.034 0.015 -10000 0 0 89 89
WNT11 0.032 0.017 -10000 0 0 118 118
CDC42 -0.023 0.091 -10000 0 -0.26 41 41
HIF-2-alpha transcription factor network

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
MMP14 -0.056 0.29 -10000 0 -0.85 61 61
oxygen homeostasis 0.004 0.012 0.034 19 -0.025 6 25
TCEB2 0.039 0.008 -10000 0 0 23 23
TCEB1 0.038 0.011 -10000 0 0 39 39
VHL/Elongin B/Elongin C/HIF2A 0.04 0.14 0.29 11 -0.22 61 72
EPO 0.028 0.18 0.35 13 -0.34 36 49
FIH (dimer) 0.039 0.025 0.087 3 -0.035 41 44
APEX1 0.032 0.033 -10000 0 -0.035 74 74
SERPINE1 0 0.16 0.35 14 -0.32 58 72
FLT1 -0.047 0.26 -10000 0 -0.7 68 68
ADORA2A 0.018 0.17 0.33 34 -0.31 53 87
germ cell development 0.017 0.18 0.34 30 -0.31 64 94
SLC11A2 0.022 0.19 0.34 28 -0.33 59 87
BHLHE40 0.01 0.17 0.33 21 -0.31 60 81
HIF1AN 0.039 0.025 0.087 3 -0.035 41 44
HIF2A/ARNT/SIRT1 0.038 0.15 0.31 12 -0.25 56 68
ETS1 0.042 0.025 0.12 1 -0.11 5 6
CITED2 0.018 0.13 -10000 0 -0.62 20 20
KDR -0.04 0.25 -10000 0 -0.69 64 64
PGK1 0.023 0.19 0.35 30 -0.34 62 92
SIRT1 0.04 0.007 -10000 0 0 16 16
response to hypoxia 0 0 -10000 0 -10000 0 0
HIF2A/ARNT 0.053 0.22 0.47 1 -0.35 56 57
EPAS1 0.006 0.11 0.22 21 -0.22 70 91
SP1 0.034 0.048 -10000 0 -0.11 52 52
ABCG2 0.022 0.18 0.35 26 -0.32 56 82
EFNA1 0.01 0.19 0.34 25 -0.35 69 94
FXN 0.018 0.17 0.33 33 -0.31 56 89
POU5F1 0.016 0.18 0.35 29 -0.32 64 93
neuron apoptosis -0.051 0.21 0.34 56 -0.46 1 57
EP300 0.036 0.014 -10000 0 0 69 69
EGLN3 0.028 0.027 0.086 1 -0.034 23 24
EGLN2 0.038 0.024 0.088 3 -0.033 33 36
EGLN1 0.038 0.025 0.084 5 -0.035 40 45
VHL/Elongin B/Elongin C 0.069 0.038 -10000 0 -0.11 11 11
VHL 0.039 0.008 -10000 0 0 23 23
ARNT 0.032 0.032 -10000 0 -0.035 75 75
SLC2A1 -0.001 0.18 0.34 18 -0.33 67 85
TWIST1 0.017 0.17 0.33 34 -0.31 55 89
ELK1 0.046 0.013 -10000 0 -0.087 3 3
HIF2A/ARNT/Cbp/p300 0.038 0.16 0.33 13 -0.26 51 64
VEGFA 0.01 0.17 0.33 21 -0.31 60 81
CREBBP 0.037 0.012 -10000 0 0 53 53
TCR signaling in naïve CD8+ T cells

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
GRB2/SOS1/SHC 0.01 0.15 0.24 14 -0.34 55 69
FYN -0.032 0.18 0.26 13 -0.38 84 97
LAT/GRAP2/SLP76 -0.004 0.15 0.24 6 -0.33 66 72
IKBKB 0.038 0.011 -10000 0 0 41 41
AKT1 -0.016 0.14 0.22 10 -0.3 76 86
B2M 0.037 0.016 -10000 0 -0.004 66 66
IKBKG -0.003 0.049 0.12 12 -0.1 56 68
MAP3K8 0.039 0.008 -10000 0 0 24 24
mol:Ca2+ -0.014 0.014 0.038 8 -0.043 43 51
integrin-mediated signaling pathway 0.044 0.035 -10000 0 -0.11 24 24
LAT/GRAP2/SLP76/VAV1/PI3K Class IA -0.028 0.18 0.24 9 -0.41 77 86
TRPV6 0.076 0.33 1.3 37 -10000 0 37
CD28 0.041 0.007 -10000 0 0 13 13
SHC1 -0.014 0.16 0.23 18 -0.37 62 80
receptor internalization -0.015 0.14 0.17 3 -0.34 69 72
PRF1 -0.01 0.2 -10000 0 -0.76 29 29
KRAS 0.034 0.016 -10000 0 0 95 95
GRB2 0.04 0.008 -10000 0 0 21 21
COT/AKT1 0.003 0.12 0.22 9 -0.25 74 83
LAT -0.019 0.16 0.23 8 -0.36 67 75
EntrezGene:6955 0.001 0.003 -10000 0 -0.023 3 3
CD3D 0.034 0.018 -10000 0 -0.002 105 105
CD3E 0.036 0.016 -10000 0 -0.002 77 77
CD3G 0.032 0.019 -10000 0 -0.002 131 131
RASGRP2 0.009 0.019 0.074 1 -0.16 1 2
RASGRP1 -0.022 0.14 0.23 12 -0.31 82 94
HLA-A 0.038 0.015 -10000 0 -0.004 62 62
RASSF5 0.039 0.009 -10000 0 0 27 27
RAP1A/GTP/RAPL 0.045 0.036 -10000 0 -0.11 24 24
mol:GTP 0 0 -10000 0 -10000 0 0
mol:GDP 0.013 0.059 0.15 15 -0.11 43 58
PDK1/CARD11/BCL10/MALT1/TRAF6 -0.02 0.064 -10000 0 -0.15 80 80
PRKCA -0.008 0.081 0.19 11 -0.2 48 59
GRAP2 0.037 0.012 -10000 0 0 56 56
mol:IP3 -0.015 0.11 -10000 0 -0.26 64 64
EntrezGene:6957 0.001 0.004 -10000 0 -0.021 5 5
TCR/CD3/MHC I/CD8 -0.014 0.12 -10000 0 -0.38 41 41
ORAI1 -0.071 0.28 -10000 0 -1.1 37 37
CSK -0.015 0.16 0.25 7 -0.38 61 68
B7 family/CD28 0.022 0.16 0.26 5 -0.34 66 71
CHUK 0.038 0.011 -10000 0 0 46 46
TCR/CD3/MHC I/CD8/LCK/ZAP-70 -0.025 0.17 0.2 2 -0.37 75 77
PTPN6 -0.015 0.16 0.2 24 -0.35 69 93
VAV1 -0.018 0.16 0.22 12 -0.39 62 74
Monovalent TCR/CD3 -0.003 0.08 -10000 0 -0.21 60 60
CBL 0.04 0.008 -10000 0 0 20 20
LCK -0.022 0.17 0.25 12 -0.38 72 84
PAG1 -0.013 0.16 0.21 29 -0.37 64 93
RAP1A 0.039 0.01 -10000 0 0 35 35
TCR/CD3/MHC I/CD8/LCK -0.025 0.17 0.19 4 -0.37 77 81
CD80 0.039 0.01 -10000 0 0 32 32
CD86 0.034 0.016 -10000 0 0 99 99
PDK1/CARD11/BCL10/MALT1 -0.009 0.084 -10000 0 -0.18 76 76
HRAS 0.039 0.01 -10000 0 0 31 31
GO:0035030 -0.018 0.13 0.18 13 -0.3 67 80
CD8A 0.041 0.011 -10000 0 -0.018 16 16
CD8B 0.001 0.004 -10000 0 -0.021 6 6
PTPRC 0.025 0.02 -10000 0 0 222 222
PDK1/PKC theta -0.024 0.15 0.24 10 -0.35 71 81
CSK/PAG1 -0.012 0.16 0.22 31 -0.38 57 88
SOS1 0.037 0.012 -10000 0 0 51 51
peptide-MHC class I 0.037 0.071 -10000 0 -0.17 50 50
GRAP2/SLP76 -0.002 0.17 0.25 4 -0.38 66 70
STIM1 -0.013 0.13 1.3 4 -10000 0 4
RAS family/GTP 0.008 0.077 0.18 6 -0.16 53 59
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin -0.016 0.15 0.17 3 -0.35 69 72
mol:DAG -0.027 0.089 -10000 0 -0.23 67 67
RAP1A/GDP 0.01 0.032 0.076 14 -0.057 47 61
PLCG1 0.038 0.011 -10000 0 0 43 43
CD247 0.001 0.003 -10000 0 -0.023 3 3
cytotoxic T cell degranulation -0.008 0.2 -10000 0 -0.7 31 31
RAP1A/GTP 0.003 0.01 -10000 0 -0.034 18 18
mol:PI-3-4-5-P3 -0.02 0.16 0.22 11 -0.34 76 87
LAT/GRAP2/SLP76/VAV1/PLCgamma1 -0.01 0.14 0.22 1 -0.32 64 65
NRAS 0.039 0.009 -10000 0 0 30 30
ZAP70 0.041 0.005 -10000 0 0 9 9
GRB2/SOS1 0.047 0.044 -10000 0 -0.14 24 24
LAT/GRAP2/SLP76/VAV1 -0.012 0.14 0.25 5 -0.34 63 68
MALT1 0.036 0.014 -10000 0 0 70 70
TRAF6 0.04 0.008 -10000 0 0 19 19
CD8 heterodimer 0.031 0.012 -10000 0 -0.038 8 8
CARD11 0.037 0.012 -10000 0 0 55 55
PRKCB -0.027 0.061 -10000 0 -0.17 67 67
PRKCE -0.006 0.085 0.2 16 -0.2 47 63
PRKCQ -0.026 0.17 0.23 10 -0.39 73 83
LCP2 0.034 0.016 -10000 0 0 101 101
BCL10 0.041 0.005 -10000 0 0 8 8
regulation of survival gene product expression -0.011 0.12 0.2 12 -0.26 77 89
IKK complex 0.003 0.049 0.14 15 -0.091 30 45
RAS family/GDP -0.002 0.014 -10000 0 -0.034 44 44
MAP3K14 -0.003 0.091 0.16 13 -0.2 73 86
PDPK1 -0.018 0.13 0.22 11 -0.29 75 86
TCR/CD3/MHC I/CD8/Fyn -0.037 0.19 -10000 0 -0.47 65 65
BMP receptor signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS 0.009 0.1 -10000 0 -0.13 145 145
SMAD6-7/SMURF1 0.071 0.037 -10000 0 -0.14 9 9
NOG 0.038 0.012 -10000 0 0 48 48
SMAD9 0.015 0.1 -10000 0 -0.41 25 25
SMAD4 0.038 0.011 -10000 0 0 43 43
SMAD5 -0.001 0.094 0.19 3 -0.27 34 37
BMP7/USAG1 -0.021 0.085 -10000 0 -0.16 137 137
SMAD5/SKI 0.014 0.1 -10000 0 -0.28 33 33
SMAD1 0.007 0.091 -10000 0 -0.31 26 26
BMP2 0.038 0.01 -10000 0 0 38 38
SMAD1/SMAD1/SMAD4 0.031 0.096 -10000 0 -0.29 26 26
BMPR1A 0.036 0.013 -10000 0 0 66 66
BMPR1B 0.031 0.018 -10000 0 0 138 138
BMPR1A-1B/BAMBI 0.008 0.087 -10000 0 -0.14 119 119
AHSG 0.034 0.016 -10000 0 0 101 101
CER1 0.038 0.011 -10000 0 0 41 41
BMP2-4/CER1 0.061 0.043 -10000 0 -0.12 12 12
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA -0.009 0.1 0.18 1 -0.26 54 55
BMP2-4 (homodimer) 0.047 0.035 -10000 0 -0.13 12 12
RGMB 0.039 0.01 -10000 0 0 31 31
BMP6/BMPR2/BMPR1A-1B 0.049 0.086 -10000 0 -0.13 83 83
RGMA 0.039 0.009 -10000 0 0 29 29
SMURF1 0.04 0.006 -10000 0 0 13 13
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP -0.001 0.078 -10000 0 -0.24 32 32
BMP2-4/USAG1 0.022 0.071 -10000 0 -0.12 78 78
SMAD6/SMURF1/SMAD5 0.013 0.11 -10000 0 -0.28 36 36
SOSTDC1 0.023 0.02 -10000 0 0 244 244
BMP7/BMPR2/BMPR1A-1B 0.007 0.1 -10000 0 -0.13 153 153
SKI 0.039 0.009 -10000 0 0 29 29
BMP6 (homodimer) 0.038 0.011 -10000 0 0 46 46
HFE2 0.038 0.01 -10000 0 0 36 36
ZFYVE16 0.035 0.014 -10000 0 0 78 78
MAP3K7 0.038 0.01 -10000 0 0 38 38
BMP2-4/CHRD 0.054 0.044 -10000 0 -0.12 8 8
SMAD5/SMAD5/SMAD4 0.012 0.1 -10000 0 -0.27 35 35
MAPK1 0.038 0.011 -10000 0 0 44 44
TAK1/TAB family 0.036 0.12 -10000 0 -0.24 37 37
BMP7 (homodimer) 0.022 0.021 -10000 0 0 260 260
NUP214 0.038 0.011 -10000 0 0 43 43
BMP6/FETUA 0.045 0.027 -10000 0 -10000 0 0
SMAD1/SKI 0.027 0.095 -10000 0 -0.3 27 27
SMAD6 0.039 0.008 -10000 0 0 24 24
CTDSP2 0.039 0.009 -10000 0 0 29 29
BMP2-4/FETUA 0.054 0.045 -10000 0 -0.12 10 10
MAP3K7IP1 0.037 0.012 -10000 0 0 51 51
GREM1 0.034 0.015 -10000 0 0 91 91
BMPR2 (homodimer) 0.039 0.01 -10000 0 0 31 31
GADD34/PP1CA 0.058 0.054 -10000 0 -0.12 35 35
BMPR1A-1B (homodimer) 0.017 0.077 -10000 0 -0.15 88 88
CHRDL1 0.026 0.02 -10000 0 0 207 207
ENDOFIN/SMAD1 0.023 0.095 -10000 0 -0.3 25 25
SMAD6-7/SMURF1/SMAD1 0.054 0.11 -10000 0 -0.35 17 17
SMAD6/SMURF1 0.04 0.006 -10000 0 0 13 13
BAMBI 0.028 0.019 -10000 0 0 170 170
SMURF2 0.039 0.009 -10000 0 0 28 28
BMP2-4/CHRDL1 0.02 0.076 -10000 0 -0.12 101 101
BMP2-4/GREM1 0.053 0.048 -10000 0 -0.12 17 17
SMAD7 0.038 0.01 -10000 0 0 36 36
SMAD8A/SMAD8A/SMAD4 0.03 0.11 -10000 0 -0.39 30 30
SMAD1/SMAD6 0.027 0.097 -10000 0 -0.3 26 26
TAK1/SMAD6 0.052 0.035 -10000 0 -0.13 15 15
BMP7 0.022 0.021 -10000 0 0 260 260
BMP6 0.038 0.011 -10000 0 0 46 46
MAP3K7IP2 0.037 0.012 -10000 0 0 53 53
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1 0.002 0.082 -10000 0 -0.24 33 33
PPM1A 0.04 0.006 -10000 0 0 10 10
SMAD1/SMURF2 0.026 0.097 -10000 0 -0.31 24 24
SMAD7/SMURF1 0.054 0.028 -10000 0 -0.13 8 8
CTDSPL 0.04 0.007 -10000 0 0 15 15
PPP1CA 0.04 0.006 -10000 0 0 11 11
XIAP 0 0 -10000 0 -10000 0 0
CTDSP1 0.04 0.007 -10000 0 0 15 15
PPP1R15A 0.038 0.011 -10000 0 0 41 41
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS 0.002 0.084 0.17 4 -0.25 31 35
CHRD 0.033 0.016 -10000 0 0 105 105
BMPR2 0.039 0.01 -10000 0 0 31 31
BMP2-4/BMPR2/BMPR1A-1B/RGM -0.001 0.085 -10000 0 -0.26 31 31
BMP4 0.036 0.014 -10000 0 0 67 67
FST 0.033 0.017 -10000 0 0 111 111
BMP2-4/NOG 0.059 0.047 -10000 0 -0.12 19 19
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1 0.016 0.11 -10000 0 -0.13 150 150
IFN-gamma pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 0.038 0.087 0.24 1 -0.14 65 66
positive regulation of NF-kappaB transcription factor activity 0 0.001 -10000 0 -10000 0 0
CRKL 0.038 0.01 -10000 0 0 36 36
STAT1 (dimer)/Cbp/p300 0.006 0.12 0.27 10 -0.22 79 89
IFN-gammaR/JAK1/JAK1/JAK2/JAK2 0.039 0.081 -10000 0 -0.15 67 67
antigen processing and presentation of peptide antigen via MHC class I -0.024 0.094 -10000 0 -0.21 79 79
CaM/Ca2+ 0.042 0.087 0.23 1 -0.14 64 65
RAP1A 0.039 0.01 -10000 0 0 35 35
STAT1 (dimer)/SHP2 0.001 0.095 0.22 10 -0.19 62 72
AKT1 0.017 0.11 0.22 54 -0.22 28 82
MAP2K1 -0.023 0.073 0.15 40 -0.18 34 74
MAP3K11 -0.016 0.078 0.17 43 -0.18 30 73
IFNGR1 0.034 0.022 0.08 1 -0.037 19 20
mol:GTP 0 0 -10000 0 -10000 0 0
CaM/Ca2+/CAMKII 0.015 0.098 -10000 0 -0.29 36 36
Rap1/GTP -0.044 0.058 0.066 4 -0.18 48 52
CRKL/C3G 0.055 0.019 -10000 0 -10000 0 0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP 0.062 0.09 -10000 0 -0.14 60 60
CEBPB -0.02 0.16 0.29 2 -0.46 42 44
STAT3 0.038 0.011 -10000 0 0 41 41
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1 0.043 0.16 -10000 0 -0.78 16 16
STAT1 -0.025 0.087 0.18 31 -0.21 47 78
CALM1 0.039 0.009 -10000 0 0 26 26
IFN-gamma (dimer) 0.03 0.027 0.08 1 -0.038 58 59
PIK3CA 0.029 0.019 -10000 0 0 166 166
STAT1 (dimer)/PIAS1 -0.007 0.097 0.23 14 -0.2 50 64
CEBPB/PTGES2/Cbp/p300 -0.007 0.12 -10000 0 -0.31 41 41
mol:Ca2+ 0.034 0.085 0.23 1 -0.14 65 66
MAPK3 -0.014 0.13 -10000 0 -0.68 11 11
STAT1 (dimer) -0.021 0.14 0.18 7 -0.28 78 85
MAPK1 -0.042 0.2 -10000 0 -0.76 31 31
JAK2 0.031 0.024 -10000 0 -0.036 30 30
PIK3R1 0.034 0.016 -10000 0 0 99 99
JAK1 0.035 0.024 0.08 1 -0.037 45 46
CAMK2D 0.036 0.014 -10000 0 0 69 69
DAPK1 -0.019 0.16 0.28 1 -0.49 44 45
SMAD7 0.001 0.075 0.16 43 -0.13 51 94
CBL/CRKL/C3G 0.029 0.09 0.24 15 -0.17 35 50
PI3K 0.019 0.09 -10000 0 -0.18 53 53
IFNG 0.03 0.027 0.08 1 -0.038 58 59
apoptosis -0.007 0.14 0.26 2 -0.41 41 43
CAMK2G 0.04 0.008 -10000 0 0 21 21
STAT3 (dimer) 0.038 0.011 -10000 0 0 41 41
CAMK2A 0.04 0.006 -10000 0 0 12 12
CAMK2B 0.041 0.005 -10000 0 0 9 9
FRAP1 0.008 0.11 0.18 92 -0.21 32 124
PRKCD 0.013 0.12 0.23 49 -0.23 32 81
RAP1B 0.037 0.012 -10000 0 0 54 54
negative regulation of cell growth -0.024 0.094 -10000 0 -0.21 79 79
PTPN2 0.04 0.008 -10000 0 0 19 19
EP300 0.036 0.014 -10000 0 0 69 69
IRF1 -0.045 0.1 0.21 6 -0.28 58 64
STAT1 (dimer)/PIASy -0.024 0.093 0.19 32 -0.22 40 72
SOCS1 -0.002 0.19 -10000 0 -1.1 16 16
mol:GDP 0.026 0.085 0.22 15 -0.16 35 50
CASP1 -0.02 0.083 0.15 21 -0.16 98 119
PTGES2 0.04 0.008 -10000 0 0 22 22
IRF9 -0.005 0.052 0.11 15 -0.13 38 53
mol:PI-3-4-5-P3 0.005 0.08 -10000 0 -0.17 58 58
RAP1/GDP 0.016 0.09 0.2 4 -0.18 48 52
CBL -0.016 0.078 0.17 44 -0.18 26 70
MAP3K1 -0.017 0.076 0.16 40 -0.18 30 70
PIAS1 0.039 0.008 -10000 0 0 24 24
PIAS4 0.037 0.012 -10000 0 0 54 54
antigen processing and presentation of peptide antigen via MHC class II -0.024 0.094 -10000 0 -0.21 79 79
PTPN11 -0.011 0.078 0.17 42 -0.18 30 72
CREBBP 0.037 0.012 -10000 0 0 53 53
RAPGEF1 0.039 0.009 -10000 0 0 26 26
Retinoic acid receptors-mediated signaling

Figure S46.  Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S46.  Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
HDAC1 0.038 0.012 -10000 0 0 49 49
HDAC3 0.04 0.006 -10000 0 0 10 10
VDR 0.038 0.011 -10000 0 0 43 43
Cbp/p300/PCAF 0.039 0.043 -10000 0 -0.13 24 24
EP300 0.036 0.014 -10000 0 0 69 69
RARs/AIB1/Cbp/p300/PCAF/9cRA -0.016 0.099 -10000 0 -0.26 56 56
KAT2B 0 0 -10000 0 -10000 0 0
MAPK14 0.04 0.008 -10000 0 0 20 20
AKT1 0.011 0.091 0.19 19 -0.21 28 47
RAR alpha/9cRA/Cyclin H -0.006 0.12 -10000 0 -0.24 77 77
mol:9cRA 0 0 -10000 0 -10000 0 0
RARs/Src-1/Cbp/p300/PCAF/9cRA -0.004 0.082 -10000 0 -0.21 54 54
CDC2 0.026 0.023 -10000 0 -0.005 186 186
response to UV -0.001 0.008 -10000 0 -0.027 39 39
RAR alpha/Jnk1 0.015 0.068 -10000 0 -0.15 52 52
NCOR2 0.039 0.01 -10000 0 0 31 31
VDR/VDR/Vit D3 0.023 0.031 -10000 0 -0.12 22 22
RXRs/RARs/NRIP1/9cRA -0.041 0.19 0.28 1 -0.45 77 78
NCOA2 0.037 0.013 -10000 0 0 60 60
NCOA3 0.035 0.015 -10000 0 0 84 84
NCOA1 0.04 0.008 -10000 0 0 22 22
VDR/VDR/DNA 0.038 0.011 -10000 0 0 43 43
RARG 0.035 0.021 -10000 0 -0.018 67 67
RAR gamma1/9cRA 0.041 0.033 -10000 0 -0.11 15 15
MAPK3 0.035 0.022 -10000 0 -0.025 60 60
MAPK1 0.038 0.011 -10000 0 0 44 44
MAPK8 0.034 0.024 -10000 0 -0.026 70 70
mol:Vit D3 0 0 -10000 0 -10000 0 0
RXRs/VDR/DNA/Vit D3 -0.022 0.15 -10000 0 -0.31 95 95
RARA 0.006 0.054 -10000 0 -0.16 41 41
negative regulation of phosphoinositide 3-kinase cascade 0 0 -10000 0 -10000 0 0
RARs/TIF2/Cbp/p300/PCAF/9cRA -0.007 0.085 -10000 0 -0.22 55 55
PRKCA 0.03 0.032 -10000 0 -0.074 35 35
RXRs/RARs/NRIP1/9cRA/HDAC1 -0.051 0.2 -10000 0 -0.5 74 74
RXRG 0.013 0.057 -10000 0 -0.18 34 34
RXRA -0.028 0.098 -10000 0 -0.24 58 58
RXRB 0.011 0.059 -10000 0 -0.17 41 41
VDR/Vit D3/DNA 0.023 0.031 -10000 0 -0.12 22 22
RBP1 0.029 0.019 -10000 0 0 159 159
CRBP1/9-cic-RA 0.001 0.057 -10000 0 -0.12 91 91
RARB 0.031 0.026 -10000 0 -0.015 113 113
PRKCG 0.033 0.032 -10000 0 -0.072 41 41
MNAT1 0.04 0.007 -10000 0 0 18 18
RAR alpha/RXRs -0.022 0.16 0.27 2 -0.35 84 86
RXRs/RARs/SMRT(N-CoR2)/9cRA -0.014 0.13 0.24 2 -0.28 72 74
proteasomal ubiquitin-dependent protein catabolic process -0.016 0.11 0.16 2 -0.26 58 60
RXRs/RARs/NRIP1/9cRA/HDAC3 -0.05 0.2 -10000 0 -0.49 77 77
positive regulation of DNA binding -0.012 0.11 -10000 0 -0.22 83 83
NRIP1 -0.084 0.31 -10000 0 -0.95 55 55
RXRs/RARs -0.034 0.17 -10000 0 -0.39 83 83
RXRs/RXRs/DNA/9cRA -0.037 0.14 -10000 0 -0.32 91 91
PRKACA 0.035 0.015 -10000 0 0 84 84
CDK7 0.035 0.015 -10000 0 0 84 84
TFIIH 0.061 0.052 -10000 0 -0.13 25 25
RAR alpha/9cRA 0.036 0.086 -10000 0 -0.19 27 27
CCNH 0.037 0.012 -10000 0 0 51 51
CREBBP 0.037 0.012 -10000 0 0 53 53
RAR gamma2/9cRA 0.046 0.06 -10000 0 -0.13 35 35
Plasma membrane estrogen receptor signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
GNB1/GNG2 0.064 0.064 -10000 0 -0.1 50 50
ER alpha/Gai/GDP/Gbeta gamma -0.024 0.14 -10000 0 -0.3 77 77
AKT1 -0.086 0.26 -10000 0 -0.64 94 94
PIK3CA 0.029 0.019 -10000 0 0 166 166
E2/ER alpha (dimer)/PELP1/Src/PI3K -0.085 0.27 -10000 0 -0.65 95 95
mol:Ca2+ -0.001 0.071 0.18 10 -0.28 24 34
IGF1R 0.033 0.017 -10000 0 0 112 112
E2/ER alpha (dimer)/Striatin 0.034 0.05 -10000 0 -0.11 51 51
SHC1 0.039 0.008 -10000 0 0 23 23
apoptosis 0.083 0.25 0.61 94 -10000 0 94
RhoA/GTP 0.014 0.047 -10000 0 -0.11 57 57
E2/ER alpha (dimer)/PELP1/Src/p130 Cas -0.009 0.14 0.27 1 -0.29 69 70
regulation of stress fiber formation 0.015 0.069 0.16 16 -0.15 60 76
E2/ERA-ERB (dimer) 0.037 0.045 -10000 0 -0.11 42 42
KRAS 0.034 0.016 -10000 0 0 95 95
G13/GTP 0.033 0.045 -10000 0 -0.098 49 49
pseudopodium formation -0.015 0.069 0.15 60 -0.16 16 76
E2/ER alpha (dimer)/PELP1 0.035 0.046 -10000 0 -0.11 42 42
GRB2 0.04 0.008 -10000 0 0 21 21
GNG2 0.039 0.009 -10000 0 0 29 29
GNAO1 0.035 0.015 -10000 0 0 85 85
HRAS 0.039 0.01 -10000 0 0 31 31
mol:GTP 0 0 -10000 0 -10000 0 0
mol:NO -0.038 0.16 -10000 0 -0.38 79 79
E2/ER beta (dimer) 0.03 0.005 -10000 0 -10000 0 0
mol:GDP -0.002 0.075 0.14 2 -0.23 46 48
mol:NADP -0.038 0.16 -10000 0 -0.38 79 79
PIK3R1 0.034 0.016 -10000 0 0 99 99
mol:IP3 -0.003 0.071 0.18 7 -0.29 24 31
IGF-1R heterotetramer 0.033 0.017 -10000 0 0 112 112
PLCB1 0.004 0.068 -10000 0 -0.29 23 23
PLCB2 0.005 0.067 -10000 0 -0.28 25 25
IGF1 0.035 0.014 -10000 0 0 77 77
mol:L-citrulline -0.038 0.16 -10000 0 -0.38 79 79
RHOA 0.04 0.006 -10000 0 0 13 13
Gai/GDP -0.007 0.18 -10000 0 -0.59 44 44
JNK cascade 0.029 0.005 -10000 0 -10000 0 0
BCAR1 0.036 0.013 -10000 0 0 65 65
ESR2 0.04 0.007 -10000 0 0 15 15
GNAQ 0.038 0.012 -10000 0 0 48 48
ESR1 0.034 0.015 -10000 0 0 91 91
Gq family/GDP/Gbeta gamma -0.048 0.24 -10000 0 -0.66 67 67
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1 0.018 0.12 -10000 0 -0.66 11 11
E2/ER alpha (dimer)/PELP1/Src/p52 SHC -0.008 0.14 0.26 2 -0.29 73 75
GNAZ 0.038 0.011 -10000 0 0 46 46
E2/ER alpha (dimer) 0.016 0.041 -10000 0 -0.12 42 42
STRN 0.039 0.008 -10000 0 0 23 23
GNAL 0.04 0.008 -10000 0 0 22 22
PELP1 0.038 0.011 -10000 0 0 39 39
MAPK11 0.013 0.008 0.069 1 -10000 0 1
GNAI2 0.04 0.006 -10000 0 0 13 13
GNAI3 0.038 0.011 -10000 0 0 45 45
GNAI1 0.034 0.015 -10000 0 0 93 93
HBEGF -0.018 0.15 0.32 15 -0.33 57 72
cAMP biosynthetic process 0.031 0.038 -10000 0 -0.09 40 40
SRC -0.024 0.14 0.22 17 -0.29 79 96
PI3K 0.023 0.06 -10000 0 -0.15 44 44
GNB1 0.039 0.01 -10000 0 0 33 33
G13/GDP/Gbeta gamma 0.04 0.091 -10000 0 -0.2 47 47
SOS1 0.037 0.012 -10000 0 0 51 51
IGF-1R heterotetramer/IGF1 -0.037 0.1 -10000 0 -0.25 74 74
Gs family/GTP 0.041 0.043 -10000 0 -0.091 40 40
EntrezGene:2778 0 0 -10000 0 -10000 0 0
RAS family/GTP 0.054 0.049 -10000 0 -0.11 27 27
vasodilation -0.035 0.16 -10000 0 -0.36 79 79
mol:DAG -0.003 0.071 0.18 7 -0.29 24 31
Gs family/GDP/Gbeta gamma 0.005 0.078 -10000 0 -0.21 45 45
MSN -0.016 0.072 0.15 60 -0.17 16 76
Gq family/GTP 0.018 0.072 -10000 0 -0.28 25 25
mol:PI-3-4-5-P3 -0.081 0.26 -10000 0 -0.62 96 96
NRAS 0.039 0.009 -10000 0 0 30 30
mol:E2 0 0 -10000 0 -10000 0 0
cell adhesion 0.035 0.16 0.36 79 -10000 0 79
GRB2/SOS1 0.047 0.044 -10000 0 -0.14 24 24
RhoA/GDP 0.016 0.086 -10000 0 -0.22 49 49
NOS3 -0.04 0.17 -10000 0 -0.4 79 79
GNA11 0.037 0.013 -10000 0 0 61 61
MAPKKK cascade -0.03 0.18 -10000 0 -0.46 74 74
E2/ER alpha (dimer)/PELP1/Src -0.014 0.14 0.27 2 -0.3 76 78
ruffle organization -0.015 0.069 0.15 60 -0.16 16 76
ROCK2 -0.009 0.079 0.17 67 -0.17 7 74
GNA14 0.039 0.009 -10000 0 0 29 29
GNA15 0.036 0.014 -10000 0 0 68 68
GNA13 0.039 0.008 -10000 0 0 23 23
MMP9 -0.02 0.15 0.36 15 -0.31 65 80
MMP2 -0.021 0.14 0.23 13 -0.32 57 70
Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2 -0.001 0.07 0.14 13 -0.18 60 73
CRKL 0.038 0.01 -10000 0 0 36 36
Rac1/GDP 0.029 0.009 -10000 0 -0.12 1 1
DOCK1 0.037 0.012 -10000 0 0 53 53
ITGA4 0.035 0.015 -10000 0 0 88 88
alpha4/beta7 Integrin/MAdCAM1 0.063 0.074 -10000 0 -0.11 68 68
EPO 0.04 0.007 -10000 0 0 14 14
alpha4/beta7 Integrin 0.031 0.065 -10000 0 -0.14 66 66
mol:GTP 0 0 -10000 0 -10000 0 0
CRK 0.038 0.012 -10000 0 0 49 49
alpha4/beta1 Integrin 0.031 0.065 -10000 0 -0.14 66 66
EPO/EPOR (dimer) 0.051 0.025 -10000 0 -0.13 2 2
lamellipodium assembly 0.021 0.11 -10000 0 -0.41 14 14
PIK3CA 0.029 0.019 -10000 0 0 166 166
PI3K 0.023 0.06 -10000 0 -0.15 44 44
ARF6 0.04 0.007 -10000 0 0 16 16
JAK2 0.002 0.075 -10000 0 -0.2 58 58
PXN 0.04 0.006 -10000 0 0 10 10
PIK3R1 0.034 0.016 -10000 0 0 99 99
MADCAM1 0.036 0.014 -10000 0 0 67 67
cell adhesion 0.061 0.072 -10000 0 -0.11 68 68
CRKL/CBL 0.055 0.02 -10000 0 -0.13 1 1
ITGB1 0.038 0.01 -10000 0 0 36 36
SRC -0.019 0.091 0.2 23 -0.19 43 66
ITGB7 0.038 0.01 -10000 0 0 38 38
RAC1 0.039 0.009 -10000 0 0 28 28
alpha4/beta1 Integrin/VCAM1 -0.007 0.096 -10000 0 -0.14 154 154
p130Cas/Crk/Dock1 0.013 0.1 0.23 19 -0.18 45 64
VCAM1 0.02 0.021 -10000 0 0 281 281
RHOA 0.04 0.006 -10000 0 0 13 13
alpha4/beta1 Integrin/Paxillin/GIT1 0.069 0.073 -10000 0 -0.11 65 65
BCAR1 -0.018 0.081 0.2 20 -0.18 39 59
EPOR 0.036 0.014 -10000 0 0 74 74
mol:GDP 0 0 -10000 0 -10000 0 0
CBL 0.04 0.008 -10000 0 0 20 20
GIT1 0.039 0.009 -10000 0 0 25 25
Rac1/GTP 0.02 0.11 -10000 0 -0.44 13 13
EPHB forward signaling

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
Ephrin A5/EPHB2 0.035 0.047 -10000 0 -0.11 43 43
cell-cell adhesion 0.042 0.041 0.17 13 -10000 0 13
Ephrin B/EPHB2/RasGAP 0.052 0.095 -10000 0 -0.12 97 97
ITSN1 0.04 0.007 -10000 0 0 15 15
PIK3CA 0.029 0.019 -10000 0 0 166 166
SHC1 0.039 0.008 -10000 0 0 23 23
Ephrin B1/EPHB3 0.037 0.037 -10000 0 -0.11 21 21
Ephrin B1/EPHB1 0.048 0.023 -10000 0 -0.11 5 5
HRAS/GDP -0.019 0.11 0.19 1 -0.18 131 132
Ephrin B/EPHB1/GRB7 0.056 0.088 -10000 0 -0.11 84 84
Endophilin/SYNJ1 -0.025 0.059 0.19 11 -0.2 6 17
KRAS 0.034 0.016 -10000 0 0 95 95
Ephrin B/EPHB1/Src 0.059 0.087 -10000 0 -0.11 80 80
endothelial cell migration 0.02 0.074 -10000 0 -0.11 94 94
GRB2 0.04 0.008 -10000 0 0 21 21
GRB7 0.037 0.013 -10000 0 0 57 57
PAK1 -0.019 0.071 0.18 27 -0.19 11 38
HRAS 0.039 0.01 -10000 0 0 31 31
RRAS -0.025 0.058 0.19 8 -0.19 11 19
DNM1 0.039 0.01 -10000 0 0 33 33
cell-cell signaling 0 0 -10000 0 -10000 0 0
CRK -0.012 0.07 0.19 31 -0.17 4 35
lamellipodium assembly -0.042 0.041 -10000 0 -0.17 13 13
Ephrin B/EPHB1/Src/p52 SHC/GRB2 0.004 0.071 -10000 0 -0.2 13 13
PIK3R1 0.034 0.016 -10000 0 0 99 99
EPHB2 0.038 0.01 -10000 0 0 38 38
EPHB3 0.032 0.017 -10000 0 0 126 126
EPHB1 0.037 0.012 -10000 0 0 50 50
EPHB4 0.039 0.008 -10000 0 0 23 23
mol:GDP -0.043 0.095 0.19 9 -0.22 72 81
Ephrin B/EPHB2 0.045 0.079 -10000 0 -0.11 95 95
Ephrin B/EPHB3 0.035 0.075 -10000 0 -0.11 86 86
JNK cascade -0.008 0.092 0.3 37 -0.18 2 39
Ephrin B/EPHB1 0.047 0.074 -10000 0 -0.11 83 83
RAP1/GDP -0.028 0.12 0.33 2 -0.21 85 87
EFNB2 0.031 0.018 -10000 0 0 139 139
EFNB3 0.036 0.014 -10000 0 0 69 69
EFNB1 0.04 0.007 -10000 0 0 15 15
Ephrin B2/EPHB1-2 0.035 0.067 -10000 0 -0.11 78 78
RAP1B 0.037 0.012 -10000 0 0 54 54
RAP1A 0.039 0.01 -10000 0 0 35 35
CDC42/GTP 0.027 0.098 -10000 0 -0.16 82 82
Rap1/GTP -0.046 0.05 0.06 3 -0.19 15 18
axon guidance 0.035 0.047 -10000 0 -0.11 43 43
MAPK3 -0.004 0.069 0.18 10 -0.22 8 18
MAPK1 -0.001 0.068 0.19 13 -0.21 8 21
Rac1/GDP -0.032 0.11 0.28 4 -0.21 80 84
actin cytoskeleton reorganization -0.053 0.06 -10000 0 -0.16 70 70
CDC42/GDP -0.032 0.11 0.28 4 -0.22 78 82
PI3K 0.023 0.077 -10000 0 -0.12 94 94
EFNA5 0.034 0.015 -10000 0 0 93 93
Ephrin B2/EPHB4 0.023 0.06 -10000 0 -0.11 82 82
Ephrin B/EPHB2/Intersectin/N-WASP 0 0.08 -10000 0 -0.16 96 96
CDC42 0.04 0.007 -10000 0 0 18 18
RAS family/GTP -0.041 0.048 -10000 0 -0.18 15 15
PTK2 0.14 0.26 0.56 146 -0.18 2 148
MAP4K4 -0.008 0.092 0.3 37 -0.18 2 39
SRC 0.039 0.009 -10000 0 0 28 28
KALRN 0.038 0.012 -10000 0 0 47 47
Intersectin/N-WASP 0.056 0.022 -10000 0 -0.13 5 5
neuron projection morphogenesis -0.024 0.088 0.28 16 -0.21 16 32
MAP2K1 -0.003 0.064 0.17 1 -0.2 10 11
WASL 0.04 0.007 -10000 0 0 18 18
Ephrin B1/EPHB1-2/NCK1 0.076 0.063 -10000 0 -0.11 40 40
cell migration -0.011 0.089 0.24 7 -0.24 13 20
NRAS 0.039 0.009 -10000 0 0 30 30
SYNJ1 -0.025 0.06 0.19 11 -0.2 6 17
PXN 0.04 0.006 -10000 0 0 10 10
TF -0.029 0.054 0.17 10 -0.2 6 16
HRAS/GTP 0.031 0.079 -10000 0 -0.12 90 90
Ephrin B1/EPHB1-2 0.062 0.041 -10000 0 -0.11 17 17
cell adhesion mediated by integrin 0.009 0.062 0.17 9 -0.21 14 23
RAC1 0.039 0.009 -10000 0 0 28 28
mol:GTP 0.035 0.081 -10000 0 -0.12 92 92
RAC1-CDC42/GTP -0.041 0.045 -10000 0 -0.2 8 8
RASA1 0.037 0.013 -10000 0 0 56 56
RAC1-CDC42/GDP -0.021 0.11 0.29 4 -0.21 77 81
ruffle organization -0.025 0.077 0.24 11 -0.24 2 13
NCK1 0.036 0.014 -10000 0 0 70 70
receptor internalization -0.03 0.056 0.18 11 -0.19 8 19
Ephrin B/EPHB2/KALRN 0.056 0.092 -10000 0 -0.12 89 89
ROCK1 0.018 0.087 0.19 102 -10000 0 102
RAS family/GDP -0.057 0.063 -10000 0 -0.16 107 107
Rac1/GTP -0.042 0.046 -10000 0 -0.19 11 11
Ephrin B/EPHB1/Src/Paxillin 0.002 0.073 -10000 0 -0.15 83 83
FAS signaling pathway (CD95)

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
SPTAN1 -0.026 0.053 0.18 2 -0.21 33 35
RFC1 -0.025 0.056 0.18 4 -0.21 35 39
PRKDC -0.019 0.069 0.21 18 -0.21 37 55
RIPK1 0.038 0.01 -10000 0 0 32 32
CASP7 0.006 0.11 -10000 0 -0.57 16 16
FASLG/FAS/FADD/FAF1 0.023 0.08 0.15 100 -0.17 37 137
MAP2K4 0.009 0.11 0.22 6 -0.33 29 35
mol:ceramide 0.017 0.091 -10000 0 -0.31 19 19
GSN -0.026 0.051 0.13 1 -0.21 34 35
FASLG/FAS/FADD/FAF1/Caspase 8 0.024 0.087 0.19 9 -0.24 20 29
FAS 0.035 0.017 -10000 0 -0.002 93 93
BID -0.03 0.018 0.23 1 -10000 0 1
MAP3K1 0.016 0.11 0.25 7 -0.36 22 29
MAP3K7 0.039 0.011 -10000 0 -0.001 39 39
RB1 -0.023 0.059 0.2 7 -0.2 32 39
CFLAR 0.039 0.008 -10000 0 0 19 19
HGF/MET -0.013 0.091 -10000 0 -0.14 167 167
ARHGDIB -0.015 0.073 0.21 24 -0.21 28 52
FADD 0.04 0.012 -10000 0 -0.009 26 26
actin filament polymerization 0.026 0.055 0.21 37 -10000 0 37
NFKB1 -0.035 0.22 -10000 0 -0.67 57 57
MAPK8 0.006 0.11 0.24 1 -0.37 24 25
DFFA -0.024 0.055 0.18 4 -0.21 38 42
DNA fragmentation during apoptosis -0.023 0.058 0.18 4 -0.21 39 43
FAS/FADD/MET 0.018 0.087 -10000 0 -0.13 124 124
CFLAR/RIP1 0.053 0.03 -10000 0 -0.15 8 8
FAIM3 0.04 0.007 -10000 0 0 15 15
FAF1 0.04 0.014 -10000 0 -0.01 33 33
PARP1 -0.021 0.063 0.22 13 -0.2 35 48
DFFB -0.023 0.054 0.18 4 -0.21 36 40
CHUK -0.042 0.21 -10000 0 -0.64 55 55
FASLG 0.04 0.013 -10000 0 -0.011 28 28
FAS/FADD 0.038 0.059 -10000 0 -0.13 52 52
HGF 0.039 0.009 -10000 0 0 27 27
LMNA -0.018 0.066 0.21 15 -0.21 27 42
CASP6 -0.019 0.054 0.14 2 -0.22 23 25
CASP10 0.036 0.016 -10000 0 -0.004 72 72
CASP3 -0.02 0.059 0.16 2 -0.23 37 39
PTPN13 0.021 0.021 -10000 0 0 268 268
CASP8 -0.032 0.016 0.26 1 -10000 0 1
IL6 -0.026 0.23 -10000 0 -0.74 32 32
MET 0.027 0.02 -10000 0 0 191 191
ICAD/CAD -0.026 0.054 0.19 5 -0.2 37 42
FASLG/FAS/FADD/FAF1/Caspase 10 0.017 0.092 -10000 0 -0.31 19 19
activation of caspase activity by cytochrome c -0.03 0.018 0.23 1 -10000 0 1
PAK2 0.005 0.095 0.22 69 -0.21 32 101
BCL2 0.036 0.013 -10000 0 0 67 67
BCR signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
JUN -0.043 0.14 0.3 1 -0.34 64 65
IKBKB 0.021 0.092 0.27 8 -0.28 13 21
AKT1 0.027 0.1 0.24 49 -0.19 14 63
IKBKG 0.021 0.076 0.22 3 -0.25 12 15
CALM1 -0.012 0.11 0.21 6 -0.34 37 43
PIK3CA 0.029 0.019 -10000 0 0 166 166
MAP3K1 -0.032 0.15 -10000 0 -0.42 44 44
MAP3K7 0.038 0.01 -10000 0 0 38 38
mol:Ca2+ -0.01 0.12 0.21 4 -0.34 43 47
DOK1 0.04 0.008 -10000 0 0 22 22
AP-1 -0.022 0.095 0.18 1 -0.22 61 62
LYN 0.035 0.015 -10000 0 0 83 83
BLNK 0.037 0.013 -10000 0 0 62 62
SHC1 0.039 0.008 -10000 0 0 23 23
BCR complex 0.052 0.025 -10000 0 -0.12 3 3
CD22 -0.016 0.094 -10000 0 -0.28 43 43
CAMK2G -0.013 0.11 0.2 14 -0.32 39 53
CSNK2A1 0.038 0.012 -10000 0 0 47 47
INPP5D 0 0 -10000 0 -10000 0 0
SHC/GRB2/SOS1 0.02 0.062 -10000 0 -0.13 57 57
GO:0007205 -0.011 0.12 0.21 4 -0.34 45 49
SYK 0.036 0.014 -10000 0 0 67 67
ELK1 -0.015 0.12 0.22 3 -0.34 44 47
NFATC1 -0.033 0.11 0.21 2 -0.3 45 47
B-cell antigen/BCR complex 0.052 0.025 -10000 0 -0.12 3 3
PAG1/CSK 0.052 0.026 -10000 0 -0.13 4 4
NFKBIB 0.017 0.062 0.13 2 -0.13 64 66
HRAS -0.011 0.1 0.22 4 -0.28 44 48
NFKBIA 0.019 0.057 0.13 2 -0.12 54 56
NF-kappa-B/RelA/I kappa B beta 0.024 0.055 0.12 5 -0.1 60 65
RasGAP/Csk 0.056 0.086 -10000 0 -0.11 83 83
mol:GDP -0.011 0.12 0.2 4 -0.34 44 48
PTEN 0.039 0.01 -10000 0 0 36 36
CD79B 0.04 0.007 -10000 0 0 16 16
NF-kappa-B/RelA/I kappa B alpha 0.026 0.052 0.12 5 -0.1 52 57
GRB2 0.04 0.008 -10000 0 0 21 21
PI3K/BCAP/CD19 -0.026 0.15 -10000 0 -0.42 42 42
PIK3R1 0.034 0.016 -10000 0 0 99 99
mol:IP3 -0.006 0.12 0.21 4 -0.36 38 42
CSK 0.039 0.009 -10000 0 0 25 25
FOS -0.015 0.12 0.22 7 -0.33 43 50
CHUK 0.001 0.11 0.22 3 -0.27 50 53
IBTK 0.036 0.013 -10000 0 0 64 64
CARD11/BCL10/MALT1/TAK1 0.014 0.12 -10000 0 -0.31 38 38
PTPN6 -0.01 0.095 0.18 24 -0.28 36 60
RELA 0.04 0.006 -10000 0 0 10 10
BCL2A1 0.016 0.042 0.098 2 -0.08 60 62
VAV2 -0.025 0.12 -10000 0 -0.33 52 52
ubiquitin-dependent protein catabolic process 0.02 0.06 -10000 0 -0.12 64 64
BTK -0.038 0.25 -10000 0 -1.1 31 31
CD19 -0.019 0.1 -10000 0 -0.29 42 42
MAP4K1 0.036 0.014 -10000 0 0 67 67
CD72 0.04 0.006 -10000 0 0 12 12
PAG1 0.037 0.012 -10000 0 0 50 50
MAPK14 -0.029 0.14 0.31 3 -0.36 45 48
SH3BP5 0.04 0.008 -10000 0 0 22 22
PIK3AP1 -0.01 0.12 0.24 3 -0.39 34 37
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72 -0.015 0.16 -10000 0 -0.46 44 44
RAF1 -0.014 0.097 0.21 9 -0.28 40 49
RasGAP/p62DOK/SHIP 0.044 0.077 -10000 0 -0.1 89 89
CD79A 0.036 0.013 -10000 0 0 63 63
re-entry into mitotic cell cycle -0.022 0.094 -10000 0 -0.22 59 59
RASA1 0.037 0.013 -10000 0 0 56 56
MAPK3 -0.019 0.087 0.22 8 -0.25 37 45
MAPK1 -0.017 0.088 0.23 10 -0.25 34 44
CD72/SHP1 0.023 0.12 0.29 20 -0.27 35 55
NFKB1 0.036 0.013 -10000 0 0 66 66
MAPK8 -0.031 0.13 -10000 0 -0.37 43 43
actin cytoskeleton organization -0.026 0.11 0.25 3 -0.3 47 50
NF-kappa-B/RelA 0.04 0.12 -10000 0 -0.23 64 64
Calcineurin 0.013 0.12 0.28 1 -0.3 38 39
PI3K -0.015 0.079 -10000 0 -0.25 26 26
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2 -0.001 0.12 0.22 4 -0.38 36 40
SOS1 0.037 0.012 -10000 0 0 51 51
Bam32/HPK1 -0.037 0.23 -10000 0 -0.69 46 46
DAPP1 -0.058 0.25 -10000 0 -0.77 49 49
cytokine secretion -0.03 0.1 0.21 2 -0.29 45 47
mol:DAG -0.006 0.12 0.21 4 -0.36 38 42
PLCG2 0.035 0.015 -10000 0 0 82 82
MAP2K1 -0.017 0.092 0.21 9 -0.27 37 46
B-cell antigen/BCR complex/FcgammaRIIB 0.037 0.07 -10000 0 -0.12 74 74
mol:PI-3-4-5-P3 0.015 0.1 0.23 43 -0.22 14 57
ETS1 -0.011 0.11 0.22 12 -0.32 36 48
B-cell antigen/BCR complex/LYN/SYK/BLNK 0.068 0.082 -10000 0 -0.12 58 58
B-cell antigen/BCR complex/LYN -0.014 0.1 -10000 0 -0.3 42 42
MALT1 0.036 0.014 -10000 0 0 70 70
TRAF6 0.04 0.008 -10000 0 0 19 19
RAC1 -0.027 0.12 0.26 3 -0.31 48 51
B-cell antigen/BCR complex/LYN/SYK 0.046 0.12 0.34 11 -0.25 22 33
CARD11 -0.012 0.12 0.22 5 -0.36 37 42
FCGR2B 0.03 0.019 -10000 0 0 153 153
PPP3CA 0.038 0.011 -10000 0 0 45 45
BCL10 0.041 0.005 -10000 0 0 8 8
IKK complex 0.02 0.051 0.15 19 -0.11 16 35
PTPRC 0.024 0.02 -10000 0 0 222 222
PDPK1 0.018 0.092 0.21 54 -0.17 12 66
PPP3CB 0.039 0.009 -10000 0 0 28 28
PPP3CC 0.033 0.016 -10000 0 0 103 103
POU2F2 0.016 0.042 0.12 8 -0.077 62 70
ErbB4 signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF -0.025 0.2 -10000 0 -0.68 39 39
epithelial cell differentiation -0.031 0.19 -10000 0 -0.61 42 42
ITCH 0.038 0.038 0.1 10 -0.094 30 40
WWP1 -0.061 0.28 0.32 1 -1.2 31 32
FYN 0.034 0.016 -10000 0 0 94 94
EGFR 0.036 0.014 -10000 0 0 67 67
PRL 0.039 0.01 -10000 0 0 31 31
neuron projection morphogenesis -0.042 0.16 0.23 9 -0.56 35 44
PTPRZ1 0.039 0.01 -10000 0 0 32 32
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC 0.005 0.18 -10000 0 -0.61 35 35
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta -0.033 0.18 -10000 0 -0.65 37 37
ADAM17 0.037 0.035 0.097 6 -0.08 30 36
ErbB4/ErbB4 -0.05 0.21 -10000 0 -0.84 32 32
ErbB4/ErbB4/neuregulin 3/neuregulin 3 -0.03 0.2 -10000 0 -0.65 41 41
NCOR1 0.037 0.013 -10000 0 0 58 58
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn -0.026 0.18 -10000 0 -0.6 40 40
GRIN2B -0.034 0.16 0.24 3 -0.56 40 43
ErbB4/ErbB2/betacellulin -0.025 0.18 -10000 0 -0.55 46 46
STAT1 0.034 0.016 -10000 0 0 102 102
HBEGF 0.039 0.009 -10000 0 0 27 27
PRLR 0.035 0.015 -10000 0 0 80 80
E4ICDs/ETO2 -0.029 0.2 -10000 0 -0.68 39 39
axon guidance -0.054 0.22 -10000 0 -0.76 41 41
NEDD4 0.036 0.039 0.1 7 -0.082 39 46
Prolactin receptor/Prolactin receptor/Prolactin 0.05 0.024 -10000 0 -10000 0 0
CBFA2T3 0.035 0.015 -10000 0 0 82 82
ErbB4/ErbB2/HBEGF -0.018 0.18 -10000 0 -0.57 43 43
MAPK3 -0.024 0.16 0.28 4 -0.58 35 39
STAT1 (dimer) -0.034 0.21 -10000 0 -0.52 60 60
MAPK1 -0.024 0.16 0.26 6 -0.58 35 41
JAK2 0.034 0.016 -10000 0 0 101 101
ErbB4/ErbB2/neuregulin 1 beta -0.03 0.17 0.19 2 -0.64 36 38
NRG1 -0.007 0.032 0.035 111 -0.11 21 132
NRG3 0.034 0.015 -10000 0 0 91 91
NRG2 0.041 0.005 -10000 0 0 8 8
NRG4 0.028 0.019 -10000 0 0 169 169
heart development -0.054 0.22 -10000 0 -0.76 41 41
neural crest cell migration -0.029 0.17 0.19 2 -0.63 36 38
ERBB2 -0.009 0.032 0.035 111 -0.098 25 136
WWOX/E4ICDs -0.029 0.2 -10000 0 -0.69 37 37
SHC1 0.039 0.008 -10000 0 0 23 23
ErbB4/EGFR/neuregulin 4 -0.036 0.2 -10000 0 -0.68 38 38
apoptosis 0.03 0.19 0.63 43 -10000 0 43
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta -0.024 0.21 -10000 0 -0.68 39 39
ErbB4/ErbB2/epiregulin -0.018 0.18 -10000 0 -0.57 42 42
ErbB4/ErbB4/betacellulin/betacellulin -0.034 0.2 -10000 0 -0.61 47 47
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2 0.005 0.2 -10000 0 -0.63 36 36
MDM2 -0.042 0.19 0.27 11 -0.72 33 44
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta -0.02 0.16 -10000 0 -0.57 37 37
STAT5A -0.058 0.22 0.24 1 -0.73 42 43
ErbB4/EGFR/neuregulin 1 beta -0.025 0.18 -10000 0 -0.63 37 37
DLG4 0.038 0.01 -10000 0 0 38 38
GRB2/SHC 0.055 0.022 -10000 0 -0.13 4 4
E4ICDs/TAB2/NCoR1 -0.019 0.21 -10000 0 -0.65 41 41
STAT5A (dimer) -0.025 0.22 -10000 0 -0.68 42 42
MAP3K7IP2 0.037 0.012 -10000 0 0 53 53
STAT5B (dimer) -0.037 0.23 -10000 0 -0.74 42 42
LRIG1 0.033 0.017 -10000 0 0 112 112
EREG 0.038 0.011 -10000 0 0 42 42
BTC 0.033 0.016 -10000 0 0 105 105
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta -0.058 0.23 -10000 0 -0.77 41 41
ERBB4 -0.049 0.2 -10000 0 -0.84 31 31
STAT5B 0.039 0.009 -10000 0 0 27 27
YAP1 0.002 0.094 -10000 0 -0.54 14 14
GRB2 0.04 0.008 -10000 0 0 21 21
ErbB4/ErbB2/neuregulin 4 -0.03 0.18 -10000 0 -0.62 38 38
glial cell differentiation 0.019 0.2 0.64 41 -10000 0 41
WWOX 0.029 0.019 -10000 0 0 156 156
cell proliferation -0.068 0.22 0.28 1 -0.6 58 59
E-cadherin signaling in the nascent adherens junction

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
CTTN -0.032 0.14 -10000 0 -0.34 80 80
KLHL20 -0.015 0.1 0.21 12 -0.23 53 65
CYFIP2 0.038 0.011 -10000 0 0 45 45
Rac1/GDP -0.007 0.11 0.26 8 -0.25 45 53
ENAH -0.029 0.14 -10000 0 -0.35 74 74
AP1M1 0.036 0.014 -10000 0 0 72 72
RAP1B 0.037 0.012 -10000 0 0 54 54
RAP1A 0.039 0.01 -10000 0 0 35 35
CTNNB1 0.039 0.01 -10000 0 0 32 32
CDC42/GTP 0.005 0.077 0.16 2 -0.2 31 33
ABI1/Sra1/Nap1 -0.033 0.055 -10000 0 -0.15 69 69
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin 0.068 0.067 -10000 0 -0.11 43 43
RAPGEF1 -0.027 0.12 0.27 4 -0.31 68 72
CTNND1 0.04 0.007 -10000 0 0 17 17
regulation of calcium-dependent cell-cell adhesion -0.019 0.14 -10000 0 -0.35 78 78
CRK -0.023 0.13 0.25 1 -0.34 64 65
E-cadherin/gamma catenin/alpha catenin 0.053 0.063 -10000 0 -0.14 41 41
alphaE/beta7 Integrin 0.048 0.038 -10000 0 -0.13 17 17
IQGAP1 0.036 0.013 -10000 0 0 66 66
NCKAP1 0.039 0.009 -10000 0 0 26 26
Rap1/GTP/I-afadin 0.043 0.063 -10000 0 -0.11 61 61
DLG1 -0.027 0.13 -10000 0 -0.35 63 63
ChemicalAbstracts:7440-70-2 0 0 -10000 0 -10000 0 0
mol:PI-3-4-5-P3 -0.028 0.044 -10000 0 -0.15 40 40
MLLT4 0.033 0.016 -10000 0 0 109 109
ARF6/GTP/NME1/Tiam1 0.047 0.062 -10000 0 -0.11 61 61
PI3K -0.034 0.058 -10000 0 -0.19 40 40
ARF6 0.04 0.007 -10000 0 0 16 16
mol:Ca2+ 0 0 -10000 0 -10000 0 0
E-cadherin/gamma catenin 0.04 0.051 -10000 0 -0.15 30 30
TIAM1 0.036 0.013 -10000 0 0 66 66
E-cadherin(dimer)/Ca2+ 0.065 0.069 -10000 0 -0.12 48 48
AKT1 0.009 0.076 0.16 65 -0.16 16 81
PIK3R1 0.034 0.016 -10000 0 0 99 99
CDH1 0.035 0.015 -10000 0 0 79 79
RhoA/GDP -0.009 0.11 0.25 4 -0.25 48 52
actin cytoskeleton organization -0.009 0.078 0.17 12 -0.17 52 64
CDC42/GDP -0.007 0.11 0.27 6 -0.25 45 51
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin 0.001 0.075 -10000 0 -0.2 56 56
ITGB7 0.038 0.01 -10000 0 0 38 38
RAC1 0.039 0.009 -10000 0 0 28 28
E-cadherin/beta catenin/alpha catenin/p120 catenin 0.07 0.074 -10000 0 -0.13 48 48
E-cadherin/Ca2+/beta catenin/alpha catenin 0.048 0.053 -10000 0 -0.1 45 45
mol:GDP -0.026 0.11 0.25 8 -0.28 48 56
CDC42/GTP/IQGAP1 0.039 0.046 -10000 0 -0.11 42 42
JUP 0.037 0.013 -10000 0 0 57 57
p120 catenin/RhoA/GDP 0.003 0.11 0.26 4 -0.26 44 48
RAC1/GTP/IQGAP1 0.039 0.045 -10000 0 -0.11 40 40
PIP5K1C/AP1M1 0.048 0.026 -10000 0 -0.13 1 1
RHOA 0.04 0.006 -10000 0 0 13 13
CDC42 0.04 0.007 -10000 0 0 18 18
CTNNA1 0.039 0.01 -10000 0 0 31 31
positive regulation of S phase of mitotic cell cycle -0.016 0.058 0.1 4 -0.12 103 107
NME1 0.036 0.014 -10000 0 0 71 71
clathrin coat assembly 0 0 -10000 0 -10000 0 0
TJP1 -0.03 0.14 -10000 0 -0.36 72 72
regulation of cell-cell adhesion -0.009 0.06 -10000 0 -0.15 47 47
WASF2 -0.007 0.043 0.11 13 -0.092 50 63
Rap1/GTP 0.004 0.084 0.19 18 -0.23 26 44
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin 0.073 0.081 -10000 0 -0.12 48 48
CCND1 -0.02 0.071 0.12 2 -0.14 105 107
VAV2 -0.047 0.22 -10000 0 -0.6 56 56
RAP1/GDP 0.004 0.095 0.22 9 -0.26 26 35
adherens junction assembly -0.031 0.14 -10000 0 -0.34 75 75
homophilic cell adhesion 0 0 -10000 0 -10000 0 0
ABI1 0.039 0.009 -10000 0 0 28 28
PIP5K1C 0.037 0.012 -10000 0 0 51 51
regulation of heterotypic cell-cell adhesion 0.045 0.073 0.22 2 -0.12 60 62
E-cadherin/beta catenin 0.007 0.04 0.14 1 -0.23 12 13
mol:GTP 0 0 -10000 0 -10000 0 0
SRC -0.031 0.14 -10000 0 -0.34 77 77
PIK3CA 0.029 0.019 -10000 0 0 166 166
Rac1/GTP -0.056 0.13 -10000 0 -0.35 66 66
E-cadherin/beta catenin/alpha catenin 0.055 0.062 -10000 0 -0.13 45 45
ITGAE 0.038 0.011 -10000 0 0 41 41
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin -0.02 0.15 -10000 0 -0.35 78 78
E-cadherin signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin 0.052 0.063 -9999 0 -0.12 47 47
E-cadherin/beta catenin 0.041 0.049 -9999 0 -0.14 33 33
CTNNB1 0.039 0.01 -9999 0 0 32 32
JUP 0.037 0.013 -9999 0 0 57 57
CDH1 0.035 0.014 -9999 0 0 79 79
Caspase cascade in apoptosis

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
TOP1 -0.011 0.14 0.28 2 -0.3 65 67
ACTA1 0.005 0.085 0.2 14 -0.23 21 35
NUMA1 -0.014 0.13 0.25 3 -0.3 71 74
SPTAN1 -0.002 0.083 0.19 11 -0.23 20 31
LIMK1 0.002 0.084 0.2 13 -0.23 21 34
BIRC3 0.025 0.02 -10000 0 0 210 210
BIRC2 0.036 0.014 -10000 0 0 72 72
BAX 0.039 0.008 -10000 0 0 23 23
CASP10 -0.011 0.025 0.059 54 -10000 0 54
CRMA 0 0 -10000 0 -10000 0 0
XIAP 0 0 -10000 0 -10000 0 0
PTK2 -0.031 0.17 0.28 2 -0.38 70 72
DIABLO 0.037 0.013 -10000 0 0 61 61
apoptotic nuclear changes -0.002 0.082 0.19 11 -0.23 20 31
response to UV 0 0 -10000 0 -10000 0 0
CRADD 0.04 0.006 -10000 0 0 10 10
GSN -0.002 0.083 0.2 12 -0.24 20 32
MADD 0.041 0.005 -10000 0 0 9 9
TFAP2A -0.028 0.2 -10000 0 -0.56 51 51
BID 0.002 0.022 -10000 0 -0.094 22 22
MAP3K1 -0.018 0.13 -10000 0 -0.37 56 56
TRADD 0.037 0.013 -10000 0 0 61 61
mol:Ca2+ 0 0 -10000 0 -10000 0 0
APAF-1/Pro-Caspase 9 0.051 0.039 -10000 0 -0.14 18 18
mol:Activated DNA 0 0 -10000 0 -10000 0 0
ARHGDIB 0.007 0.1 0.23 42 -0.22 33 75
CASP9 0.039 0.008 -10000 0 0 24 24
DNA repair -0.012 0.08 0.27 23 -0.16 11 34
neuron apoptosis -0.03 0.19 -10000 0 -0.63 43 43
mol:NAD 0 0 -10000 0 -10000 0 0
DNA fragmentation during apoptosis -0.013 0.12 0.23 6 -0.3 45 51
APAF1 0.039 0.009 -10000 0 0 28 28
CASP6 -0.094 0.33 -10000 0 -0.86 80 80
TRAF2 0.039 0.01 -10000 0 0 32 32
ICAD/CAD -0.002 0.079 0.2 11 -0.22 18 29
CASP7 0.016 0.097 0.18 79 -0.25 17 96
KRT18 -0.012 0.14 -10000 0 -0.57 22 22
apoptosis -0.036 0.16 0.29 11 -0.37 77 88
DFFA 0.002 0.081 0.2 11 -0.22 19 30
DFFB 0.002 0.082 0.2 11 -0.23 20 31
PARP1 0.012 0.08 0.16 11 -0.28 23 34
actin filament polymerization 0.003 0.081 0.23 18 -0.23 10 28
TNF 0.04 0.008 -10000 0 0 22 22
CYCS -0.001 0.067 0.15 9 -0.21 31 40
SATB1 -0.097 0.31 -10000 0 -0.82 79 79
SLK -0.001 0.085 0.22 9 -0.23 22 31
p15 BID/BAX 0.025 0.058 0.18 2 -0.13 38 40
CASP2 0 0.091 0.23 18 -0.24 35 53
JNK cascade 0.018 0.13 0.37 56 -10000 0 56
CASP3 0.007 0.087 0.18 26 -0.21 27 53
LMNB2 -0.047 0.21 0.24 2 -0.41 102 104
RIPK1 0.039 0.01 -10000 0 0 32 32
CASP4 0.033 0.016 -10000 0 0 107 107
Mammalian IAPs/DIABLO 0.011 0.088 -10000 0 -0.13 129 129
negative regulation of DNA binding -0.027 0.19 -10000 0 -0.55 51 51
stress fiber formation -0.001 0.084 0.22 9 -0.22 22 31
GZMB -0.016 0.009 0 125 -10000 0 125
CASP1 -0.012 0.069 -10000 0 -0.2 66 66
LMNB1 -0.046 0.19 0.25 4 -0.35 115 119
APP -0.031 0.2 -10000 0 -0.64 43 43
TNFRSF1A 0.036 0.014 -10000 0 0 72 72
response to stress 0 0 -10000 0 -10000 0 0
CASP8 -0.01 0.002 0 27 -10000 0 27
VIM -0.03 0.16 0.29 11 -0.36 81 92
LMNA -0.018 0.15 0.29 1 -0.37 58 59
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD 0.002 0.086 -10000 0 -0.24 39 39
LRDD 0.039 0.01 -10000 0 0 36 36
SREBF1 0.002 0.082 0.2 10 -0.23 21 31
APAF-1/Caspase 9 0.027 0.16 -10000 0 -0.69 20 20
nuclear fragmentation during apoptosis -0.013 0.13 0.25 3 -0.29 71 74
CFL2 -0.003 0.081 0.23 10 -0.23 18 28
GAS2 0.004 0.086 0.21 17 -0.23 21 38
positive regulation of apoptosis -0.04 0.18 0.24 3 -0.4 88 91
PRF1 0.037 0.013 -10000 0 0 61 61
Signaling events mediated by PRL

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CCNE1 0.026 0.02 -10000 0 0 202 202
mol:Halofuginone 0.002 0.022 -10000 0 -0.17 9 9
ITGA1 0.032 0.017 -10000 0 0 121 121
CDKN1A 0.021 0.077 -10000 0 -0.35 16 16
PRL-3/alpha Tubulin 0.011 0.038 -10000 0 -0.12 35 35
mol:Ca2+ -0.004 0.072 0.26 35 -10000 0 35
AGT 0.039 0.01 -10000 0 0 35 35
CCNA2 -0.015 0.09 -10000 0 -0.61 7 7
TUBA1B 0 0 -10000 0 -10000 0 0
EGR1 0.006 0.043 -10000 0 -0.32 9 9
CDK2/Cyclin E1 0.023 0.092 -10000 0 -0.36 16 16
MAPK3 -0.012 0.01 0 221 -10000 0 221
PRL-2 /Rab GGTase beta 0.032 0.067 -10000 0 -0.14 70 70
MAPK1 -0.012 0.01 -10000 0 -10000 0 0
PTP4A1 -0.004 0.074 -10000 0 -0.61 7 7
PTP4A3 0.025 0.02 -10000 0 0 209 209
PTP4A2 0.039 0.009 -10000 0 0 30 30
ITGB1 -0.012 0.01 -10000 0 -10000 0 0
SRC 0.039 0.009 -10000 0 0 28 28
RAC1 -0.006 0.11 -10000 0 -0.36 42 42
Rab GGTase beta/Rab GGTase alpha 0.035 0.062 -10000 0 -0.13 62 62
PRL-1/ATF-5 0.017 0.097 0.26 2 -0.54 9 11
RABGGTA 0.04 0.007 -10000 0 0 17 17
BCAR1 -0.005 0.066 0.26 29 -10000 0 29
RHOC -0.005 0.11 -10000 0 -0.37 40 40
RHOA -0.006 0.11 -10000 0 -0.36 42 42
cell motility 0.008 0.12 -10000 0 -0.34 43 43
PRL-1/alpha Tubulin -0.017 0.078 -10000 0 -0.53 9 9
PRL-3/alpha1 Integrin 0.01 0.067 -10000 0 -0.14 69 69
ROCK1 0.008 0.12 -10000 0 -0.34 42 42
RABGGTB 0.035 0.014 -10000 0 0 79 79
CDK2 0.037 0.013 -10000 0 0 56 56
mitosis -0.001 0.077 0.2 6 -0.6 7 13
ATF5 0.038 0.011 -10000 0 0 41 41
Presenilin action in Notch and Wnt signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved) 0.022 0.14 -10000 0 -0.43 44 44
HDAC1 0.043 0.024 0.083 111 -0.003 54 165
AES 0.038 0.016 0.078 17 0 69 86
FBXW11 0.04 0.008 -10000 0 0 22 22
DTX1 0.041 0.005 -10000 0 0 9 9
LRP6/FZD1 0.042 0.048 -10000 0 -0.13 32 32
TLE1 0.039 0.014 0.076 14 -0.001 51 65
AP1 -0.007 0.082 0.14 2 -0.18 87 89
NCSTN 0.039 0.008 -10000 0 0 22 22
ADAM10 0.039 0.01 -10000 0 0 31 31
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4 -0.074 0.22 -10000 0 -0.65 49 49
NICD/RBPSUH -0.006 0.13 -10000 0 -0.44 43 43
WIF1 0.039 0.009 -10000 0 0 26 26
NOTCH1 0.006 0.13 -10000 0 -0.46 39 39
PSENEN 0.034 0.016 -10000 0 0 96 96
KREMEN2 0.039 0.009 -10000 0 0 29 29
DKK1 0.038 0.011 -10000 0 0 39 39
beta catenin/beta TrCP1 0.015 0.093 0.23 1 -0.3 19 20
APH1B 0.035 0.014 -10000 0 0 79 79
APH1A 0.038 0.011 -10000 0 0 42 42
AXIN1 -0.016 0.12 0.23 1 -0.45 28 29
CtBP/CBP/TCF1/TLE1/AES 0.009 0.099 0.18 82 -0.18 51 133
PSEN1 0.039 0.01 -10000 0 0 31 31
FOS 0.026 0.02 -10000 0 0 201 201
JUN 0.035 0.014 -10000 0 0 76 76
MAP3K7 0.041 0.014 0.068 14 0 38 52
CTNNB1 -0.001 0.086 0.22 1 -0.31 17 18
MAPK3 0.04 0.007 -10000 0 0 18 18
DKK2/LRP6/Kremen 2 0.057 0.053 -10000 0 -0.12 29 29
HNF1A 0.002 0.008 0.037 18 -10000 0 18
CTBP1 0.04 0.015 0.078 19 0 49 68
MYC -0.15 0.41 -10000 0 -1.2 69 69
NKD1 0.039 0.012 -10000 0 0 43 43
FZD1 0.04 0.006 -10000 0 0 13 13
NOTCH1 precursor/Deltex homolog 1 0.024 0.15 -10000 0 -0.43 45 45
apoptosis -0.007 0.082 0.14 2 -0.18 87 89
Delta 1/NOTCHprecursor 0.019 0.14 -10000 0 -0.42 46 46
DLL1 0.037 0.013 -10000 0 0 61 61
PPARD 0.009 0.069 -10000 0 -0.87 2 2
Gamma Secretase 0.066 0.084 -10000 0 -0.12 63 63
APC -0.015 0.12 0.23 1 -0.46 28 29
DVL1 0.012 0.068 -10000 0 -0.26 24 24
CSNK2A1 0.037 0.012 -10000 0 0 47 47
MAP3K7IP1 0.04 0.015 0.068 15 0 51 66
DKK1/LRP6/Kremen 2 0.056 0.052 -10000 0 -0.12 28 28
LRP6 0.034 0.016 -10000 0 0 94 94
CSNK1A1 0.039 0.008 -10000 0 0 23 23
NLK 0.026 0.042 -10000 0 -0.22 11 11
CCND1 -0.16 0.44 -10000 0 -1.2 81 81
WNT1 0.04 0.006 -10000 0 0 10 10
Axin1/APC/beta catenin -0.002 0.12 0.27 2 -0.37 26 28
DKK2 0.039 0.01 -10000 0 0 33 33
NOTCH1 precursor/DVL1 0.013 0.15 -10000 0 -0.43 44 44
GSK3B 0.04 0.009 -10000 0 0 23 23
FRAT1 0.041 0.008 -10000 0 0 17 17
NOTCH/Deltex homolog 1 0.027 0.15 -10000 0 -0.44 44 44
PPP2R5D 0.017 0.066 -10000 0 -0.4 10 10
MAPK1 0.038 0.011 -10000 0 0 44 44
WNT1/LRP6/FZD1 0.076 0.059 -10000 0 -0.11 31 31
RBPJ 0 0 -10000 0 -10000 0 0
CREBBP 0.029 0.024 -10000 0 -0.017 85 85
IL2 signaling events mediated by PI3K

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BCL2L1 -0.012 0.16 -10000 0 -0.7 18 18
UGCG -0.003 0.13 -10000 0 -0.67 18 18
AKT1/mTOR/p70S6K/Hsp90/TERT -0.021 0.18 0.27 2 -0.38 76 78
mol:GTP 0 0.001 -10000 0 -10000 0 0
mol:glucosylceramide -0.002 0.13 -10000 0 -0.66 18 18
mol:DAG -0.008 0.028 0.17 12 -10000 0 12
CaM/Ca2+/Calcineurin A alpha-beta B1 -0.036 0.22 0.28 1 -0.48 81 82
FRAP1 -0.055 0.26 0.29 3 -0.57 81 84
FOXO3 -0.052 0.25 0.26 2 -0.53 90 92
AKT1 -0.06 0.28 0.27 2 -0.58 90 92
GAB2 0.029 0.02 -10000 0 -0.003 149 149
SMPD1 0.002 0.12 -10000 0 -0.61 16 16
SGMS1 -0.003 0.038 0.059 12 -0.079 75 87
positive regulation of NF-kappaB transcription factor activity 0 0 -10000 0 -10000 0 0
mol:Ca2+ 0 0 -10000 0 -10000 0 0
mol:GDP -0.019 0.034 -10000 0 -0.12 50 50
CALM1 0.039 0.009 -10000 0 0 26 26
cell proliferation 0.005 0.16 0.23 14 -0.31 73 87
EIF3A 0 0 -10000 0 -10000 0 0
PI3K 0.02 0.062 -10000 0 -0.14 52 52
RPS6KB1 -0.022 0.2 -10000 0 -0.88 25 25
mol:sphingomyelin -0.008 0.028 0.17 12 -10000 0 12
natural killer cell activation -0.001 0.004 -10000 0 -0.014 24 24
JAK3 0.034 0.022 -10000 0 -0.046 24 24
PIK3R1 0.031 0.024 -10000 0 -0.041 26 26
JAK1 0.036 0.021 -10000 0 -0.043 24 24
NFKB1 0.036 0.013 -10000 0 0 66 66
MYC -0.035 0.34 0.37 18 -0.8 76 94
MYB -0.047 0.29 -10000 0 -1.1 39 39
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K -0.024 0.17 0.27 2 -0.37 78 80
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3 -0.004 0.19 -10000 0 -0.81 25 25
mol:PI-3-4-5-P3 -0.024 0.17 0.27 2 -0.37 78 80
Rac1/GDP 0.008 0.044 -10000 0 -0.11 46 46
T cell proliferation -0.027 0.16 0.28 6 -0.35 78 84
SHC1 0.037 0.016 -10000 0 -0.015 43 43
RAC1 0.039 0.009 -10000 0 0 28 28
positive regulation of cyclin-dependent protein kinase activity 0.001 0.019 0.031 39 -0.064 39 78
PRKCZ -0.027 0.16 0.28 6 -0.36 77 83
NF kappa B1 p50/RelA -0.026 0.24 0.3 2 -0.49 81 83
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K -0.005 0.12 -10000 0 -0.34 39 39
HSP90AA1 0 0 -10000 0 -10000 0 0
RELA 0.04 0.006 -10000 0 0 10 10
IL2RA 0.036 0.017 -10000 0 -0.011 58 58
IL2RB 0.033 0.022 -10000 0 -0.046 20 20
TERT 0.037 0.012 -10000 0 0 53 53
E2F1 -0.006 0.12 -10000 0 -0.41 40 40
SOS1 0.035 0.018 -10000 0 -0.009 71 71
RPS6 0.039 0.01 -10000 0 0 32 32
mol:cAMP -0.001 0.009 0.031 36 -0.016 39 75
PTPN11 0.035 0.02 -10000 0 -0.018 64 64
IL2RG 0.025 0.026 -10000 0 -0.041 28 28
actin cytoskeleton organization -0.027 0.16 0.28 6 -0.35 78 84
GRB2 0.037 0.016 -10000 0 -0.015 41 41
IL2 0.035 0.024 -10000 0 -0.04 38 38
PIK3CA 0.027 0.024 -10000 0 -0.042 21 21
Rac1/GTP 0.029 0.061 -10000 0 -0.11 42 42
LCK 0.035 0.024 -10000 0 -0.039 41 41
BCL2 -0.029 0.2 0.38 1 -0.53 48 49
Class I PI3K signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
ARF5/GTP -0.013 0.071 0.15 75 -0.18 5 80
DAPP1 -0.006 0.1 0.2 9 -0.24 51 60
Src family/SYK family/BLNK-LAT/BTK-ITK -0.015 0.14 -10000 0 -0.35 53 53
mol:DAG 0.002 0.075 0.17 21 -0.17 30 51
HRAS 0.04 0.013 0.076 3 -0.004 35 38
RAP1A 0.04 0.012 0.068 4 -0.001 36 40
ARF5/GDP 0.011 0.1 -10000 0 -0.24 42 42
PLCG2 0.035 0.015 -10000 0 0 82 82
PLCG1 0.038 0.011 -10000 0 0 43 43
ARF5 0.038 0.01 -10000 0 0 36 36
mol:GTP -0.014 0.064 0.14 71 -0.18 4 75
ARF1/GTP 0.001 0.063 0.14 80 -0.16 4 84
RHOA 0.04 0.006 -10000 0 0 13 13
YES1 0.037 0.012 -10000 0 0 51 51
RAP1A/GTP -0.006 0.074 0.16 77 -0.18 4 81
ADAP1 -0.015 0.059 0.13 68 -0.17 4 72
ARAP3 -0.014 0.064 0.14 71 -0.18 4 75
INPPL1 0.039 0.009 -10000 0 0 27 27
PREX1 0.038 0.012 -10000 0 0 48 48
ARHGEF6 0.036 0.013 -10000 0 0 64 64
ARHGEF7 0.039 0.009 -10000 0 0 28 28
ARF1 0.038 0.011 -10000 0 0 45 45
NRAS 0.041 0.011 0.069 3 0 30 33
FYN 0.034 0.016 -10000 0 0 94 94
ARF6 0.04 0.007 -10000 0 0 16 16
FGR 0.04 0.007 -10000 0 0 15 15
mol:Ca2+ -0.001 0.049 0.17 14 -0.11 9 23
mol:IP4 0 0 -10000 0 -10000 0 0
TIAM1 0.036 0.013 -10000 0 0 66 66
ZAP70 0.041 0.005 -10000 0 0 9 9
mol:IP3 -0.004 0.062 0.21 14 -0.15 13 27
LYN 0.035 0.015 -10000 0 0 83 83
ARF1/GDP 0.014 0.097 -10000 0 -0.24 37 37
RhoA/GDP 0.032 0.084 0.19 46 -0.17 26 72
PDK1/Src/Hsp90 0.049 0.023 -10000 0 -0.11 6 6
BLNK 0.037 0.013 -10000 0 0 62 62
actin cytoskeleton reorganization 0.002 0.094 0.22 9 -0.26 24 33
SRC 0.039 0.009 -10000 0 0 28 28
PLEKHA2 -0.014 0.006 -10000 0 -10000 0 0
RAC1 0.039 0.009 -10000 0 0 28 28
PTEN 0.032 0.026 -10000 0 -0.03 71 71
HSP90AA1 0 0 -10000 0 -10000 0 0
ARF6/GTP -0.013 0.073 0.15 77 -0.18 4 81
RhoA/GTP -0.01 0.077 0.16 81 -0.18 5 86
Src family/SYK family/BLNK-LAT -0.003 0.097 -10000 0 -0.27 37 37
BLK 0.033 0.017 -10000 0 0 114 114
PDPK1 0.039 0.009 -10000 0 0 29 29
CYTH1 -0.015 0.059 0.13 68 -0.17 4 72
HCK 0.036 0.013 -10000 0 0 65 65
CYTH3 -0.015 0.059 0.13 68 -0.17 4 72
CYTH2 -0.015 0.059 0.13 68 -0.17 4 72
KRAS 0.034 0.017 0.09 1 -0.001 98 99
GO:0030676 0 0 -10000 0 -10000 0 0
FOXO3 0.008 0.047 0.2 1 -0.16 15 16
SGK1 0.008 0.046 -10000 0 -0.17 15 15
INPP5D 0 0 -10000 0 -10000 0 0
mol:GDP -0.005 0.095 -10000 0 -0.25 41 41
SOS1 0.037 0.012 -10000 0 0 51 51
SYK 0.036 0.014 -10000 0 0 67 67
ARF6/GDP -0.003 0.079 0.16 57 -0.18 18 75
mol:PI-3-4-5-P3 -0.015 0.063 0.14 68 -0.18 4 72
ARAP3/RAP1A/GTP -0.006 0.074 0.16 77 -0.18 4 81
VAV1 0.036 0.014 -10000 0 0 69 69
mol:PI-3-4-P2 -0.01 0.002 -10000 0 -10000 0 0
RAS family/GTP/PI3K Class I 0.042 0.063 0.22 23 -0.12 38 61
PLEKHA1 -0.015 0.005 -10000 0 -10000 0 0
Rac1/GDP 0.014 0.1 -10000 0 -0.24 42 42
LAT 0.04 0.006 -10000 0 0 11 11
Rac1/GTP -0.006 0.099 -10000 0 -0.26 50 50
ITK -0.014 0.064 0.13 73 -0.18 5 78
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma -0.003 0.093 0.2 16 -0.22 34 50
LCK 0.039 0.009 -10000 0 0 25 25
BTK -0.016 0.067 0.14 70 -0.18 9 79
EPO signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BCL2L1 0.027 0.14 0.35 3 -0.5 23 26
CRKL 0.025 0.086 0.18 114 -0.15 1 115
mol:DAG 0.042 0.074 0.21 5 -0.23 17 22
HRAS 0.023 0.1 0.27 43 -0.18 3 46
MAPK8 0.014 0.083 0.19 83 -0.14 2 85
RAP1A 0.024 0.086 0.18 111 -0.17 3 114
GAB1 0.022 0.083 0.18 105 -0.15 1 106
MAPK14 0.016 0.086 0.19 88 -0.14 2 90
EPO 0.045 0.015 0.081 8 -0.037 7 15
PLCG1 0.042 0.075 0.21 5 -0.23 17 22
EPOR/TRPC2/IP3 Receptors 0.039 0.019 0.082 2 -0.037 6 8
RAPGEF1 0.039 0.009 -10000 0 0 26 26
EPO/EPOR (dimer)/SOCS3 0.063 0.051 -10000 0 -0.13 16 16
GAB1/SHC/GRB2/SOS1 0.067 0.081 0.24 28 -0.17 4 32
EPO/EPOR (dimer) 0.056 0.032 -10000 0 -0.14 2 2
IRS2 0.024 0.085 0.18 111 -0.15 1 112
STAT1 0.038 0.09 0.23 5 -0.24 31 36
STAT5B 0.046 0.079 0.22 6 -0.21 24 30
cell proliferation 0.007 0.081 0.18 83 -0.13 1 84
GAB1/SHIP/PIK3R1/SHP2/SHC 0.032 0.061 0.16 4 -0.16 6 10
TEC 0.019 0.081 0.18 97 -0.17 9 106
SOCS3 0.036 0.013 -10000 0 0 63 63
STAT1 (dimer) 0.038 0.089 0.23 5 -0.24 31 36
JAK2 0.037 0.02 0.081 6 -0.035 4 10
PIK3R1 0.034 0.016 -10000 0 0 99 99
EPO/EPOR (dimer)/JAK2 0.063 0.068 0.24 24 -0.1 30 54
EPO/EPOR 0.056 0.032 -10000 0 -0.14 2 2
LYN 0.035 0.018 -10000 0 -0.036 9 9
TEC/VAV2 0.032 0.076 0.22 22 -0.16 12 34
elevation of cytosolic calcium ion concentration 0.039 0.019 0.082 2 -0.036 6 8
SHC1 0.039 0.008 -10000 0 0 23 23
EPO/EPOR (dimer)/LYN 0.06 0.061 -10000 0 -0.12 28 28
mol:IP3 0.042 0.074 0.21 5 -0.23 17 22
PI3K regualtory subunit polypeptide 1/IRS2/SHIP 0.045 0.074 0.18 82 -0.13 5 87
SH2B3 -0.001 0.007 0.031 10 -10000 0 10
NFKB1 0.013 0.082 0.19 75 -0.18 5 80
EPO/EPOR (dimer)/JAK2/SOCS3 0.011 0.052 -10000 0 -0.16 36 36
PTPN6 0.035 0.067 0.18 76 -0.1 28 104
TEC/VAV2/GRB2 0.049 0.084 0.23 27 -0.17 10 37
EPOR 0.039 0.019 0.082 2 -0.037 6 8
INPP5D 0 0 -10000 0 -10000 0 0
mol:GDP 0.066 0.081 0.24 28 -0.17 4 32
SOS1 0.037 0.012 -10000 0 0 51 51
PLCG2 0.035 0.015 -10000 0 0 82 82
CRKL/CBL/C3G 0.071 0.076 0.24 37 -0.15 3 40
VAV2 0.021 0.083 0.18 103 -0.16 2 105
CBL 0.025 0.088 0.18 117 -0.22 1 118
SHC/Grb2/SOS1 0.036 0.056 0.17 2 -0.13 11 13
STAT5A 0.045 0.081 0.22 6 -0.22 25 31
GRB2 0.04 0.008 -10000 0 0 21 21
STAT5 (dimer) 0.062 0.093 0.28 4 -0.28 15 19
LYN/PLCgamma2 0.037 0.049 -10000 0 -0.13 32 32
PTPN11 0.039 0.009 -10000 0 0 29 29
BTK 0.023 0.087 0.18 110 -0.17 7 117
BCL2 0.03 0.12 0.34 3 -0.42 15 18
Circadian rhythm pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
chromatin modification -0.048 0.3 -10000 0 -1 47 47
CLOCK 0.031 0.031 -10000 0 -0.069 40 40
TIMELESS/CRY2 -0.049 0.31 -10000 0 -1 47 47
DEC1/BMAL1 0.044 0.047 -10000 0 -0.13 19 19
ATR 0.035 0.015 -10000 0 0 84 84
NR1D1 -0.013 0.11 -10000 0 -0.63 1 1
ARNTL 0.032 0.031 -10000 0 -0.068 42 42
TIMELESS -0.08 0.32 -10000 0 -1.1 47 47
NPAS2 0.027 0.031 -10000 0 -0.067 36 36
CRY2 0.041 0.004 -10000 0 0 5 5
mol:CO 0.001 0.04 0.13 47 -10000 0 47
CHEK1 0.032 0.017 -10000 0 0 118 118
mol:HEME -0.001 0.04 -10000 0 -0.13 47 47
PER1 0.038 0.011 -10000 0 0 44 44
BMAL/CLOCK/NPAS2 0.029 0.095 -10000 0 -0.13 112 112
BMAL1/CLOCK -0.037 0.2 -10000 0 -0.58 49 49
S phase of mitotic cell cycle -0.048 0.3 -10000 0 -1 47 47
TIMELESS/CHEK1/ATR -0.05 0.31 -10000 0 -1 47 47
mol:NADPH -0.001 0.04 -10000 0 -0.13 47 47
PER1/TIMELESS -0.052 0.31 -10000 0 -1 47 47
PER1-2 / CRY1-2 0 0 -10000 0 -10000 0 0
DEC1 0.04 0.008 -10000 0 0 19 19
HIV-1 Nef: Negative effector of Fas and TNF-alpha

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BAG4 0.037 0.012 -10000 0 0 55 55
Caspase 8 (4 units) 0.037 0.092 -10000 0 -0.24 27 27
NEF 0.003 0.005 -10000 0 -0.1 1 1
NFKBIA 0.025 0.043 0.084 9 -0.068 79 88
BIRC3 -0.059 0.1 0.18 5 -0.28 89 94
CYCS -0.004 0.062 0.18 7 -0.26 13 20
RIPK1 0.039 0.01 -10000 0 0 32 32
CD247 0.003 0.005 -10000 0 -0.1 1 1
MAP2K7 -0.006 0.17 -10000 0 -0.56 34 34
protein ubiquitination -0.002 0.098 0.2 5 -0.26 38 43
CRADD 0.04 0.006 -10000 0 0 10 10
DAXX 0.04 0.006 -10000 0 0 11 11
FAS 0.035 0.015 -10000 0 0 88 88
BID 0.005 0.06 0.18 3 -0.26 12 15
NF-kappa-B/RelA/I kappa B alpha 0.027 0.11 -10000 0 -0.17 117 117
TRADD 0.037 0.013 -10000 0 0 61 61
MAP3K5 0.037 0.013 -10000 0 0 60 60
CFLAR 0.04 0.008 -10000 0 0 19 19
FADD 0.04 0.008 -10000 0 0 20 20
NF-kappa-B/RelA/I kappa B alpha/ubiquitin 0.027 0.11 -10000 0 -0.18 117 117
MAPK8 -0.01 0.16 -10000 0 -0.54 32 32
APAF1 0.039 0.009 -10000 0 0 28 28
TRAF1 0.04 0.007 -10000 0 0 17 17
TRAF2 0.039 0.01 -10000 0 0 32 32
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG 0.013 0.067 -10000 0 -0.27 14 14
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD 0.006 0.12 0.21 1 -0.32 37 38
CHUK -0.003 0.1 0.21 4 -0.28 39 43
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8 0.077 0.083 -10000 0 -0.12 56 56
TCRz/NEF 0.01 0.008 -10000 0 -0.17 1 1
TNF 0.04 0.008 -10000 0 0 22 22
FASLG 0.022 0.014 -10000 0 -0.29 1 1
NFKB1 0.027 0.041 0.095 2 -0.07 68 70
TNFR1A/BAG4/TNF-alpha 0.06 0.045 -10000 0 -0.11 15 15
CASP6 -0.039 0.23 -10000 0 -0.53 84 84
CASP7 -0.042 0.2 0.27 9 -0.41 103 112
RELA 0.027 0.045 0.082 9 -0.066 96 105
CASP2 0.038 0.011 -10000 0 0 41 41
CASP3 -0.054 0.2 0.28 8 -0.41 111 119
TNFRSF1A 0.036 0.014 -10000 0 0 72 72
TNFR1A/BAG4 0.045 0.037 -10000 0 -0.13 14 14
CASP8 0.039 0.009 -10000 0 0 27 27
CASP9 0.039 0.008 -10000 0 0 24 24
MAP3K14 0.003 0.11 0.2 5 -0.3 36 41
APAF-1/Caspase 9 -0.025 0.11 0.19 1 -0.24 92 93
BCL2 -0.009 0.14 -10000 0 -0.49 32 32
Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
adherens junction organization 0.005 0.067 -10000 0 -0.19 48 48
epithelial cell differentiation 0.058 0.066 -10000 0 -0.12 48 48
CYFIP2 0.038 0.011 -10000 0 0 45 45
ENAH -0.036 0.067 0.19 11 -0.2 7 18
EGFR 0.036 0.014 -10000 0 0 67 67
EPHA2 0.039 0.009 -10000 0 0 26 26
MYO6 -0.029 0.048 0.18 9 -0.2 16 25
CTNNB1 0.039 0.01 -10000 0 0 32 32
ABI1/Sra1/Nap1 0.061 0.057 -10000 0 -0.12 39 39
AQP5 -0.069 0.14 -10000 0 -0.37 88 88
CTNND1 0.04 0.007 -10000 0 0 17 17
mol:PI-4-5-P2 -0.029 0.044 0.18 9 -0.19 12 21
regulation of calcium-dependent cell-cell adhesion -0.029 0.041 0.17 6 -0.19 12 18
EGF 0.038 0.01 -10000 0 0 38 38
NCKAP1 0.039 0.009 -10000 0 0 26 26
AQP3 -0.018 0.048 -10000 0 -0.28 8 8
cortical microtubule organization 0.058 0.066 -10000 0 -0.12 48 48
GO:0000145 -0.028 0.04 0.16 9 -0.18 12 21
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin 0.065 0.069 -10000 0 -0.12 48 48
MLLT4 0.033 0.016 -10000 0 0 109 109
ARF6/GDP -0.052 0.047 -10000 0 -0.19 28 28
ARF6 0.04 0.007 -10000 0 0 16 16
Ephrin A1/EPHA2/NCK1/GIT1 0.06 0.078 -10000 0 -0.12 66 66
mol:Ca2+ 0 0 -10000 0 -10000 0 0
VASP -0.015 0.046 0.17 6 -0.19 15 21
PVRL2 0.037 0.012 -10000 0 0 51 51
ZYX -0.026 0.042 0.18 9 -0.19 8 17
ARF6/GTP 0.065 0.084 -10000 0 -0.12 68 68
CDH1 0.035 0.014 -10000 0 0 79 79
EGFR/EGFR/EGF/EGF 0.039 0.073 -10000 0 -0.12 72 72
RhoA/GDP 0.058 0.068 -10000 0 -0.12 52 52
actin cytoskeleton organization -0.031 0.048 0.16 9 -0.21 17 26
IGF-1R heterotetramer 0.033 0.017 -10000 0 0 112 112
GIT1 0.039 0.009 -10000 0 0 25 25
IGF1R 0.033 0.017 -10000 0 0 112 112
IGF1 0.035 0.014 -10000 0 0 77 77
DIAPH1 -0.003 0.22 -10000 0 -0.56 71 71
Wnt receptor signaling pathway -0.058 0.066 0.12 48 -10000 0 48
RHOA 0.04 0.006 -10000 0 0 13 13
RhoA/GTP -0.051 0.046 -10000 0 -0.18 28 28
CTNNA1 0.039 0.01 -10000 0 0 31 31
VCL -0.031 0.049 0.16 9 -0.22 17 26
EFNA1 0.034 0.016 -10000 0 0 96 96
LPP -0.029 0.044 0.16 8 -0.19 13 21
Ephrin A1/EPHA2 0.035 0.075 -10000 0 -0.12 77 77
SEC6/SEC8 -0.04 0.041 -10000 0 -0.18 18 18
MGAT3 -0.029 0.042 0.18 6 -0.19 12 18
HGF/MET 0.019 0.084 -10000 0 -0.12 110 110
HGF 0.039 0.009 -10000 0 0 27 27
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN 0.005 0.068 -10000 0 -0.19 48 48
actin cable formation 0 0.094 0.25 22 -0.23 23 45
KIAA1543 -0.033 0.042 0.16 8 -0.2 12 20
KIFC3 -0.031 0.044 0.18 9 -0.19 12 21
NCK1 0.036 0.014 -10000 0 0 70 70
EXOC3 0.037 0.012 -10000 0 0 55 55
ACTN1 -0.03 0.048 0.18 10 -0.2 15 25
NCK1/GIT1 0.043 0.047 -10000 0 -0.13 31 31
mol:GDP 0.058 0.066 -10000 0 -0.12 48 48
EXOC4 0.038 0.011 -10000 0 0 41 41
STX4 -0.029 0.032 0.038 7 -0.12 46 53
PIP5K1C -0.029 0.044 0.18 9 -0.19 12 21
LIMA1 0 0 -10000 0 -10000 0 0
ABI1 0.039 0.009 -10000 0 0 28 28
ROCK1 -0.03 0.08 0.22 12 -0.23 6 18
adherens junction assembly -0.043 0.12 -10000 0 -0.38 36 36
IGF-1R heterotetramer/IGF1 0.025 0.08 -10000 0 -0.12 95 95
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin 0.038 0.047 -10000 0 -0.14 27 27
MET 0.027 0.02 -10000 0 0 191 191
PLEKHA7 -0.03 0.046 0.18 10 -0.2 13 23
mol:GTP 0.057 0.076 -10000 0 -0.12 66 66
establishment of epithelial cell apical/basal polarity -0.02 0.074 0.15 66 -0.2 13 79
cortical actin cytoskeleton stabilization 0.005 0.067 -10000 0 -0.19 48 48
regulation of cell-cell adhesion -0.031 0.048 0.16 9 -0.21 17 26
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton 0.005 0.068 -10000 0 -0.19 48 48
Aurora B signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
Condensin I complex -0.009 0.038 -10000 0 -0.11 62 62
STMN1 -0.012 0.014 0.024 15 -10000 0 15
Aurora B/RasGAP/Survivin 0.047 0.072 -10000 0 -0.15 49 49
Chromosomal passenger complex/Cul3 protein complex -0.006 0.089 -10000 0 -0.24 44 44
BIRC5 0.037 0.014 -10000 0 -0.003 56 56
DES -0.051 0.28 -10000 0 -0.8 63 63
Aurora C/Aurora B/INCENP 0.059 0.047 -10000 0 -0.11 26 26
Aurora B/TACC1 0.037 0.038 -10000 0 -0.11 22 22
Aurora B/PP2A 0.044 0.048 -10000 0 -0.14 29 29
mol:GTP 0 0 -10000 0 -10000 0 0
CBX5 -0.011 0.061 -10000 0 -0.16 72 72
mitotic metaphase/anaphase transition 0.002 0.006 0.013 109 -10000 0 109
NDC80 -0.005 0.009 0.019 11 -10000 0 11
Cul3 protein complex 0.049 0.06 -10000 0 -0.12 45 45
KIF2C -0.058 0.19 -10000 0 -0.49 78 78
PEBP1 -0.001 0.003 -10000 0 -0.011 38 38
KIF20A 0.032 0.018 -10000 0 0 125 125
mol:GDP 0 0 -10000 0 -10000 0 0
Aurora B/RasGAP 0.037 0.055 -10000 0 -0.14 43 43
SEPT1 0.04 0.007 -10000 0 0 17 17
SMC2 0 0 -10000 0 -10000 0 0
SMC4 0 0 -10000 0 -10000 0 0
NSUN2/NPM1/Nucleolin -0.045 0.2 0.27 1 -0.56 63 64
PSMA3 0.037 0.012 -10000 0 0 51 51
G2/M transition of mitotic cell cycle -0.001 0.003 0.009 36 -0.008 17 53
H3F3B 0.002 0.056 -10000 0 -0.2 38 38
AURKB 0.037 0.016 0.066 1 0 79 80
AURKC 0.039 0.01 -10000 0 0 34 34
CDCA8 0.036 0.015 -10000 0 -0.005 58 58
cytokinesis -0.032 0.18 -10000 0 -0.46 64 64
Aurora B/Septin1 -0.009 0.19 -10000 0 -0.45 61 61
AURKA -0.001 0.003 0.009 36 -0.008 17 53
INCENP 0.038 0.015 -10000 0 -0.029 26 26
KLHL13 0.032 0.017 -10000 0 0 117 117
BUB1 0.037 0.015 -10000 0 0 72 72
hSgo1/Aurora B/Survivin 0.041 0.077 -10000 0 -0.15 59 59
EVI5 0.039 0.01 -10000 0 0 33 33
RhoA/GTP 0 0.16 -10000 0 -0.36 66 66
SGOL1 0.036 0.014 -10000 0 0 69 69
CENPA -0.017 0.11 -10000 0 -0.29 61 61
NCAPG 0 0 -10000 0 -10000 0 0
Aurora B/HC8 Proteasome 0.034 0.063 -10000 0 -0.14 56 56
NCAPD2 0 0 -10000 0 -10000 0 0
Aurora B/PP1-gamma 0.036 0.061 -10000 0 -0.14 53 53
RHOA 0.04 0.006 -10000 0 0 13 13
NCAPH 0 0 -10000 0 -10000 0 0
NPM1 -0.027 0.15 -10000 0 -0.36 70 70
RASA1 0.037 0.013 -10000 0 0 56 56
KLHL9 0.039 0.01 -10000 0 0 34 34
mitotic prometaphase -0.001 0.003 -10000 0 -0.011 38 38
proteasomal ubiquitin-dependent protein catabolic process 0.033 0.063 -10000 0 -0.14 56 56
PPP1CC 0.039 0.01 -10000 0 0 32 32
Centraspindlin -0.012 0.17 -10000 0 -0.38 70 70
RhoA/GDP 0.029 0.014 -10000 0 -0.12 4 4
NSUN2 -0.015 0.12 -10000 0 -0.32 68 68
MYLK 0.001 0.056 -10000 0 -0.2 39 39
KIF23 0.035 0.016 -10000 0 0 93 93
VIM -0.012 0.014 0.023 15 -10000 0 15
RACGAP1 0.037 0.014 -10000 0 -0.004 52 52
mitosis 0 0 -10000 0 -10000 0 0
NCL -0.03 0.13 -10000 0 -0.32 86 86
Chromosomal passenger complex -0.035 0.14 -10000 0 -0.35 67 67
Chromosomal passenger complex/EVI5 0.067 0.095 -10000 0 -0.17 55 55
TACC1 0.035 0.015 -10000 0 0 86 86
PPP2R5D 0.039 0.009 -10000 0 0 26 26
CUL3 0.04 0.008 -10000 0 0 19 19
response to DNA damage stimulus 0 0 -10000 0 -10000 0 0
Arf6 signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CENTA1/KIF3B 0.023 0.012 -10000 0 -0.1 1 1
ARNO/beta Arrestin1-2 0.041 0.033 -10000 0 -0.087 10 10
EGFR 0.036 0.014 -10000 0 0 67 67
EPHA2 0.039 0.009 -10000 0 0 26 26
USP6 0.038 0.011 -10000 0 0 42 42
IQSEC1 0.04 0.006 -10000 0 0 13 13
EGFR/EGFR/EGF/EGF 0.041 0.05 -10000 0 -0.13 35 35
ARRB2 0.016 0.017 -10000 0 -0.2 3 3
mol:GTP 0.002 0.017 0.12 5 -0.06 14 19
ARRB1 0.038 0.012 -10000 0 0 48 48
FBXO8 0.037 0.013 -10000 0 0 59 59
TSHR 0.037 0.012 -10000 0 0 54 54
EGF 0.038 0.01 -10000 0 0 38 38
somatostatin receptor activity 0 0 0 9 -0.001 38 47
ARAP2 0 0 0 11 0 35 46
mol:GDP 0.011 0.072 0.15 3 -0.19 31 34
mol:PI-3-4-5-P3 0 0 0 7 0 37 44
ITGA2B 0.04 0.008 -10000 0 0 22 22
ARF6 0.04 0.007 -10000 0 0 16 16
Ephrin A1/EPHA2/NCK1/GIT1 0.06 0.078 -10000 0 -0.12 66 66
ADAP1 0 0 0 9 0 23 32
KIF13B 0.034 0.016 -10000 0 0 95 95
HGF/MET 0.013 0.074 -10000 0 -0.13 102 102
PXN 0.04 0.006 -10000 0 0 10 10
ARF6/GTP 0.013 0.081 0.19 4 -0.21 38 42
EGFR/EGFR/EGF/EGF/ARFGEP100 0.06 0.053 -10000 0 -0.12 33 33
ADRB2 0.04 0.006 -10000 0 0 11 11
receptor agonist activity 0 0 0 8 0 35 43
actin filament binding 0 0 0 6 0 39 45
SRC 0.039 0.009 -10000 0 0 28 28
ITGB3 0.032 0.017 -10000 0 0 116 116
GNAQ 0.038 0.012 -10000 0 0 48 48
EFA6/PI-4-5-P2 0 0 0.001 13 -0.001 26 39
ARF6/GDP 0.008 0.075 0.18 8 -0.22 29 37
ARF6/GDP/GULP/ACAP1 0.025 0.085 -10000 0 -0.22 24 24
alphaIIb/beta3 Integrin/paxillin/GIT1 0.079 0.057 -10000 0 -0.11 35 35
ACAP1 0 0 0 6 -10000 0 6
ACAP2 0 0 0 8 0 36 44
LHCGR/beta Arrestin2 0.03 0.027 -10000 0 -0.062 37 37
EFNA1 0.034 0.016 -10000 0 0 96 96
HGF 0.039 0.009 -10000 0 0 27 27
CYTH3 0 0 0.001 10 -0.001 35 45
CYTH2 0 0.001 0.003 6 -0.004 36 42
NCK1 0.036 0.014 -10000 0 0 70 70
fibronectin binding 0 0 0 8 0 29 37
endosomal lumen acidification 0 0 0 12 0 17 29
microtubule-based process 0 0 -10000 0 -10000 0 0
GULP1 0.032 0.017 -10000 0 0 127 127
GNAQ/ARNO 0.026 0.008 -10000 0 0 48 48
mol:Phosphatidic acid 0 0 0 8 0 36 44
PIP3-E 0.038 0.011 -10000 0 0 45 45
MET 0.027 0.02 -10000 0 0 191 191
GNA14 0.039 0.009 -10000 0 0 29 29
GNA15 0.036 0.014 -10000 0 0 68 68
GIT1 0.039 0.009 -10000 0 0 25 25
mol:PI-4-5-P2 0 0 0.001 13 -0.001 37 50
GNA11 0.037 0.013 -10000 0 0 61 61
LHCGR 0.04 0.008 -10000 0 0 20 20
AGTR1 0.037 0.013 -10000 0 0 57 57
desensitization of G-protein coupled receptor protein signaling pathway 0.03 0.027 -10000 0 -0.062 37 37
IPCEF1/ARNO 0.051 0.046 -10000 0 -0.086 34 34
alphaIIb/beta3 Integrin 0.039 0.05 -10000 0 -0.13 35 35
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
HIF3A 0.037 0.012 -10000 0 0 52 52
oxygen homeostasis 0 0 -10000 0 -10000 0 0
TCEB2 0.039 0.008 -10000 0 0 23 23
TCEB1 0.038 0.011 -10000 0 0 39 39
HIF1A/p53 0.004 0.078 0.22 1 -0.25 33 34
HIF1A 0 0.068 0.16 2 -0.25 24 26
COPS5 0.035 0.014 -10000 0 0 79 79
VHL/Elongin B/Elongin C/RBX1/CUL2 0.083 0.071 -10000 0 -0.12 31 31
FIH (dimer) 0.04 0.008 -10000 0 0 20 20
CDKN2A 0.029 0.019 -10000 0 0 167 167
ARNT/IPAS 0.05 0.028 -10000 0 -0.13 4 4
HIF1AN 0.04 0.008 -10000 0 0 20 20
GNB2L1 0.039 0.009 -10000 0 0 30 30
HIF1A/ARNT 0.015 0.076 0.22 1 -0.25 26 27
CUL2 0.039 0.01 -10000 0 0 34 34
OS9 0.039 0.009 -10000 0 0 26 26
RACK1/Elongin B/Elongin C 0.068 0.039 -10000 0 -0.12 11 11
response to hypoxia 0 0 -10000 0 -10000 0 0
HIF1A/Hsp90 -0.003 0.067 0.15 2 -0.3 16 18
PHD1-3/OS9 0.05 0.079 -10000 0 -0.11 88 88
HIF1A/RACK1/Elongin B/Elongin C 0.049 0.084 -10000 0 -0.25 22 22
VHL 0.039 0.008 -10000 0 0 23 23
HSP90AA1 0 0 -10000 0 -10000 0 0
HIF1A/JAB1 0.015 0.074 0.22 1 -0.25 24 25
EGLN3 0.027 0.019 -10000 0 0 182 182
EGLN2 0.038 0.011 -10000 0 0 41 41
EGLN1 0.039 0.009 -10000 0 0 29 29
TP53 0.026 0.02 -10000 0 0 207 207
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A 0.029 0.11 -10000 0 -0.55 18 18
ARNT 0.037 0.012 -10000 0 0 50 50
ARD1A 0.039 0.009 -10000 0 0 30 30
RBX1 0.036 0.014 -10000 0 0 70 70
HIF1A/p19ARF 0.006 0.08 -10000 0 -0.26 29 29
p75(NTR)-mediated signaling

Figure S67.  Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S67.  Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
Sortilin/TRAF6 0.046 0.05 -10000 0 -0.14 35 35
Necdin/E2F1 0.043 0.039 -10000 0 -0.14 14 14
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E 0.071 0.059 -10000 0 -0.11 40 40
NGF (dimer)/p75(NTR)/BEX1 0.022 0.052 -10000 0 -0.11 61 61
NT-4/5 (dimer)/p75(NTR) 0.029 0.009 -10000 0 -0.12 1 1
IKBKB 0.038 0.011 -10000 0 0 41 41
AKT1 0.026 0.097 0.19 124 -0.18 6 130
IKBKG 0.041 0.002 -10000 0 0 2 2
BDNF 0.04 0.006 -10000 0 0 12 12
MGDIs/NGR/p75(NTR)/LINGO1 0.048 0.021 -10000 0 -0.11 3 3
FURIN 0.039 0.01 -10000 0 0 31 31
proBDNF (dimer)/p75(NTR)/Sortilin 0.068 0.046 -10000 0 -0.12 25 25
LINGO1 0 0 -10000 0 -10000 0 0
Sortilin/TRAF6/NRIF 0.016 0.068 -10000 0 -0.13 72 72
proBDNF (dimer) 0.04 0.006 -10000 0 0 12 12
NTRK1 0.04 0.007 -10000 0 0 16 16
RTN4R 0.037 0.012 -10000 0 0 50 50
neuron apoptosis -0.069 0.15 -10000 0 -0.38 68 68
IRAK1 0.04 0.008 -10000 0 0 19 19
SHC1 0.017 0.009 0.069 7 -0.11 1 8
ARHGDIA 0.037 0.012 -10000 0 0 53 53
RhoA/GTP 0.029 0.014 -10000 0 -0.12 4 4
Gamma Secretase 0.067 0.085 -10000 0 -0.12 63 63
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1 0.055 0.056 -10000 0 -0.1 49 49
MAGEH1 0.038 0.011 -10000 0 0 44 44
proNGF (dimer)/p75(NTR)/Sortilin/Necdin 0.051 0.052 -10000 0 -0.1 37 37
Mammalian IAPs/DIABLO 0.012 0.088 -10000 0 -0.13 129 129
proNGF (dimer) 0 0 -10000 0 -10000 0 0
MAGED1 0.039 0.008 -10000 0 0 24 24
APP 0.038 0.011 -10000 0 0 41 41
NT-4/5 (dimer) 0 0 -10000 0 -10000 0 0
ZNF274 0.038 0.01 -10000 0 0 38 38
RhoA/GDP/RHOGDI 0.048 0.027 0.19 3 -0.11 7 10
NGF 0 0 -10000 0 -10000 0 0
cell cycle arrest -0.014 0.045 0.2 8 -10000 0 8
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK 0.01 0.062 -10000 0 -0.16 50 50
NT-4/5 (dimer)/p75(NTR)/TRAF6 0.05 0.024 -10000 0 -0.11 8 8
NCSTN 0.04 0.008 -10000 0 0 22 22
mol:GTP 0.044 0.034 -10000 0 -0.1 23 23
PSENEN 0.034 0.016 -10000 0 0 96 96
mol:ceramide -0.018 0.036 0.2 10 -10000 0 10
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs 0.009 0.09 -10000 0 -0.32 21 21
p75(NTR)/beta APP 0.048 0.043 -10000 0 -0.13 26 26
BEX1 0.026 0.02 -10000 0 0 200 200
mol:GDP -0.008 0.004 -10000 0 -0.1 1 1
NGF (dimer) -0.004 0.074 -10000 0 -0.1 172 172
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI 0.063 0.035 -10000 0 -0.1 7 7
PIK3R1 0.034 0.016 -10000 0 0 99 99
RAC1/GTP 0.044 0.015 -10000 0 -0.09 1 1
MYD88 0.04 0.006 -10000 0 0 12 12
CHUK 0.038 0.011 -10000 0 0 46 46
NGF (dimer)/p75(NTR)/PKA 0.045 0.035 -10000 0 -0.11 23 23
RHOB 0.04 0.007 -10000 0 0 16 16
RHOA 0.04 0.006 -10000 0 0 13 13
MAGE-G1/E2F1 0.052 0.024 -10000 0 -0.13 2 2
NT3 (dimer) 0.031 0.018 -10000 0 0 133 133
TP53 -0.022 0.047 0.17 14 -0.18 13 27
PRDM4 -0.02 0.036 0.2 9 -10000 0 9
BDNF (dimer) 0.016 0.09 -10000 0 -0.11 168 168
PIK3CA 0.029 0.019 -10000 0 0 166 166
SORT1 0.038 0.011 -10000 0 0 42 42
activation of caspase activity 0.064 0.056 -10000 0 -0.1 40 40
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6 0.062 0.048 -10000 0 -0.11 33 33
RHOC 0.04 0.006 -10000 0 0 10 10
XIAP 0 0 -10000 0 -10000 0 0
MAPK10 -0.012 0.057 0.22 7 -0.2 10 17
DIABLO 0.037 0.013 -10000 0 0 61 61
SMPD2 -0.019 0.036 0.2 10 -10000 0 10
APH1B 0.035 0.014 -10000 0 0 79 79
APH1A 0.038 0.011 -10000 0 0 42 42
proNGF (dimer)/p75(NTR)/Sortilin 0.044 0.037 -10000 0 -0.11 26 26
PSEN1 0.039 0.01 -10000 0 0 31 31
APAF-1/Pro-Caspase 9 0.051 0.039 -10000 0 -0.14 18 18
NT3 (dimer)/p75(NTR) 0.042 0.034 -10000 0 -0.13 8 8
MAPK8 -0.017 0.064 0.24 5 -0.23 13 18
MAPK9 -0.017 0.061 0.24 5 -0.21 12 17
APAF1 0.039 0.009 -10000 0 0 28 28
NTF3 0.031 0.018 -10000 0 0 133 133
NTF4 0 0 -10000 0 -10000 0 0
NDN 0.034 0.016 -10000 0 0 99 99
RAC1/GDP 0.029 0.009 -10000 0 -0.12 1 1
RhoA-B-C/GDP 0.073 0.049 -10000 0 -0.1 27 27
p75 CTF/Sortilin/TRAF6/NRIF 0.069 0.075 -10000 0 -0.13 56 56
RhoA-B-C/GTP 0.044 0.034 -10000 0 -0.1 23 23
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF 0.093 0.066 -10000 0 -0.11 32 32
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6 0.085 0.057 -10000 0 -0.11 32 32
PRKACB 0.038 0.011 -10000 0 0 44 44
proBDNF (dimer)/p75 ECD 0.047 0.046 -10000 0 -0.13 31 31
ChemicalAbstracts:86-01-1 0 0 -10000 0 -10000 0 0
BIRC3 0.025 0.02 -10000 0 0 210 210
BIRC2 0.036 0.014 -10000 0 0 72 72
neuron projection morphogenesis -0.018 0.049 0.12 7 -0.16 22 29
BAD -0.019 0.068 0.23 5 -0.21 18 23
RIPK2 0.032 0.017 -10000 0 0 119 119
NGFR 0.039 0.009 -10000 0 0 25 25
CYCS -0.024 0.04 0.2 8 -0.18 5 13
ADAM17 0.037 0.012 -10000 0 0 52 52
NGF (dimer)/p75(NTR)/TRAF6/RIP2 0.049 0.056 -10000 0 -0.11 44 44
BCL2L11 -0.02 0.068 0.23 5 -0.21 18 23
BDNF (dimer)/p75(NTR) 0.057 0.017 -10000 0 -0.13 1 1
PI3K 0.034 0.058 -10000 0 -0.11 45 45
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1 0.061 0.046 -10000 0 -0.1 27 27
NDNL2 0.038 0.011 -10000 0 0 40 40
YWHAE 0.037 0.013 -10000 0 0 58 58
PRKCI 0.027 0.02 -10000 0 0 192 192
NGF (dimer)/p75(NTR) 0.029 0.009 -10000 0 -0.12 1 1
ChemicalAbstracts:146-91-8 0 0 -10000 0 -10000 0 0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE 0.06 0.051 -10000 0 -0.1 38 38
TRAF6 0.04 0.008 -10000 0 0 19 19
RAC1 0.039 0.009 -10000 0 0 28 28
PRKCZ 0.039 0.009 -10000 0 0 27 27
PLG 0.038 0.011 -10000 0 0 41 41
oligodendrocyte cell fate commitment 0 0 -10000 0 -10000 0 0
CASP6 0.014 0.044 0.16 8 -0.17 23 31
SQSTM1 0.038 0.011 -10000 0 0 46 46
NGFRAP1 0.04 0.007 -10000 0 0 15 15
CASP3 -0.021 0.071 0.24 4 -0.22 25 29
E2F1 0.038 0.011 -10000 0 0 39 39
CASP9 0.039 0.008 -10000 0 0 24 24
IKK complex 0.045 0.1 -10000 0 -0.25 27 27
NGF (dimer)/TRKA 0.03 0.005 -10000 0 -10000 0 0
MMP7 0.016 0.02 -10000 0 0 333 333
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF 0.074 0.055 -10000 0 -0.1 33 33
MMP3 0.037 0.012 -10000 0 0 53 53
APAF-1/Caspase 9 -0.056 0.059 -10000 0 -0.19 51 51
S1P3 pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PDGFRB 0.036 0.013 -10000 0 0 65 65
mol:S1P 0.001 0.007 -10000 0 -0.028 23 23
S1P1/S1P/Gi 0.007 0.079 -10000 0 -0.18 62 62
GNAO1 0.034 0.023 -10000 0 -0.009 105 105
S1P/S1P3/G12/G13 0.047 0.03 -10000 0 -0.064 23 23
AKT1 0.015 0.099 -10000 0 -0.45 19 19
AKT3 -0.019 0.23 -10000 0 -0.91 29 29
mol:GTP 0 0 -10000 0 -10000 0 0
PDGFB-D/PDGFRB 0.036 0.013 -10000 0 0 65 65
GNAI2 0.039 0.019 -10000 0 -0.03 35 35
GNAI3 0.037 0.019 -10000 0 -0.013 62 62
GNAI1 0.034 0.022 -10000 0 -0.007 110 110
mol:GDP 0 0 -10000 0 -10000 0 0
S1PR3 0.001 0.007 0.011 3 -0.029 23 26
S1PR2 0 0 -10000 0 -10000 0 0
EDG1 0.04 0.006 -10000 0 0 11 11
mol:Ca2+ 0 0.1 0.16 3 -0.27 46 49
MAPK3 -0.009 0.094 0.14 4 -0.25 51 55
MAPK1 -0.005 0.09 0.14 4 -0.26 41 45
JAK2 -0.015 0.11 0.2 3 -0.29 54 57
CXCR4 -0.01 0.099 0.14 7 -0.27 49 56
FLT1 0.04 0.022 -10000 0 -0.024 48 48
RhoA/GDP 0.029 0.014 -10000 0 -0.12 4 4
Rac1/GDP 0.029 0.009 -10000 0 -0.12 1 1
SRC -0.009 0.093 0.14 3 -0.26 46 49
S1P/S1P3/Gi 0 0.1 0.16 3 -0.28 45 48
RAC1 0.039 0.009 -10000 0 0 28 28
RhoA/GTP 0.012 0.1 -10000 0 -0.24 51 51
VEGFA 0.003 0.01 0.017 98 -0.038 22 120
S1P/S1P2/Gi -0.003 0.088 0.14 3 -0.19 77 80
VEGFR1 homodimer/VEGFA homodimer 0.036 0.032 -10000 0 -0.087 25 25
RHOA 0.04 0.006 -10000 0 0 13 13
S1P/S1P3/Gq 0.017 0.04 -10000 0 -0.15 26 26
GNAQ 0.038 0.012 -10000 0 0 48 48
GNAZ 0.037 0.02 -10000 0 -0.013 64 64
G12/G13 0.053 0.028 -10000 0 -0.13 8 8
GNA14 0.039 0.009 -10000 0 0 29 29
GNA15 0.036 0.014 -10000 0 0 68 68
GNA12 0.039 0.01 -10000 0 0 33 33
GNA13 0.039 0.008 -10000 0 0 23 23
GNA11 0.037 0.013 -10000 0 0 61 61
Rac1/GTP 0.01 0.1 -10000 0 -0.25 49 49
PLK1 signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
regulation of centriole-centriole cohesion 0.008 0.053 0.18 46 -0.088 3 49
BUB1B -0.024 0.081 -10000 0 -0.21 67 67
PLK1 -0.003 0.036 0.08 2 -0.099 42 44
PLK1S1 -0.002 0.02 0.046 3 -0.054 41 44
KIF2A -0.003 0.032 0.071 2 -0.089 42 44
regulation of mitotic centrosome separation -0.003 0.036 0.08 2 -0.099 42 44
GOLGA2 0.04 0.008 -10000 0 0 22 22
Hec1/SPC24 -0.01 0.025 -10000 0 -0.08 47 47
WEE1 -0.01 0.083 -10000 0 -0.34 22 22
cytokinesis -0.037 0.13 0.15 2 -0.3 89 91
PP2A-alpha B56 0 0.24 -10000 0 -0.7 57 57
AURKA -0.002 0.022 0.051 4 -0.063 34 38
PICH/PLK1 -0.034 0.068 -10000 0 -0.16 106 106
CENPE -0.008 0.035 0.15 2 -0.13 20 22
RhoA/GTP 0.029 0.014 -10000 0 -0.12 4 4
positive regulation of microtubule depolymerization -0.003 0.032 0.071 2 -0.089 42 44
PPP2CA 0.04 0.008 -10000 0 0 22 22
FZR1 0.037 0.012 -10000 0 0 54 54
TPX2 -0.026 0.096 -10000 0 -0.25 84 84
PAK1 0.037 0.014 -10000 0 0 65 65
SPC24 0 0 -10000 0 -10000 0 0
FBXW11 0.04 0.008 -10000 0 0 22 22
CLSPN 0.008 0.034 -10000 0 -0.28 5 5
GORASP1 0.041 0.005 -10000 0 0 8 8
metaphase 0 0.004 0.015 9 -0.013 27 36
mol:GTP 0 0 -10000 0 -10000 0 0
NLP -0.002 0.02 0.046 3 -0.054 41 44
G2 phase of mitotic cell cycle -0.001 0.003 0.012 9 -10000 0 9
STAG2 0.039 0.01 -10000 0 0 34 34
GRASP65/GM130/RAB1/GTP 0.017 0.065 -10000 0 -0.64 4 4
spindle elongation -0.003 0.036 0.08 2 -0.099 42 44
ODF2 0.04 0.009 -10000 0 0 24 24
BUB1 -0.041 0.24 -10000 0 -0.74 57 57
TPT1 -0.002 0.049 -10000 0 -0.19 29 29
CDC25C -0.007 0.088 -10000 0 -0.34 33 33
CDC25B 0.024 0.03 -10000 0 -0.03 114 114
SGOL1 -0.008 0.053 0.088 3 -0.18 46 49
RHOA 0.04 0.006 -10000 0 0 13 13
CCNB1/CDK1 0.005 0.12 -10000 0 -0.21 117 117
CDC14B -0.01 0.006 0.011 31 -10000 0 31
CDC20 0.034 0.016 -10000 0 0 96 96
PLK1/PBIP1 -0.004 0.032 -10000 0 -0.1 34 34
mitosis -0.001 0.003 0.012 6 -0.012 4 10
FBXO5 -0.016 0.063 0.11 2 -0.18 54 56
CDC2 0.027 0.023 -10000 0 -0.028 30 30
NDC80 0 0 -10000 0 -10000 0 0
metaphase plate congression 0.002 0.052 -10000 0 -0.25 19 19
ERCC6L -0.029 0.098 -10000 0 -0.2 113 113
NLP/gamma Tubulin -0.003 0.031 0.062 2 -0.088 46 48
microtubule cytoskeleton organization -0.002 0.049 -10000 0 -0.19 29 29
G2/M transition DNA damage checkpoint 0 0.002 0.011 9 -10000 0 9
PPP1R12A 0.04 0.009 -10000 0 0 24 24
interphase 0 0.002 0.011 9 -10000 0 9
PLK1/PRC1-2 0.013 0.083 -10000 0 -0.15 87 87
GRASP65/GM130/RAB1/GTP/PLK1 0.051 0.058 -10000 0 -0.1 42 42
RAB1A 0.039 0.009 -10000 0 0 26 26
prophase 0 0 -10000 0 -10000 0 0
Aurora A/BORA -0.002 0.025 0.063 5 -0.068 38 43
mitotic prometaphase -0.001 0.004 0.018 19 -10000 0 19
proteasomal ubiquitin-dependent protein catabolic process -0.005 0.078 -10000 0 -0.27 27 27
microtubule-based process 0.014 0.051 0.096 1 -0.14 35 36
Golgi organization -0.003 0.036 0.08 2 -0.099 42 44
Cohesin/SA2 0.013 0.046 0.091 1 -0.096 59 60
PPP1CB/MYPT1 0.051 0.04 -10000 0 -0.14 22 22
KIF20A 0.032 0.017 -10000 0 0 125 125
APC/C/CDC20 0.016 0.05 -10000 0 -0.14 36 36
PPP2R1A 0.039 0.009 -10000 0 0 28 28
chromosome segregation -0.004 0.031 -10000 0 -0.099 34 34
PRC1 0.035 0.015 -10000 0 0 80 80
ECT2 0.034 0.11 0.22 129 -0.15 48 177
C13orf34 -0.002 0.029 0.066 4 -0.078 39 43
NUDC 0.001 0.052 -10000 0 -0.25 19 19
regulation of attachment of spindle microtubules to kinetochore -0.024 0.08 -10000 0 -0.2 67 67
spindle assembly -0.003 0.032 0.072 2 -0.091 40 42
spindle stabilization -0.002 0.02 0.046 3 -0.054 41 44
APC/C/HCDH1 0.031 0.012 -10000 0 -10000 0 0
MKLP2/PLK1 0.014 0.051 0.096 1 -0.14 35 36
CCNB1 0.026 0.027 -10000 0 -0.029 64 64
PPP1CB 0.04 0.008 -10000 0 0 22 22
BTRC 0.04 0.007 -10000 0 0 17 17
ROCK2 -0.007 0.093 -10000 0 -0.33 38 38
TUBG1 -0.003 0.053 -10000 0 -0.21 29 29
G2/M transition of mitotic cell cycle -0.037 0.097 -10000 0 -0.21 112 112
MLF1IP -0.008 0.007 0.012 12 -10000 0 12
INCENP 0.04 0.005 -10000 0 0 6 6
Reelin signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CDK5R1/CDK5 0.045 0.04 -10000 0 -0.13 19 19
VLDLR 0.032 0.017 -10000 0 0 121 121
CRKL 0.038 0.01 -10000 0 0 36 36
LRPAP1 0.036 0.014 -10000 0 0 72 72
FYN 0.034 0.016 -10000 0 0 94 94
ITGA3 0.034 0.016 -10000 0 0 98 98
RELN/VLDLR/Fyn 0.033 0.067 -10000 0 -0.13 53 53
MAPK8IP1/MKK7/MAP3K11/JNK1 0.091 0.062 -10000 0 -0.11 18 18
AKT1 0.003 0.072 -10000 0 -0.17 54 54
MAP2K7 0.038 0.011 -10000 0 0 41 41
RAPGEF1 0.039 0.009 -10000 0 0 26 26
DAB1 0.04 0.008 -10000 0 0 21 21
RELN/LRP8/DAB1 0.059 0.038 -10000 0 -0.1 6 6
LRPAP1/LRP8 0.041 0.051 -10000 0 -0.14 35 35
RELN/LRP8/DAB1/Fyn 0.065 0.055 -10000 0 -0.1 33 33
DAB1/alpha3/beta1 Integrin 0.029 0.082 -10000 0 -0.18 12 12
long-term memory 0.069 0.069 -10000 0 -0.11 32 32
DAB1/LIS1 0.058 0.081 -10000 0 -0.11 56 56
DAB1/CRLK/C3G 0.046 0.072 -10000 0 -0.18 2 2
PIK3CA 0.029 0.019 -10000 0 0 166 166
DAB1/NCK2 0.064 0.081 -10000 0 -0.18 2 2
ARHGEF2 0.038 0.011 -10000 0 0 39 39
mol:Src family inhibitors PP1 and PP2 0 0 -10000 0 -10000 0 0
GRIN2A 0.033 0.017 -10000 0 0 111 111
CDK5R1 0.038 0.011 -10000 0 0 40 40
RELN 0.034 0.016 -10000 0 0 96 96
PIK3R1 0.034 0.016 -10000 0 0 99 99
RELN/LRP8/Fyn 0.046 0.056 -10000 0 -0.12 34 34
GRIN2A/RELN/LRP8/DAB1/Fyn 0.073 0.069 -10000 0 -0.11 35 35
MAPK8 0.039 0.009 -10000 0 0 29 29
RELN/VLDLR/DAB1 0.043 0.054 -10000 0 -0.1 38 38
ITGB1 0.038 0.01 -10000 0 0 36 36
MAP1B -0.002 0.062 0.21 21 -0.2 4 25
RELN/LRP8 0.05 0.054 -10000 0 -0.12 29 29
GRIN2B/RELN/LRP8/DAB1/Fyn 0.077 0.067 -10000 0 -0.11 29 29
PI3K 0.023 0.06 -10000 0 -0.15 44 44
mol:PP2 0 0 -10000 0 -10000 0 0
alpha3/beta1 Integrin 0.03 0.065 -10000 0 -0.14 68 68
RAP1A -0.008 0.088 0.28 21 -10000 0 21
PAFAH1B1 0.038 0.012 -10000 0 0 49 49
MAPK8IP1 0.039 0.009 -10000 0 0 30 30
CRLK/C3G 0.055 0.019 -10000 0 -10000 0 0
GRIN2B 0.037 0.013 -10000 0 0 59 59
NCK2 0.041 0.004 -10000 0 0 6 6
neuron differentiation 0.022 0.059 0.17 2 -0.22 9 11
neuron adhesion -0.016 0.097 0.27 26 -0.25 1 27
LRP8 0.039 0.01 -10000 0 0 35 35
GSK3B -0.002 0.074 0.18 7 -0.26 13 20
RELN/VLDLR/DAB1/Fyn 0.05 0.067 -10000 0 -0.11 52 52
MAP3K11 0.04 0.007 -10000 0 0 14 14
RELN/VLDLR/DAB1/P13K -0.003 0.066 -10000 0 -0.16 57 57
CDK5 0.036 0.014 -10000 0 0 69 69
MAPT -0.004 0.074 0.74 5 -10000 0 5
neuron migration -0.001 0.088 0.26 15 -0.24 13 28
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1 0.022 0.058 0.17 2 -0.2 10 12
RELN/VLDLR 0.053 0.072 -10000 0 -0.11 60 60
RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1 -0.031 0.2 0.33 23 -0.98 21 44
VDR 0.038 0.011 -10000 0 0 43 43
FAM120B 0 0 -10000 0 -10000 0 0
RXRs/LXRs/DNA/9cRA 0.022 0.092 -10000 0 -0.23 53 53
RXRs/LXRs/DNA/Oxysterols 0.012 0.13 -10000 0 -0.34 55 55
MED1 0 0 -10000 0 -10000 0 0
mol:9cRA 0.001 0.015 0.037 2 -0.045 48 50
RARs/THRs/DNA/Src-1 -0.004 0.093 -10000 0 -0.26 34 34
RXRs/NUR77 0.074 0.071 -10000 0 -0.11 38 38
RXRs/PPAR 0.014 0.059 -10000 0 -0.17 20 20
NCOR2 0.039 0.01 -10000 0 0 31 31
VDR/VDR/Vit D3 0.023 0.031 -10000 0 -0.12 22 22
RARs/VDR/DNA/Vit D3 0.065 0.068 -10000 0 -0.11 59 59
RARA 0.039 0.01 -10000 0 0 31 31
NCOA1 0.04 0.008 -10000 0 0 22 22
VDR/VDR/DNA 0.038 0.011 -10000 0 0 43 43
RARs/RARs/DNA/9cRA 0.05 0.053 -10000 0 -0.1 46 46
RARG 0.039 0.009 -10000 0 0 26 26
RPS6KB1 -0.012 0.11 0.56 9 -0.4 21 30
RARs/THRs/DNA/SMRT -0.002 0.088 -10000 0 -0.17 102 102
THRA 0.039 0.01 -10000 0 0 34 34
mol:Bile acids 0 0 -10000 0 -10000 0 0
VDR/Vit D3/DNA 0.023 0.031 -10000 0 -0.12 22 22
RXRs/PPAR/9cRA/PGJ2/DNA 0.063 0.077 0.29 10 -0.15 33 43
NR1H4 0.04 0.006 -10000 0 0 11 11
RXRs/LXRs/DNA 0.092 0.1 -10000 0 -0.19 37 37
NR1H2 0.034 0.031 -10000 0 -0.058 50 50
NR1H3 0.035 0.034 -10000 0 -0.063 53 53
RXRs/VDR/DNA/Vit D3 0.071 0.07 -10000 0 -0.1 47 47
NR4A1 0.034 0.016 -10000 0 0 98 98
mol:ATRA 0 0 -10000 0 -10000 0 0
RXRs/FXR/9cRA/MED1 0.02 0.043 -10000 0 -0.14 10 10
RXRG 0.031 0.03 -10000 0 -0.055 43 43
RXR alpha/CCPG 0.025 0.022 -10000 0 -0.038 40 40
RXRA 0.034 0.031 -10000 0 -0.056 47 47
RXRB 0.036 0.033 -10000 0 -0.06 56 56
THRB 0.033 0.016 -10000 0 0 107 107
PPARG 0.039 0.01 -10000 0 0 32 32
PPARD 0.04 0.006 -10000 0 0 13 13
TNF 0.004 0.13 -10000 0 -0.52 8 8
mol:Oxysterols 0 0.014 -10000 0 -0.04 57 57
cholesterol transport 0.013 0.13 -10000 0 -0.34 55 55
PPARA 0.032 0.017 -10000 0 0 126 126
mol:Vit D3 0 0 -10000 0 -10000 0 0
RARB 0.036 0.014 -10000 0 0 75 75
RXRs/NUR77/BCL2 0.019 0.045 -10000 0 -0.13 24 24
SREBF1 0.004 0.12 -10000 0 -0.35 44 44
RXRs/RXRs/DNA/9cRA 0.063 0.077 0.29 10 -0.15 33 43
ABCA1 -0.045 0.26 -10000 0 -0.82 53 53
RARs/THRs 0.068 0.091 -10000 0 -0.12 81 81
RXRs/FXR 0.085 0.067 -10000 0 -0.11 32 32
BCL2 0.036 0.014 -10000 0 0 67 67
Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3 0.05 0.021 -10000 0 -0.11 5 5
response to insulin stimulus 0 0 -10000 0 -10000 0 0
RIPK1 0.039 0.01 -10000 0 0 32 32
response to stress 0 0 -10000 0 -10000 0 0
MAP2K6 0.034 0.016 -10000 0 0 94 94
mol:GTP 0 0 -10000 0 -10000 0 0
MAP2K4 0.036 0.013 -10000 0 0 65 65
RAC1-CDC42/GTP/PAK family 0.007 0.04 -10000 0 -0.14 27 27
response to UV 0 0 -10000 0 -10000 0 0
YES1 0.037 0.012 -10000 0 0 51 51
interleukin-1 receptor activity 0 0 -10000 0 -10000 0 0
tumor necrosis factor receptor activity 0 0 -10000 0 -10000 0 0
MAP3K3 0.04 0.007 -10000 0 0 14 14
FYN 0.034 0.016 -10000 0 0 94 94
MAP3K12 0.04 0.006 -10000 0 0 13 13
FGR 0.04 0.007 -10000 0 0 15 15
p38 alpha/TAB1 -0.002 0.12 0.21 1 -0.26 60 61
PRKG1 0.039 0.009 -10000 0 0 30 30
DUSP8 0.039 0.009 -10000 0 0 30 30
PGK/cGMP/p38 alpha -0.007 0.12 0.19 1 -0.26 61 62
apoptosis -0.003 0.12 0.2 1 -0.25 60 61
RAL/GTP 0.046 0.036 -10000 0 -0.11 24 24
LYN 0.035 0.015 -10000 0 0 83 83
DUSP1 0.026 0.02 -10000 0 0 196 196
PAK1 0.036 0.013 -10000 0 0 65 65
SRC 0.039 0.009 -10000 0 0 28 28
RAC1/OSM/MEKK3/MKK3 0.091 0.038 -10000 0 -0.11 1 1
TRAF6 0.04 0.008 -10000 0 0 19 19
RAC1 0.039 0.009 -10000 0 0 28 28
epidermal growth factor receptor activity 0 0 -10000 0 -10000 0 0
mol:LPS 0 0 -10000 0 -10000 0 0
mol:cGMP 0 0 -10000 0 -10000 0 0
CCM2 0.041 0.005 -10000 0 0 9 9
RAC1-CDC42/GTP 0.05 0.02 -10000 0 -0.14 3 3
MAPK11 -0.032 0.13 0.21 1 -0.28 72 73
BLK 0.033 0.017 -10000 0 0 114 114
HCK 0.036 0.013 -10000 0 0 65 65
MAP2K3 0.038 0.011 -10000 0 0 43 43
DUSP16 0.036 0.014 -10000 0 0 75 75
DUSP10 0.034 0.016 -10000 0 0 102 102
TRAF6/MEKK3 0.048 0.021 -10000 0 -0.097 8 8
MAP3K7IP1 0.037 0.012 -10000 0 0 51 51
MAPK14 -0.015 0.12 0.2 2 -0.28 63 65
positive regulation of innate immune response -0.028 0.14 0.23 2 -0.33 65 67
LCK 0.039 0.009 -10000 0 0 25 25
p38alpha-beta/MKP7 -0.019 0.14 -10000 0 -0.32 63 63
p38alpha-beta/MKP5 -0.023 0.15 -10000 0 -0.31 72 72
PGK/cGMP 0.029 0.007 -10000 0 -10000 0 0
PAK2 0.033 0.017 -10000 0 0 111 111
p38alpha-beta/MKP1 -0.029 0.14 0.26 1 -0.33 66 67
CDC42 0.04 0.007 -10000 0 0 18 18
RALB 0.039 0.009 -10000 0 0 25 25
RALA 0.04 0.008 -10000 0 0 19 19
PAK3 0.037 0.013 -10000 0 0 60 60
Regulation of Telomerase

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
Telomerase catalytic core complex -0.031 0.18 -10000 0 -0.5 23 23
RAD9A 0.041 0.004 -10000 0 0 5 5
AP1 0.002 0.083 -10000 0 -0.15 113 113
IFNAR2 0.029 0.028 -10000 0 -0.033 74 74
AKT1 0.012 0.037 -10000 0 -0.15 5 5
ER alpha/Oestrogen 0.012 0.043 -10000 0 -0.12 42 42
NFX1/SIN3/HDAC complex 0.002 0.079 -10000 0 -0.27 26 26
EGF 0.038 0.011 -10000 0 0 38 38
SMG5 0 0 -10000 0 -10000 0 0
SMG6 0 0 -10000 0 -10000 0 0
SP3/HDAC2 0.044 0.043 -10000 0 -0.13 6 6
TERT/c-Abl -0.021 0.18 -10000 0 -0.47 25 25
SAP18 0.039 0.009 -10000 0 0 24 24
MRN complex 0.048 0.071 -10000 0 -0.15 50 50
WT1 0.029 0.027 -10000 0 -0.033 71 71
WRN 0.033 0.016 -10000 0 0 108 108
SP1 0.031 0.03 -10000 0 -0.041 77 77
SP3 0.04 0.008 -10000 0 -0.005 12 12
TERF2IP 0.037 0.013 -10000 0 0 61 61
Telomerase/Nucleolin -0.019 0.18 -10000 0 -0.44 31 31
Mad/Max 0.054 0.025 -10000 0 -10000 0 0
TERT -0.035 0.18 -10000 0 -0.51 22 22
CCND1 -0.11 0.37 -10000 0 -0.96 81 81
MAX 0.04 0.008 -10000 0 -0.005 14 14
RBBP7 0.039 0.009 -10000 0 0 25 25
RBBP4 0.038 0.011 -10000 0 0 40 40
TERF2 0.036 0.02 0.094 43 0 55 98
PTGES3 0.037 0.012 -10000 0 0 55 55
SIN3A 0.039 0.009 -10000 0 0 30 30
Telomerase/911 0.022 0.078 -10000 0 -0.28 20 20
CDKN1B 0 0.083 0.19 8 -0.32 21 29
RAD1 0.037 0.012 -10000 0 0 51 51
XRCC5 0.038 0.011 -10000 0 0 41 41
XRCC6 0.036 0.014 -10000 0 0 69 69
SAP30 0.038 0.011 -10000 0 0 46 46
TRF2/PARP2 0.049 0.035 -10000 0 -0.13 10 10
UBE3A 0.038 0.011 -10000 0 0 35 35
JUN 0.035 0.015 -10000 0 -0.03 2 2
E6 -0.001 0.004 -10000 0 -10000 0 0
HPV-16 E6/E6AP 0.022 0.022 -10000 0 -0.12 2 2
FOS 0.025 0.02 -10000 0 -0.001 205 205
IFN-gamma/IRF1 0.024 0.081 -10000 0 -0.15 81 81
PARP2 0.038 0.011 -10000 0 0 40 40
BLM 0.036 0.013 -10000 0 0 66 66
Telomerase 0.003 0.062 -10000 0 -0.26 19 19
IRF1 0.029 0.04 -10000 0 -0.14 20 20
ESR1 0.034 0.015 -10000 0 0 91 91
KU/TER 0.04 0.056 -10000 0 -0.16 33 33
ATM/TRF2 0.038 0.056 -10000 0 -0.14 41 41
ubiquitin-dependent protein catabolic process 0.003 0.084 0.18 4 -0.26 27 31
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex 0.002 0.085 0.18 4 -0.26 27 31
HDAC1 0.037 0.012 -10000 0 0 49 49
HDAC2 0.03 0.03 -10000 0 -0.04 74 74
ATM 0.005 0.065 -10000 0 -0.24 33 33
SMAD3 -0.012 0.016 0.025 70 -10000 0 70
ABL1 0.039 0.01 -10000 0 0 32 32
MXD1 0.04 0.008 -10000 0 -0.002 16 16
MRE11A 0.038 0.012 -10000 0 0 49 49
HUS1 0.04 0.006 -10000 0 0 10 10
RPS6KB1 0.038 0.01 -10000 0 0 37 37
TERT/NF kappa B1/14-3-3 -0.007 0.18 -10000 0 -0.49 18 18
NR2F2 0.039 0.012 -10000 0 0 34 34
MAPK3 -0.016 0.014 0.021 50 -0.039 8 58
MAPK1 -0.016 0.014 0.021 45 -0.039 6 51
TGFB1/TGF beta receptor Type II 0.036 0.014 -10000 0 0 69 69
NFKB1 0.036 0.013 -10000 0 0 66 66
HNRNPC 0 0 -10000 0 -10000 0 0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis 0.005 0.065 -10000 0 -0.24 33 33
NBN 0.035 0.015 -10000 0 0 87 87
EGFR 0.036 0.014 -10000 0 0 67 67
mol:Oestrogen 0 0.002 -10000 0 -10000 0 0
EGF/EGFR 0.041 0.051 -10000 0 -0.14 35 35
MYC 0.023 0.021 -10000 0 0 245 245
IL2 0.03 0.031 -10000 0 -0.042 77 77
KU 0.04 0.056 -10000 0 -0.16 33 33
RAD50 0.039 0.01 -10000 0 0 35 35
HSP90AA1 0 0 -10000 0 -10000 0 0
TGFB1 0.036 0.014 -10000 0 0 69 69
TRF2/BLM 0.045 0.042 -10000 0 -0.13 20 20
FRAP1 0.039 0.009 -10000 0 0 28 28
KU/TERT -0.015 0.19 -10000 0 -0.48 25 25
SP1/HDAC2 0.043 0.05 -10000 0 -0.11 16 16
PINX1 0.032 0.017 -10000 0 0 117 117
Telomerase/EST1A -0.025 0.16 -10000 0 -0.43 30 30
Smad3/Myc 0.016 0.038 -10000 0 -0.14 18 18
911 complex 0.072 0.034 -10000 0 -0.12 8 8
IFNG 0.034 0.035 0.11 2 -0.11 24 26
Telomerase/PinX1 -0.026 0.17 -10000 0 -0.43 30 30
Telomerase/AKT1/mTOR/p70S6K 0.001 0.096 -10000 0 -0.26 36 36
SIN3B 0.036 0.014 -10000 0 0 67 67
YWHAE 0.037 0.013 -10000 0 0 58 58
Telomerase/EST1B -0.025 0.16 -10000 0 -0.43 30 30
response to DNA damage stimulus 0 0.035 0.1 3 -0.1 49 52
MRN complex/TRF2/Rap1 0.067 0.08 -10000 0 -0.14 37 37
TRF2/WRN 0.04 0.041 -10000 0 -0.11 23 23
Telomerase/hnRNP C1/C2 -0.025 0.16 -10000 0 -0.43 30 30
E2F1 0.03 0.027 -10000 0 -0.033 73 73
ZNFX1 0 0.001 -10000 0 -10000 0 0
PIF1 0 0 -10000 0 -10000 0 0
NCL 0.039 0.009 -10000 0 0 29 29
DKC1 0.04 0.008 -10000 0 0 20 20
telomeric DNA binding 0 0 -10000 0 -10000 0 0
ErbB2/ErbB3 signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
USP8 -0.012 0.011 0.016 40 -10000 0 40
RAS family/GTP 0.023 0.1 0.23 1 -0.21 28 29
NFATC4 -0.011 0.09 0.27 26 -0.18 4 30
ERBB2IP 0.036 0.015 -10000 0 -0.003 64 64
HSP90 (dimer) 0 0 -10000 0 -10000 0 0
mammary gland morphogenesis 0.001 0.08 0.2 15 -0.15 51 66
JUN 0.012 0.088 0.22 12 -10000 0 12
HRAS 0.039 0.01 -10000 0 0 31 31
DOCK7 -0.02 0.084 0.21 22 -0.21 10 32
ErbB2/ErbB3/neuregulin 1 beta/SHC 0.041 0.078 0.21 25 -0.12 62 87
AKT1 -0.005 0.012 0.021 39 -10000 0 39
BAD -0.014 0.007 0.011 20 -10000 0 20
MAPK10 -0.003 0.078 0.21 35 -0.15 2 37
mol:GTP 0 0.002 -10000 0 -10000 0 0
ErbB2/ErbB3/neuregulin 1 beta 0.003 0.086 0.21 15 -0.16 49 64
RAF1 0.011 0.11 0.25 22 -0.23 27 49
ErbB2/ErbB3/neuregulin 2 0.028 0.071 0.19 30 -0.12 70 100
STAT3 -0.023 0.25 -10000 0 -0.91 38 38
cell migration -0.003 0.081 0.22 33 -0.18 10 43
mol:PI-3-4-5-P3 -0.001 0.002 0.016 1 -10000 0 1
cell proliferation -0.023 0.23 0.41 3 -0.54 54 57
FOS -0.029 0.22 0.33 10 -0.4 124 134
NRAS 0.039 0.009 -10000 0 0 30 30
mol:Ca2+ 0.001 0.08 0.2 15 -0.15 51 66
MAPK3 -0.006 0.19 0.36 5 -0.47 41 46
MAPK1 -0.016 0.19 0.36 4 -0.47 47 51
JAK2 -0.019 0.081 0.24 14 -0.23 6 20
NF2 0.005 0.076 -10000 0 -0.69 6 6
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1 0 0.073 0.18 4 -0.17 62 66
NRG1 0.036 0.014 -10000 0 0 74 74
GRB2/SOS1 0.047 0.044 -10000 0 -0.14 24 24
MAPK8 -0.017 0.11 0.24 5 -0.22 71 76
MAPK9 -0.007 0.077 0.21 32 -0.16 4 36
ERBB2 -0.024 0.04 0.26 9 -10000 0 9
ERBB3 0.031 0.018 -10000 0 0 134 134
SHC1 0.04 0.008 -10000 0 0 23 23
RAC1 0.039 0.009 -10000 0 0 28 28
apoptosis 0.005 0.025 0.18 1 -0.21 6 7
STAT3 (dimer) -0.019 0.24 -10000 0 -0.89 38 38
RNF41 -0.016 0.015 0.048 10 -10000 0 10
FRAP1 -0.014 0.008 0.011 20 -10000 0 20
RAC1-CDC42/GTP -0.029 0.056 0.088 29 -0.14 44 73
ErbB2/ErbB2/HSP90 (dimer) -0.023 0.015 0.019 7 -0.12 5 12
CHRNA1 0.01 0.15 0.35 4 -0.35 33 37
myelination -0.004 0.11 0.29 38 -0.21 2 40
PPP3CB -0.016 0.082 0.2 25 -0.2 4 29
KRAS 0.034 0.016 -10000 0 0 95 95
RAC1-CDC42/GDP 0.027 0.097 0.21 1 -0.17 64 65
NRG2 0.041 0.005 -10000 0 0 8 8
mol:GDP 0 0.072 0.18 4 -0.17 62 66
SOS1 0.037 0.012 -10000 0 0 51 51
MAP2K2 -0.002 0.1 0.21 35 -0.22 43 78
SRC 0.039 0.009 -10000 0 0 28 28
mol:cAMP -0.001 0.001 -10000 0 -10000 0 0
PTPN11 -0.019 0.086 0.24 15 -0.2 10 25
MAP2K1 -0.01 0.19 0.38 1 -0.5 32 33
heart morphogenesis 0.001 0.08 0.2 15 -0.15 51 66
RAS family/GDP 0.032 0.1 0.23 1 -0.18 48 49
GRB2 0.04 0.008 -10000 0 0 21 21
PRKACA 0.008 0.079 -10000 0 -0.72 6 6
CHRNE 0.009 0.024 0.084 8 -10000 0 8
HSP90AA1 0 0 -10000 0 -10000 0 0
activation of caspase activity 0.005 0.012 -10000 0 -0.021 39 39
nervous system development 0.001 0.08 0.2 15 -0.15 51 66
CDC42 0.04 0.007 -10000 0 0 18 18
Canonical NF-kappaB pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
FBXW11 0.036 0.027 0.081 2 -0.069 29 31
mol:GTP 0 0 -10000 0 -10000 0 0
NF kappa B1 p50/RelA/I kappa B alpha -0.003 0.12 0.26 3 -0.27 57 60
ERC1 0 0 -10000 0 -10000 0 0
RIP2/NOD2 0.014 0.041 -10000 0 -0.12 41 41
NFKBIA -0.036 0.063 0.21 3 -0.27 29 32
BIRC2 0.036 0.014 -10000 0 0 72 72
IKBKB 0.038 0.011 -10000 0 0 41 41
RIPK2 0.032 0.017 -10000 0 0 119 119
IKBKG -0.003 0.11 -10000 0 -0.29 49 49
IKK complex/A20 0.035 0.12 -10000 0 -0.31 30 30
NEMO/A20/RIP2 0.032 0.017 -10000 0 0 119 119
XPO1 0.039 0.01 -10000 0 0 35 35
NEMO/ATM 0.006 0.12 -10000 0 -0.35 36 36
tumor necrosis factor receptor activity 0 0 -10000 0 -10000 0 0
RAN 0.04 0.008 -10000 0 0 21 21
Exportin 1/RanGTP 0.045 0.035 -10000 0 -0.11 24 24
IKK complex/ELKS 0.008 0.11 -10000 0 -0.28 47 47
BCL10/MALT1/TRAF6 0.065 0.047 -10000 0 -0.12 20 20
NOD2 0 0 -10000 0 -10000 0 0
NFKB1 0.033 0.027 -10000 0 -0.071 25 25
RELA 0.036 0.028 0.08 3 -0.068 33 36
MALT1 0.036 0.014 -10000 0 0 70 70
cIAP1/UbcH5C 0.04 0.053 -10000 0 -0.14 39 39
ATM 0.036 0.014 -10000 0 0 69 69
TNF/TNFR1A 0.047 0.038 -10000 0 -0.13 16 16
TRAF6 0.04 0.008 -10000 0 0 19 19
PRKCA 0.035 0.015 -10000 0 0 86 86
CHUK 0.038 0.011 -10000 0 0 46 46
UBE2D3 0.039 0.009 -10000 0 0 30 30
TNF 0.04 0.008 -10000 0 0 22 22
NF kappa B1 p50/RelA 0.058 0.08 -10000 0 -0.15 60 60
BCL10 0.041 0.005 -10000 0 0 8 8
proteasomal ubiquitin-dependent protein catabolic process -0.035 0.063 0.21 3 -0.27 29 32
beta TrCP1/SCF ubiquitin ligase complex 0.036 0.027 0.081 2 -0.069 29 31
TNFRSF1A 0.036 0.014 -10000 0 0 72 72
IKK complex 0.022 0.13 -10000 0 -0.3 47 47
CYLD 0.038 0.011 -10000 0 0 46 46
IKK complex/PKC alpha 0.023 0.13 -10000 0 -0.32 39 39
Regulation of Androgen receptor activity

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
HDAC1 -0.018 0.007 -10000 0 -10000 0 0
SMARCC1 -0.01 0.17 -10000 0 -1.1 12 12
REL 0.039 0.007 -10000 0 0 15 15
HDAC7 -0.049 0.088 0.17 7 -0.22 73 80
JUN 0.036 0.014 -10000 0 0 76 76
EP300 0.036 0.014 -10000 0 0 69 69
KAT2B 0 0 -10000 0 -10000 0 0
KAT5 0 0 -10000 0 -10000 0 0
MAPK14 -0.014 0.018 0.038 6 -0.053 1 7
FOXO1 0 0 -10000 0 -10000 0 0
T-DHT/AR -0.005 0.12 0.26 2 -0.22 86 88
MAP2K6 0.028 0.025 -10000 0 -0.012 146 146
BRM/BAF57 0.031 0.06 -10000 0 -0.13 55 55
MAP2K4 0.03 0.024 -10000 0 -0.015 115 115
SMARCA2 0.032 0.018 -10000 0 -10000 0 0
PDE9A -0.087 0.32 -10000 0 -0.83 82 82
NCOA2 0.037 0.013 -10000 0 0 60 60
CEBPA 0.037 0.012 -10000 0 0 54 54
EHMT2 0.041 0.007 -10000 0 0 14 14
cell proliferation -0.024 0.12 0.28 10 -0.31 36 46
NR0B1 0.038 0.01 -10000 0 0 38 38
EGR1 0.027 0.02 -10000 0 0 188 188
RXRs/9cRA 0.063 0.035 -10000 0 -0.1 3 3
AR/RACK1/Src -0.018 0.087 0.21 24 -0.22 21 45
AR/GR -0.014 0.091 0.2 2 -0.19 85 87
GNB2L1 0.039 0.009 -10000 0 0 30 30
PKN1 0.034 0.016 -10000 0 0 96 96
RCHY1 0.036 0.014 -10000 0 0 67 67
epidermal growth factor receptor activity 0 0 -10000 0 -10000 0 0
MAPK8 -0.014 0.02 0.042 4 -0.06 2 6
T-DHT/AR/TIF2/CARM1 0.002 0.085 0.23 2 -0.22 24 26
SRC -0.021 0.058 0.17 29 -0.15 7 36
NR3C1 0.038 0.011 -10000 0 0 42 42
KLK3 0.003 0.074 -10000 0 -10000 0 0
APPBP2 0.029 0.027 -10000 0 -0.033 67 67
TRIM24 0.039 0.011 -10000 0 0 39 39
T-DHT/AR/TIP60 -0.035 0.059 0.075 3 -0.16 59 62
TMPRSS2 0.014 0.1 -10000 0 -0.55 10 10
RXRG 0.035 0.015 -10000 0 0 81 81
mol:9cRA 0 0 -10000 0 -10000 0 0
RXRA 0.038 0.011 -10000 0 0 43 43
RXRB 0.041 0.005 -10000 0 0 8 8
CARM1 0.036 0.014 -10000 0 0 71 71
NR2C2 0.04 0.007 -10000 0 0 14 14
KLK2 -0.006 0.071 0.22 1 -0.28 8 9
AR -0.019 0.074 0.14 5 -0.19 65 70
SENP1 0.04 0.008 -10000 0 0 19 19
HSP90AA1 0 0 -10000 0 -10000 0 0
MDM2 0.037 0.01 -10000 0 0 36 36
SRY 0.04 0.002 -10000 0 0 2 2
GATA2 0.039 0.01 -10000 0 0 31 31
MYST2 0.04 0.008 -10000 0 0 20 20
HOXB13 0.039 0.011 -10000 0 -10000 0 0
T-DHT/AR/RACK1/Src -0.019 0.088 0.21 24 -0.23 21 45
positive regulation of transcription 0.039 0.01 -10000 0 0 31 31
DNAJA1 0.03 0.026 -10000 0 -0.033 67 67
proteasomal ubiquitin-dependent protein catabolic process -0.008 0.083 -10000 0 -0.26 49 49
NCOA1 0.042 0.032 0.12 1 -0.18 10 11
SPDEF 0.037 0.014 -10000 0 0 72 72
T-DHT/AR/TIF2 -0.017 0.093 0.2 5 -0.26 43 48
T-DHT/AR/Hsp90 -0.035 0.059 0.076 3 -0.16 59 62
GSK3B 0.039 0.008 -10000 0 0 23 23
NR2C1 0.038 0.01 -10000 0 0 33 33
mol:T-DHT -0.025 0.046 0.19 6 -0.16 8 14
SIRT1 0.04 0.007 -10000 0 0 16 16
ZMIZ2 -0.001 0.001 -10000 0 -0.012 1 1
POU2F1 0.032 0.057 0.12 2 -0.11 73 75
T-DHT/AR/DAX-1 -0.026 0.076 0.2 11 -0.21 25 36
CREBBP 0.037 0.012 -10000 0 0 53 53
SMARCE1 0.039 0.01 -10000 0 0 35 35
EGFR-dependent Endothelin signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
HRAS 0.039 0.01 -10000 0 0 31 31
EGFR 0.036 0.014 -10000 0 0 67 67
EGF/EGFR 0.046 0.057 -10000 0 -0.1 51 51
EGF/EGFR dimer/SHC/GRB2/SOS1 0.081 0.075 -10000 0 -0.11 49 49
mol:GTP 0 0 -10000 0 -10000 0 0
EDNRA 0.036 0.014 -10000 0 0 75 75
response to oxidative stress 0 0 -10000 0 -10000 0 0
EGF 0.038 0.01 -10000 0 0 38 38
EGF/EGFR dimer/SHC 0.059 0.054 -10000 0 -0.12 34 34
mol:GDP 0.073 0.071 -10000 0 -0.11 49 49
mol:Ca2+ 0 0 -10000 0 -10000 0 0
EDN1 0.034 0.015 -10000 0 0 89 89
GRB2/SOS1 0.047 0.044 -10000 0 -0.14 24 24
HRAS/GTP 0.048 0.06 -10000 0 -0.11 49 49
SHC1 0.039 0.008 -10000 0 0 23 23
HRAS/GDP 0.068 0.072 -10000 0 -0.11 46 46
FRAP1 -0.016 0.074 0.2 39 -0.18 4 43
EGF/EGFR dimer 0.041 0.05 -10000 0 -0.13 35 35
SOS1 0.037 0.012 -10000 0 0 51 51
GRB2 0.04 0.008 -10000 0 0 21 21
ETA receptor/Endothelin-1 0.038 0.046 -10000 0 -0.14 24 24
PDGFR-beta 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
S1P1/Sphingosine-1-phosphate 0.058 0.1 0.3 20 -0.26 15 35
PDGFB-D/PDGFRB/SLAP 0.033 0.038 -10000 0 -0.13 10 10
PDGFB-D/PDGFRB/APS/CBL 0.047 0.024 -10000 0 -0.11 4 4
AKT1 0.033 0.11 0.25 53 -0.18 1 54
mol:PI-4-5-P2 0 0.001 -10000 0 -10000 0 0
mol:Sphingosine-1-phosphate 0.043 0.095 0.27 18 -0.3 13 31
PIK3CA 0.029 0.019 -10000 0 0 166 166
FGR 0.022 0.09 0.23 17 -0.39 12 29
mol:Ca2+ 0.025 0.09 0.25 15 -0.34 13 28
MYC 0.001 0.28 0.33 23 -0.66 71 94
SHC1 0.039 0.008 -10000 0 0 23 23
HRAS/GDP 0.039 0.057 0.18 43 -0.1 12 55
LRP1/PDGFRB/PDGFB 0.053 0.056 -10000 0 -0.12 35 35
GRB10 0.04 0.008 -10000 0 0 22 22
PTPN11 0.039 0.009 -10000 0 0 29 29
GO:0007205 0.024 0.09 0.25 15 -0.34 13 28
PTEN 0.038 0.01 -10000 0 0 36 36
GRB2 0.04 0.008 -10000 0 0 21 21
GRB7 0.037 0.013 -10000 0 0 57 57
PDGFB-D/PDGFRB/SHP2 0.046 0.042 -10000 0 -0.14 21 21
PDGFB-D/PDGFRB/GRB10 0.05 0.034 -10000 0 -0.15 9 9
cell cycle arrest 0.033 0.038 -10000 0 -0.13 10 10
HRAS 0.039 0.01 -10000 0 0 31 31
HIF1A 0.019 0.099 0.23 49 -0.2 5 54
GAB1 0.022 0.1 0.27 11 -0.28 24 35
mol:GTP 0 0 -10000 0 -10000 0 0
DNM2 0.024 0.11 0.25 44 -0.25 29 73
PDGFB-D/PDGFRB 0.055 0.051 -10000 0 -0.12 6 6
mol:GDP 0 0 -10000 0 -10000 0 0
PDGFB-D/PDGFRB/LMW-PTP 0.047 0.04 -10000 0 -0.13 18 18
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB 0.048 0.12 0.29 23 -0.24 40 63
positive regulation of MAPKKK cascade 0.046 0.042 -10000 0 -0.14 21 21
PIK3R1 0.034 0.016 -10000 0 0 99 99
mol:IP3 0.025 0.091 0.25 15 -0.35 13 28
E5 0 0.002 -10000 0 -10000 0 0
CSK 0.038 0.011 -10000 0 -0.005 29 29
PDGFB-D/PDGFRB/GRB7 0.046 0.036 -10000 0 -0.14 11 11
SHB 0.04 0.006 -10000 0 0 11 11
BLK -0.039 0.16 0.26 3 -0.37 91 94
PTPN2 0.039 0.014 -10000 0 -0.013 34 34
PDGFB-D/PDGFRB/SNX15 0.053 0.025 -10000 0 -0.14 3 3
BCAR1 0.036 0.013 -10000 0 0 65 65
VAV2 0.007 0.13 0.27 16 -0.31 51 67
CBL 0.04 0.008 -10000 0 0 20 20
PDGFB-D/PDGFRB/DEP1 0.046 0.04 -10000 0 -0.13 19 19
LCK 0.026 0.077 0.26 5 -0.36 7 12
PDGFRB 0.036 0.019 0.068 1 -0.006 81 82
ACP1 0.039 0.01 -10000 0 0 34 34
HCK 0.014 0.092 0.34 1 -0.47 12 13
ABL1 0.018 0.092 0.24 18 -0.23 24 42
PDGFB-D/PDGFRB/CBL 0.021 0.11 0.29 6 -0.31 25 31
PTPN1 0.035 0.017 -10000 0 -0.007 70 70
SNX15 0.041 0.004 -10000 0 0 6 6
STAT3 0.038 0.011 -10000 0 0 41 41
STAT1 0.034 0.016 -10000 0 0 102 102
cell proliferation 0.009 0.25 0.31 30 -0.59 71 101
SLA 0.028 0.019 -10000 0 0 179 179
actin cytoskeleton reorganization 0.008 0.093 0.22 62 -0.18 1 63
SRC 0.024 0.053 0.33 1 -10000 0 1
PI3K -0.026 0.036 -10000 0 -0.12 35 35
PDGFB-D/PDGFRB/GRB7/SHC 0.061 0.044 -10000 0 -0.12 12 12
SH2B2 0 0 -10000 0 -10000 0 0
PLCgamma1/SPHK1 0.043 0.097 0.28 17 -0.31 13 30
LYN -0.001 0.12 0.28 2 -0.42 31 33
LRP1 0.036 0.014 -10000 0 0 69 69
SOS1 0.037 0.012 -10000 0 0 51 51
STAT5B 0.039 0.009 -10000 0 0 27 27
STAT5A 0.038 0.01 -10000 0 0 36 36
NCK1-2/p130 Cas 0.073 0.074 -10000 0 -0.12 21 21
SPHK1 0.041 0.009 0.063 1 0 24 25
EDG1 0.042 0.007 0.063 1 0 11 12
mol:DAG 0.025 0.091 0.25 15 -0.35 13 28
PLCG1 0.024 0.092 0.25 15 -0.36 13 28
NHERF/PDGFRB 0.057 0.049 -10000 0 -0.12 19 19
YES1 0.003 0.12 0.26 5 -0.43 30 35
cell migration 0.056 0.049 -10000 0 -0.12 19 19
SHC/Grb2/SOS1 0.083 0.071 -10000 0 -0.13 21 21
SLC9A3R2 0.037 0.012 -10000 0 0 54 54
SLC9A3R1 0.038 0.012 -10000 0 0 49 49
NHERF1-2/PDGFRB/PTEN 0.075 0.058 -10000 0 -0.11 30 30
FYN -0.012 0.13 0.26 3 -0.39 48 51
DOK1 0.006 0.067 0.19 52 -10000 0 52
HRAS/GTP 0.029 0.007 -10000 0 -10000 0 0
PDGFB 0.037 0.012 -10000 0 0 54 54
RAC1 -0.032 0.24 0.29 10 -0.53 76 86
PRKCD 0.006 0.067 0.19 50 -10000 0 50
FER 0.006 0.066 0.19 50 -10000 0 50
MAPKKK cascade 0 0.083 0.24 32 -0.18 4 36
RASA1 0.006 0.065 0.19 48 -10000 0 48
NCK1 0.036 0.014 -10000 0 0 70 70
NCK2 0.041 0.004 -10000 0 0 6 6
p62DOK/Csk 0.054 0.056 0.19 54 -0.11 11 65
PDGFB-D/PDGFRB/SHB 0.052 0.026 -10000 0 -0.14 3 3
chemotaxis 0.019 0.091 0.24 18 -0.23 24 42
STAT1-3-5/STAT1-3-5 0.051 0.079 -10000 0 -0.12 52 52
Bovine Papilomavirus E5/PDGFRB 0.025 0.019 -10000 0 -0.035 24 24
PTPRJ 0.039 0.01 -10000 0 0 33 33
JNK signaling in the CD4+ TCR pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1 0.063 0.067 -10000 0 -0.11 44 44
MAP4K1 0.036 0.014 -10000 0 0 67 67
MAP3K8 0.039 0.008 -10000 0 0 24 24
PRKCB 0 0 -10000 0 -10000 0 0
DBNL 0.04 0.006 -10000 0 0 12 12
CRKL 0.038 0.01 -10000 0 0 36 36
MAP3K1 0.007 0.066 0.17 2 -0.18 45 47
JUN -0.004 0.11 -10000 0 -0.5 21 21
MAP3K7 0.008 0.067 0.2 5 -0.22 18 23
GRAP2 0.037 0.013 -10000 0 0 56 56
CRK 0.038 0.012 -10000 0 0 49 49
MAP2K4 0 0.083 0.17 7 -0.27 26 33
LAT 0.04 0.006 -10000 0 0 11 11
LCP2 0.034 0.016 -10000 0 0 101 101
MAPK8 0.001 0.11 -10000 0 -0.54 21 21
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family 0.019 0.068 -10000 0 -0.16 49 49
LAT/GRAP2/SLP76/HPK1/HIP-55 0.072 0.077 -10000 0 -0.11 42 42
Insulin-mediated glucose transport

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
Insulin responsive Vesicles 0.017 0.14 0.26 3 -0.34 38 41
CaM/Ca2+ 0.028 0.016 -10000 0 -0.12 5 5
AKT1 0.039 0.01 -10000 0 0 34 34
AKT2 0.037 0.012 -10000 0 0 54 54
STXBP4 0.038 0.011 -10000 0 0 43 43
mol:GTP 0 0 -10000 0 -10000 0 0
mol:glucose 0.004 0.14 0.25 3 -0.36 38 41
YWHAZ 0.034 0.016 -10000 0 0 96 96
CALM1 0.039 0.009 -10000 0 0 26 26
YWHAQ 0.04 0.007 -10000 0 0 18 18
TBC1D4 -0.018 0.007 -10000 0 -10000 0 0
mol:Ca2+ 0 0 -10000 0 -10000 0 0
YWHAH 0.038 0.011 -10000 0 0 46 46
YWHAB 0.038 0.011 -10000 0 0 45 45
SNARE/Synip 0.044 0.029 -10000 0 -0.11 9 9
YWHAG 0.039 0.009 -10000 0 0 25 25
ASIP 0.038 0.011 -10000 0 0 46 46
PRKCI 0.027 0.02 -10000 0 0 192 192
AS160/CaM/Ca2+ 0.028 0.016 -10000 0 -0.12 5 5
RHOQ 0.039 0.009 -10000 0 0 25 25
GYS1 0.007 0.021 0.25 1 -0.17 5 6
PRKCZ 0.039 0.009 -10000 0 0 27 27
TRIP10 0.038 0.012 -10000 0 0 49 49
TC10/GTP/CIP4/Exocyst 0.046 0.029 -10000 0 -0.11 12 12
AS160/14-3-3 0.014 0.083 0.19 3 -0.27 23 26
VAMP2 0.036 0.014 -10000 0 0 69 69
SLC2A4 0.001 0.15 0.27 2 -0.4 38 40
STX4 0 0 -10000 0 -10000 0 0
GSK3B 0.022 0.024 -10000 0 -0.2 5 5
SFN 0.035 0.015 -10000 0 0 83 83
LNPEP 0.035 0.014 -10000 0 0 77 77
YWHAE 0.037 0.013 -10000 0 0 58 58
mTOR signaling pathway

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
GBL 0.039 0.009 -10000 0 0 26 26
MKNK1 0.04 0.007 -10000 0 0 15 15
mol:PIP3 -0.013 0.037 0.14 2 -0.16 15 17
FRAP1 0.028 0.11 -10000 0 -0.42 23 23
AKT1 0.023 0.086 0.17 112 -0.17 10 122
INSR 0.038 0.012 -10000 0 0 49 49
Insulin Receptor/Insulin 0.047 0.023 -10000 0 -0.11 4 4
mol:GTP 0.054 0.092 0.24 31 -0.16 11 42
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit -0.006 0.053 -10000 0 -0.18 30 30
TSC2 0.039 0.01 -10000 0 0 35 35
RHEB/GDP 0.03 0.069 0.16 6 -0.16 15 21
TSC1 0.039 0.01 -10000 0 0 31 31
Insulin Receptor/IRS1 0.034 0.031 -10000 0 -0.23 6 6
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA 0.016 0.074 0.19 1 -0.22 28 29
mol:GDP 0 0 -10000 0 -10000 0 0
EIF3A 0 0 -10000 0 -10000 0 0
RPS6KB1 0.032 0.11 0.24 20 -0.33 26 46
MAP3K5 -0.006 0.061 0.19 5 -0.22 37 42
PIK3R1 0.034 0.016 -10000 0 0 99 99
apoptosis -0.006 0.061 0.19 5 -0.22 37 42
mol:LY294002 0 0 0.001 3 -0.001 6 9
EIF4B 0.028 0.1 0.25 16 -0.3 26 42
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3 0.04 0.1 0.23 16 -0.27 29 45
eIF4E/eIF4G1/eIF4A1 0.012 0.065 -10000 0 -0.26 21 21
KIAA1303 0 0 -10000 0 -10000 0 0
PI3K 0.027 0.052 -10000 0 -0.15 18 18
mTOR/RHEB/GTP/Raptor/GBL 0.028 0.077 0.2 20 -0.18 23 43
FKBP1A 0.038 0.011 -10000 0 0 44 44
RHEB/GTP 0.052 0.087 0.23 19 -0.16 14 33
mol:Amino Acids 0 0 0.001 3 -0.001 6 9
FKBP12/Rapamycin 0.028 0.013 -10000 0 -0.13 2 2
PDPK1 0.01 0.077 0.16 99 -0.17 11 110
EIF4E 0.039 0.01 -10000 0 0 31 31
ASK1/PP5C 0.02 0.19 -10000 0 -0.56 43 43
mTOR/RHEB/GTP/Raptor/GBL/eIF4E 0.005 0.11 -10000 0 -0.56 10 10
TSC1/TSC2 0.059 0.099 0.26 31 -0.17 11 42
tumor necrosis factor receptor activity 0 0 0.001 6 -0.001 3 9
RPS6 0.039 0.01 -10000 0 0 32 32
PPP5C 0.039 0.009 -10000 0 0 27 27
EIF4G1 0.032 0.017 -10000 0 0 116 116
IRS1 0.011 0.028 -10000 0 -0.24 6 6
INS 0.039 0.009 -10000 0 0 30 30
PTEN 0.038 0.01 -10000 0 0 36 36
PDK2 0.012 0.077 0.16 100 -0.17 10 110
EIF4EBP1 -0.036 0.27 -10000 0 -1.1 35 35
PIK3CA 0.029 0.019 -10000 0 0 166 166
PPP2R5D 0.028 0.1 0.28 4 -0.38 22 26
peptide biosynthetic process -0.014 0.029 0.19 9 -10000 0 9
RHEB 0.037 0.012 -10000 0 0 53 53
EIF4A1 0.038 0.011 -10000 0 0 42 42
mol:Rapamycin 0 0.001 0.003 51 -0.002 3 54
EEF2 -0.014 0.03 0.19 9 -10000 0 9
eIF4E/4E-BP1 -0.016 0.26 -10000 0 -0.99 35 35
FOXA2 and FOXA3 transcription factor networks

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
ACADVL -0.041 0.25 0.48 1 -0.54 64 65
PCK1 -0.11 0.41 -10000 0 -1 78 78
HNF4A -0.077 0.35 0.6 2 -0.76 89 91
KCNJ11 -0.008 0.23 -10000 0 -0.52 37 37
AKT1 0.005 0.17 -10000 0 -0.32 42 42
response to starvation -0.015 0.043 -10000 0 -0.11 75 75
DLK1 -0.002 0.24 0.64 3 -0.53 35 38
NKX2-1 -0.002 0.15 0.35 3 -0.3 40 43
ACADM -0.055 0.27 0.54 1 -0.59 69 70
TAT -0.024 0.18 -10000 0 -0.53 17 17
CEBPB 0.039 0.017 -10000 0 -0.072 2 2
CEBPA 0.042 0.016 -10000 0 -0.069 2 2
TTR 0.035 0.17 0.62 2 -0.82 4 6
PKLR -0.028 0.24 0.48 4 -0.55 45 49
APOA1 -0.13 0.48 -10000 0 -1.1 95 95
CPT1C -0.036 0.24 -10000 0 -0.56 49 49
ALAS1 -0.005 0.16 -10000 0 -0.8 3 3
TFRC -0.063 0.36 -10000 0 -0.86 75 75
FOXF1 0.034 0.015 -10000 0 -10000 0 0
NF1 0.038 0.02 -10000 0 -0.16 1 1
HNF1A (dimer) 0.009 0.001 -10000 0 -10000 0 0
CPT1A -0.046 0.26 0.54 1 -0.57 66 67
HMGCS1 -0.034 0.26 0.5 3 -0.58 57 60
NR3C1 0.048 0.014 -10000 0 -10000 0 0
CPT1B -0.034 0.23 -10000 0 -0.57 42 42
chromatin remodeling 0 0 -10000 0 -10000 0 0
SP1 0.04 0.007 -10000 0 -10000 0 0
GCK -0.036 0.24 0.46 1 -0.56 48 49
CREB1 0.019 0.095 -10000 0 -0.21 77 77
IGFBP1 -0.004 0.15 -10000 0 -0.49 4 4
PDX1 0.009 0.14 0.4 1 -0.29 28 29
UCP2 -0.062 0.3 0.48 5 -0.65 81 86
ALDOB -0.007 0.23 -10000 0 -0.52 37 37
AFP 0.015 0.049 -10000 0 -10000 0 0
BDH1 -0.024 0.29 0.48 13 -0.6 64 77
HADH -0.008 0.23 -10000 0 -0.47 57 57
F2 -0.038 0.31 -10000 0 -0.74 37 37
HNF1A 0.009 0.001 -10000 0 -10000 0 0
G6PC 0.021 0.087 -10000 0 -10000 0 0
SLC2A2 0.028 0.16 -10000 0 -0.43 1 1
INS 0.029 0.013 0.18 1 -10000 0 1
FOXA1 0.055 0.016 -10000 0 -10000 0 0
FOXA3 0.019 0.12 -10000 0 -0.2 114 114
FOXA2 0.01 0.29 -10000 0 -0.56 54 54
ABCC8 -0.008 0.23 -10000 0 -0.52 37 37
ALB 0.015 0.049 -10000 0 -10000 0 0
S1P5 pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
mol:S1P 0 0 -10000 0 -10000 0 0
telencephalon oligodendrocyte cell migration -0.008 0.084 0.17 72 -10000 0 72
GNAI2 0.04 0.006 -10000 0 0 13 13
S1P/S1P5/G12 0.026 0.007 -10000 0 -10000 0 0
mol:GDP 0 0 -10000 0 -10000 0 0
GNAO1 0.035 0.015 -10000 0 0 85 85
RhoA/GTP 0.008 0.085 -10000 0 -0.17 72 72
negative regulation of cAMP metabolic process -0.008 0.078 -10000 0 -0.18 69 69
GNAZ 0.038 0.011 -10000 0 0 46 46
GNAI3 0.038 0.011 -10000 0 0 45 45
GNA12 0.039 0.01 -10000 0 0 33 33
S1PR5 0 0 -10000 0 -10000 0 0
mol:GTP 0 0 -10000 0 -10000 0 0
S1P/S1P5/Gi -0.008 0.078 -10000 0 -0.18 69 69
RhoA/GDP 0.029 0.014 -10000 0 -0.12 4 4
RHOA 0.04 0.006 -10000 0 0 13 13
GNAI1 0.034 0.015 -10000 0 0 93 93
Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CRKL 0.038 0.01 -10000 0 0 36 36
RAS family/GTP/Tiam1 0.011 0.059 -10000 0 -0.16 38 38
NT3 (dimer)/TRKC 0.041 0.034 -10000 0 -0.13 7 7
NT3 (dimer)/TRKB 0.056 0.043 -10000 0 -0.12 8 8
SHC/Grb2/SOS1/GAB1/PI3K -0.002 0.079 -10000 0 -0.2 56 56
RAPGEF1 0.039 0.009 -10000 0 0 26 26
BDNF 0.04 0.006 -10000 0 0 12 12
PIK3CA 0.029 0.019 -10000 0 0 166 166
DYNLT1 0.036 0.014 -10000 0 0 75 75
NTRK1 0.04 0.007 -10000 0 0 16 16
NTRK2 0.039 0.01 -10000 0 0 35 35
NTRK3 0.038 0.011 -10000 0 0 45 45
NT-4/5 (dimer)/TRKB 0.05 0.017 -10000 0 -0.085 1 1
neuron apoptosis -0.031 0.099 0.25 27 -0.23 2 29
SHC 2-3/Grb2 0.032 0.1 0.24 2 -0.26 27 29
SHC1 0.039 0.008 -10000 0 0 23 23
SHC2 0.006 0.12 0.21 2 -0.35 47 49
SHC3 0.03 0.083 0.21 2 -0.4 13 15
STAT3 (dimer) 0.001 0.11 -10000 0 -0.26 79 79
NT3 (dimer)/TRKA 0.057 0.043 -10000 0 -0.12 8 8
RIN/GDP 0.044 0.083 0.22 18 -0.2 22 40
GIPC1 0.034 0.015 -10000 0 0 92 92
KRAS 0.034 0.016 -10000 0 0 95 95
DNAJA3 0.013 0.052 0.14 13 -0.15 10 23
RIN/GTP 0.028 0.008 -10000 0 -10000 0 0
CCND1 -0.054 0.18 -10000 0 -0.49 79 79
MAGED1 0.039 0.008 -10000 0 0 24 24
PTPN11 0.039 0.009 -10000 0 0 29 29
RICS 0.036 0.014 -10000 0 0 70 70
NT-4/5 (dimer) 0 0 -10000 0 -10000 0 0
SHC/GRB2/SOS1 0.065 0.049 -10000 0 -0.12 24 24
GRB2 0.04 0.008 -10000 0 0 21 21
NGF (dimer)/TRKA/MATK 0.049 0.018 -10000 0 -10000 0 0
TRKA/NEDD4-2 0.047 0.038 -10000 0 -0.13 17 17
ELMO1 0.036 0.014 -10000 0 0 75 75
RhoG/GTP/ELMO1/DOCK1 0.035 0.046 -10000 0 -0.11 41 41
NGF 0 0 -10000 0 -10000 0 0
HRAS 0.039 0.01 -10000 0 0 31 31
DOCK1 0.037 0.012 -10000 0 0 53 53
GAB2 0.031 0.018 -10000 0 0 136 136
RIT2 0.038 0.01 -10000 0 0 37 37
RIT1 0.037 0.012 -10000 0 0 50 50
FRS2 0.038 0.011 -10000 0 0 41 41
DNM1 0.039 0.01 -10000 0 0 33 33
mol:GTP 0 0 -10000 0 -10000 0 0
CRK 0.038 0.012 -10000 0 0 49 49
SH2B1 (homopentamer) 0 0 -10000 0 -10000 0 0
RhoG/GTP 0.031 0.06 0.17 9 -0.15 9 18
mol:GDP 0.039 0.11 0.26 16 -0.3 23 39
NGF (dimer) 0 0 -10000 0 -10000 0 0
RhoG/GDP 0.022 0.029 -10000 0 -0.12 18 18
RIT1/GDP 0.041 0.083 0.21 14 -0.21 24 38
TIAM1 0.036 0.013 -10000 0 0 66 66
PIK3R1 0.034 0.016 -10000 0 0 99 99
BDNF (dimer)/TRKB 0.072 0.03 -10000 0 -0.12 1 1
KIDINS220/CRKL/C3G 0.055 0.019 -10000 0 -10000 0 0
SHC/RasGAP 0.048 0.038 -10000 0 -0.13 18 18
FRS2 family/SHP2 0.065 0.049 -10000 0 -0.12 25 25
SHC/GRB2/SOS1/GAB1 0.076 0.061 -10000 0 -0.12 31 31
RIT1/GTP 0.024 0.026 -10000 0 -0.12 15 15
NT3 (dimer) 0.031 0.018 -10000 0 0 133 133
RAP1/GDP 0.03 0.073 0.18 9 -0.18 26 35
KIDINS220/CRKL 0.038 0.01 -10000 0 0 36 36
BDNF (dimer) 0.04 0.006 -10000 0 0 12 12
ubiquitin-dependent protein catabolic process 0.043 0.033 -10000 0 -0.11 17 17
Schwann cell development -0.007 0.011 -10000 0 -0.044 11 11
EHD4 0.039 0.01 -10000 0 0 35 35
FRS2 family/GRB2/SOS1 0.079 0.059 -10000 0 -0.12 28 28
FRS2 family/SHP2/CRK family/C3G/GAB2 0.003 0.081 -10000 0 -0.21 38 38
RAP1B 0.037 0.012 -10000 0 0 54 54
RAP1A 0.039 0.01 -10000 0 0 35 35
CDC42/GTP 0.067 0.051 0.2 2 -0.11 9 11
ABL1 0.039 0.01 -10000 0 0 32 32
SH2B family/GRB2/SOS1 0.047 0.044 -10000 0 -0.14 24 24
Rap1/GTP 0.005 0.11 -10000 0 -0.27 52 52
STAT3 0.001 0.11 -10000 0 -0.26 79 79
axon guidance 0.041 0.036 -10000 0 -0.11 9 9
MAPK3 -0.014 0.031 0.19 11 -10000 0 11
MAPK1 -0.013 0.032 0.19 12 -10000 0 12
CDC42/GDP 0.046 0.086 0.22 21 -0.2 24 45
NTF3 0.031 0.018 -10000 0 0 133 133
NTF4 0 0 -10000 0 -10000 0 0
NGF (dimer)/TRKA/FAIM 0.05 0.019 -10000 0 -0.11 2 2
PI3K 0.023 0.06 -10000 0 -0.15 44 44
FRS3 0.04 0.008 -10000 0 0 21 21
FAIM 0.038 0.011 -10000 0 0 43 43
GAB1 0.037 0.013 -10000 0 0 58 58
RASGRF1 0.013 0.052 0.14 13 -0.15 10 23
SOS1 0.037 0.012 -10000 0 0 51 51
MCF2L 0.004 0.058 0.18 35 -0.12 7 42
RGS19 0.037 0.013 -10000 0 0 59 59
CDC42 0.04 0.007 -10000 0 0 18 18
RAS family/GTP 0.033 0.12 0.29 3 -0.35 29 32
Rac1/GDP 0.045 0.085 0.22 21 -0.2 24 45
NGF (dimer)/TRKA/GRIT 0.043 0.034 -10000 0 -0.11 19 19
neuron projection morphogenesis -0.048 0.24 -10000 0 -0.83 39 39
NGF (dimer)/TRKA/NEDD4-2 0.043 0.033 -10000 0 -0.11 17 17
MAP2K1 -0.007 0.079 0.2 58 -0.18 3 61
NGFR 0.039 0.009 -10000 0 0 25 25
NGF (dimer)/TRKA/GIPC/GAIP 0.015 0.041 -10000 0 -0.15 23 23
RAS family/GTP/PI3K -0.005 0.07 -10000 0 -0.19 49 49
FRS2 family/SHP2/GRB2/SOS1 0.087 0.074 -10000 0 -0.13 38 38
NRAS 0.039 0.009 -10000 0 0 30 30
GRB2/SOS1 0.047 0.044 -10000 0 -0.14 24 24
PRKCI 0.027 0.02 -10000 0 0 192 192
ChemicalAbstracts:146-91-8 0 0 -10000 0 -10000 0 0
RAC1 0.039 0.009 -10000 0 0 28 28
PRKCZ 0.039 0.009 -10000 0 0 27 27
MAPKKK cascade 0.026 0.049 -10000 0 -0.5 2 2
RASA1 0.037 0.013 -10000 0 0 56 56
TRKA/c-Abl 0.053 0.031 -10000 0 -0.13 11 11
SQSTM1 0.038 0.011 -10000 0 0 46 46
BDNF (dimer)/TRKB/GIPC 0.07 0.059 -10000 0 -0.11 23 23
NGF (dimer)/TRKA/p62/Atypical PKCs 0.045 0.068 -10000 0 -0.11 54 54
MATK 0.037 0.013 -10000 0 0 56 56
NEDD4L 0.036 0.014 -10000 0 0 74 74
RAS family/GDP -0.01 0.039 -10000 0 -0.14 24 24
NGF (dimer)/TRKA 0.004 0.04 0.16 6 -0.15 10 16
Rac1/GTP -0.003 0.049 -10000 0 -0.15 14 14
FRS2 family/SHP2/CRK family 0.087 0.067 -10000 0 -0.12 23 23
Aurora A signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
Aurora A/GADD45A 0.04 0.039 0.17 2 -0.15 10 12
BIRC5 0.037 0.012 -10000 0 0 52 52
NFKBIA -0.004 0.027 0.25 1 -0.18 5 6
CPEB1 0.039 0.009 -10000 0 0 28 28
AKT1 -0.002 0.041 0.26 9 -0.17 6 15
NDEL1 0.038 0.011 -10000 0 0 40 40
Aurora A/BRCA1 0.026 0.048 0.15 2 -0.098 52 54
NDEL1/TACC3 0.045 0.051 0.17 1 -0.11 30 31
GADD45A 0.036 0.013 -10000 0 0 66 66
GSK3B 0.038 0.012 0.091 14 0 23 37
PAK1/Aurora A 0.041 0.039 0.17 2 -0.16 9 11
MDM2 0.038 0.01 -10000 0 0 36 36
JUB 0.037 0.013 -10000 0 0 62 62
TPX2 -0.015 0.009 -10000 0 -10000 0 0
TP53 -0.045 0.12 0.16 1 -0.24 134 135
DLG7 -0.002 0.026 0.25 1 -0.17 3 4
AURKAIP1 0 0 -10000 0 -10000 0 0
ARHGEF7 0.039 0.009 -10000 0 0 28 28
G2 phase of mitotic cell cycle 0 0 -10000 0 -10000 0 0
Aurora A/NDEL1/TACC3 0.047 0.054 0.18 1 -0.12 30 31
G2/M transition of mitotic cell cycle 0.026 0.048 0.15 2 -0.098 52 54
AURKA 0.01 0.029 0.13 12 -0.2 6 18
AURKB -0.002 0.063 -10000 0 -0.19 49 49
CDC25B 0.005 0.047 -10000 0 -0.22 19 19
G2/M transition checkpoint 0.032 0.043 0.15 2 -0.11 31 33
mRNA polyadenylation 0.038 0.033 0.15 2 -0.13 10 12
Aurora A/CPEB 0.039 0.034 0.15 2 -0.13 10 12
Aurora A/TACC1/TRAP/chTOG 0.051 0.073 -10000 0 -0.17 14 14
BRCA1 0.034 0.015 -10000 0 0 93 93
centrosome duplication 0.041 0.039 0.17 2 -0.16 9 11
regulation of centrosome cycle 0.044 0.05 0.17 1 -0.11 30 31
spindle assembly 0.049 0.072 -10000 0 -0.17 14 14
TDRD7 0.034 0.015 -10000 0 0 89 89
Aurora A/RasGAP/Survivin 0.044 0.071 0.19 1 -0.16 8 9
CENPA 0.009 0.053 -10000 0 -0.32 11 11
Aurora A/PP2A 0.044 0.038 0.17 2 -0.15 10 12
meiosis 0 0 -10000 0 -10000 0 0
protein catabolic process -0.013 0.057 0.17 4 -0.2 14 18
negative regulation of DNA binding -0.046 0.12 0.16 1 -0.24 137 138
prophase 0 0 -10000 0 -10000 0 0
GIT1/beta-PIX 0.055 0.018 -10000 0 -10000 0 0
RASA1 0.037 0.013 -10000 0 0 56 56
Ajuba/Aurora A 0.032 0.043 0.15 2 -0.11 31 33
mitotic prometaphase 0.004 0.025 0.073 62 -10000 0 62
proteasomal ubiquitin-dependent protein catabolic process 0.01 0.029 0.13 12 -0.2 6 18
TACC1 0.035 0.015 -10000 0 0 86 86
TACC3 0.033 0.016 -10000 0 0 103 103
Aurora A/Antizyme1 0.029 0.043 0.15 1 -0.1 34 35
Aurora A/RasGAP 0.041 0.04 0.17 2 -0.16 10 12
OAZ1 0.033 0.016 -10000 0 0 105 105
RAN 0.04 0.008 -10000 0 0 21 21
mitosis 0 0 -10000 0 -10000 0 0
PRKACA 0.034 0.016 0.091 12 0 84 96
GIT1 0.039 0.009 -10000 0 0 25 25
GIT1/beta-PIX/PAK1 0.064 0.044 -10000 0 -0.12 16 16
Importin alpha/Importin beta/TPX2 -0.015 0.009 -10000 0 -10000 0 0
PPP2R5D 0.039 0.009 -10000 0 0 26 26
Aurora A/TPX2 0.017 0.034 0.15 1 -0.17 10 11
PAK1 0.036 0.013 -10000 0 0 65 65
CKAP5 0.038 0.011 -10000 0 0 45 45
p38 MAPK signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
TRAF6/ASK1 0.019 0.052 -10000 0 -0.13 47 47
TRAF2/ASK1 0.044 0.033 -10000 0 -0.11 18 18
ATM 0.036 0.014 -10000 0 0 69 69
MAP2K3 -0.029 0.15 -10000 0 -0.33 84 84
response to stress 0 0 -10000 0 -10000 0 0
MAP2K6 -0.035 0.14 0.21 2 -0.33 65 67
hyperosmotic response 0 0 -10000 0 -10000 0 0
response to oxidative stress 0 0 -10000 0 -10000 0 0
GADD45G 0.037 0.013 -10000 0 0 58 58
TXN 0.009 0.003 -10000 0 -10000 0 0
CALM1 0.039 0.009 -10000 0 0 26 26
GADD45A 0.036 0.013 -10000 0 0 66 66
GADD45B 0.034 0.015 -10000 0 0 92 92
MAP3K1 0.036 0.013 -10000 0 0 63 63
MAP3K6 0.04 0.008 -10000 0 0 19 19
MAP3K7 0.038 0.01 -10000 0 0 38 38
MAP3K4 0.038 0.011 -10000 0 0 43 43
mol:Ca2+ 0 0 -10000 0 -10000 0 0
ASK1/ASK2 0.048 0.039 -10000 0 -0.13 19 19
TAK1/TAB family 0.016 0.07 0.17 2 -0.28 21 23
RAC1/OSM/MEKK3 0.073 0.023 -10000 0 -0.1 1 1
TRAF2 0.039 0.01 -10000 0 0 32 32
RAC1/OSM/MEKK3/MKK3 0.002 0.14 -10000 0 -0.27 81 81
TRAF6 0.008 0.044 -10000 0 -0.2 24 24
RAC1 0.039 0.009 -10000 0 0 28 28
mol:LPS 0 0 -10000 0 -10000 0 0
CAMK2B 0.041 0.005 -10000 0 0 9 9
CCM2 0.041 0.005 -10000 0 0 9 9
CaM/Ca2+/CAMKIIB 0.052 0.017 -10000 0 -0.11 3 3
MAPK11 0.029 0.019 -10000 0 0 157 157
response to DNA damage stimulus 0 0 -10000 0 -10000 0 0
CaM/Ca2+/CAMKIIB/ASK1 0.063 0.042 -10000 0 -0.1 21 21
OSM/MEKK3 0.059 0.012 -10000 0 -10000 0 0
TAOK1 0.004 0.052 -10000 0 -0.2 34 34
TAOK2 0.004 0.052 -10000 0 -0.2 34 34
TAOK3 0.001 0.058 -10000 0 -0.2 43 43
MAP3K7IP1 0.037 0.012 -10000 0 0 51 51
MAPK14 0.04 0.008 -10000 0 0 20 20
MAP3K7IP2 0.037 0.012 -10000 0 0 53 53
MAP3K5 0.037 0.013 -10000 0 0 60 60
MAP3K10 0.037 0.013 -10000 0 0 57 57
MAP3K3 0.04 0.007 -10000 0 0 14 14
TRX/ASK1 0.022 0.047 -10000 0 -0.15 34 34
GADD45/MTK1/MTK1 0.056 0.066 -10000 0 -0.1 55 55
Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
DYNC1H1 0.038 0.01 -10000 0 0 37 37
VLDLR 0.032 0.017 -10000 0 0 121 121
LRPAP1 0.036 0.014 -10000 0 0 72 72
NUDC 0.039 0.009 -10000 0 0 25 25
RELN/LRP8 0.05 0.054 -10000 0 -0.12 29 29
CaM/Ca2+ 0.028 0.016 -10000 0 -0.12 5 5
KATNA1 0.037 0.012 -10000 0 0 51 51
GO:0030286 0 0 -10000 0 -10000 0 0
ABL1 -0.006 0.059 0.19 24 -0.19 1 25
IQGAP1/CaM 0.041 0.054 -10000 0 -0.14 43 43
DAB1 0.04 0.008 -10000 0 0 21 21
IQGAP1 0.036 0.013 -10000 0 0 66 66
PLA2G7 0.03 0.018 -10000 0 0 149 149
CALM1 0.039 0.009 -10000 0 0 26 26
DYNLT1 0.036 0.014 -10000 0 0 75 75
mol:Ca2+ 0 0 -10000 0 -10000 0 0
LRPAP1/LRP8 0.041 0.051 -10000 0 -0.14 35 35
UniProt:Q4QZ09 0 0 -10000 0 -10000 0 0
CLIP1 0 0 -10000 0 -10000 0 0
CDK5R1 0.038 0.011 -10000 0 0 40 40
LIS1/Poliovirus Protein 3A -0.015 0.013 -10000 0 -0.13 5 5
CDK5R2 0.04 0.006 -10000 0 0 11 11
mol:PP1 0 0 -10000 0 -10000 0 0
RELN/VLDLR/DAB1 0.045 0.058 -10000 0 -0.12 38 38
YWHAE 0.037 0.013 -10000 0 0 58 58
NDEL1/14-3-3 E 0.028 0.076 0.25 25 -0.17 6 31
MAP1B -0.006 0.049 0.18 3 -0.18 36 39
RAC1 0.011 0.041 -10000 0 -0.58 1 1
p35/CDK5 -0.011 0.062 0.18 23 -0.18 1 24
RELN 0.034 0.016 -10000 0 0 96 96
PAFAH/LIS1 0.025 0.027 -10000 0 -0.15 5 5
LIS1/CLIP170 -0.015 0.013 -10000 0 -0.13 5 5
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain 0.02 0.075 0.19 8 -0.18 14 22
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3 -0.001 0.093 -10000 0 -0.22 60 60
GO:0005869 0 0 -10000 0 -10000 0 0
NDEL1 -0.001 0.069 0.21 32 -10000 0 32
LIS1/IQGAP1 0.03 0.026 -10000 0 -0.15 5 5
RHOA 0.011 0.043 0.12 18 -0.12 27 45
PAFAH1B1 -0.017 0.008 -10000 0 -10000 0 0
PAFAH1B3 0.034 0.016 -10000 0 0 94 94
PAFAH1B2 0.039 0.009 -10000 0 0 28 28
MAP1B/LIS1/Dynein heavy chain 0.014 0.059 0.18 1 -0.14 40 41
NDEL1/Katanin 60/Dynein heavy chain 0.034 0.084 0.28 15 -0.18 9 24
LRP8 0.039 0.01 -10000 0 0 35 35
NDEL1/Katanin 60 0.024 0.074 0.24 22 -0.17 10 32
P39/CDK5 -0.011 0.066 0.19 25 -0.18 1 26
LIS1/NudC/Dynein intermediate chain/microtubule organizing center 0.033 0.025 -10000 0 -0.15 5 5
CDK5 -0.012 0.05 0.18 16 -0.18 1 17
PPP2R5D 0.039 0.009 -10000 0 0 26 26
LIS1/CLIP170/Dynein Complex/Dynactin Complex -0.012 0.011 -10000 0 -0.1 5 5
CSNK2A1 0.038 0.012 -10000 0 0 47 47
RELN/VLDLR/DAB1/LIS1 0.055 0.064 0.2 19 -0.11 36 55
RELN/VLDLR 0.053 0.072 -10000 0 -0.11 60 60
CDC42 0.01 0.047 0.12 19 -0.12 32 51
Ceramide signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
SPHK2 -0.018 0.007 0 74 -10000 0 74
MAP4K4 -0.006 0.079 -10000 0 -0.24 31 31
BAG4 0.037 0.012 -10000 0 0 55 55
PKC zeta/ceramide 0.029 0.032 -10000 0 -0.18 8 8
NFKBIA 0.036 0.013 -10000 0 0 64 64
BIRC3 0.025 0.02 -10000 0 0 210 210
BAX 0.007 0.067 -10000 0 -0.34 19 19
RIPK1 0.039 0.01 -10000 0 0 32 32
AKT1 0.002 0.12 0.69 16 -10000 0 16
BAD -0.001 0.028 0.22 2 -0.18 7 9
SMPD1 0.008 0.059 0.16 14 -0.17 28 42
RB1 -0.003 0.043 0.2 8 -0.18 8 16
FADD/Caspase 8 -0.008 0.11 0.24 8 -0.3 43 51
MAP2K4 -0.007 0.028 -10000 0 -0.18 8 8
NSMAF 0.037 0.012 -10000 0 0 55 55
response to UV 0 0 -10000 0 -10000 0 0
RAF1 -0.003 0.042 0.18 15 -0.19 8 23
EGF 0.038 0.01 -10000 0 0 38 38
mol:ceramide 0.005 0.027 -10000 0 -0.19 8 8
MADD 0.041 0.005 -10000 0 0 9 9
response to oxidative stress 0 0 -10000 0 -10000 0 0
mol:Free Fatty acid -0.015 0.009 0 151 -10000 0 151
ASAH1 0.033 0.016 -10000 0 0 106 106
negative regulation of cell cycle -0.003 0.043 0.2 8 -0.18 8 16
cell proliferation 0.026 0.054 0.2 11 -0.21 6 17
BID -0.017 0.18 -10000 0 -0.65 36 36
MAP3K1 -0.002 0.027 -10000 0 -0.18 8 8
EIF2A 0.007 0.078 0.19 60 -0.22 8 68
TRADD 0.037 0.013 -10000 0 0 61 61
CRADD 0.04 0.006 -10000 0 0 10 10
MAPK3 -0.002 0.044 0.18 14 -0.21 6 20
response to heat 0 0 -10000 0 -10000 0 0
MAPK1 -0.007 0.048 0.18 13 -0.19 7 20
Cathepsin D/ceramide 0.028 0.032 -10000 0 -0.18 8 8
FADD -0.005 0.082 0.22 4 -0.24 32 36
KSR1 0 0.033 0.21 5 -0.18 8 13
MAPK8 0.002 0.053 -10000 0 -0.2 15 15
PRKRA 0.003 0.046 0.2 18 -0.18 8 26
PDGFA 0.037 0.013 -10000 0 0 57 57
TRAF2 0.039 0.01 -10000 0 0 32 32
IGF1 0.035 0.014 -10000 0 0 77 77
mol:GD3 0 0 -10000 0 -10000 0 0
ganglioside biosynthetic process 0.005 0.027 -10000 0 -0.19 8 8
CTSD 0.037 0.012 -10000 0 0 55 55
regulation of nitric oxide biosynthetic process 0.044 0.049 -10000 0 -0.13 34 34
response to radiation 0 0 -10000 0 -10000 0 0
ERK1/PKC delta 0.029 0.057 0.21 11 -0.22 6 17
PRKCD 0.037 0.012 -10000 0 0 51 51
PRKCZ 0.039 0.009 -10000 0 0 27 27
mol:GW4869 0 0 -10000 0 -10000 0 0
mol:sphingosine -0.015 0.009 0 151 -10000 0 151
RelA/NF kappa B1 0.044 0.049 -10000 0 -0.13 34 34
mol:glutathione 0 0 -10000 0 -10000 0 0
PAWR 0.04 0.006 -10000 0 0 11 11
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD 0.001 0.084 -10000 0 -0.25 30 30
TNFR1A/BAG4/TNF-alpha 0.06 0.045 -10000 0 -0.11 15 15
mol:Sphingosine-1-phosphate -0.018 0.007 0 74 -10000 0 74
MAP2K1 -0.008 0.041 0.17 15 -0.19 7 22
mol:C11AG 0 0 -10000 0 -10000 0 0
RELA 0.04 0.006 -10000 0 0 10 10
CYCS 0.003 0.047 -10000 0 -0.18 14 14
TNFRSF1A 0.036 0.014 -10000 0 0 72 72
NFKB1 0.036 0.013 -10000 0 0 66 66
TNFR1A/BAG4 0.045 0.037 -10000 0 -0.13 14 14
EIF2AK2 -0.003 0.055 0.18 23 -0.19 10 33
TNF-alpha/TNFR1A/FAN 0.059 0.052 -10000 0 -0.14 21 21
response to hydrogen peroxide 0 0 -10000 0 -10000 0 0
CASP8 -0.005 0.14 -10000 0 -0.4 48 48
MAP2K2 -0.005 0.04 0.18 14 -0.19 6 20
SMPD3 -0.004 0.1 0.19 4 -0.29 47 51
TNF 0.04 0.008 -10000 0 0 22 22
PKC zeta/PAR4 0.057 0.017 -10000 0 -0.13 1 1
mol:PHOSPHOCHOLINE 0.004 0.031 0.15 2 -0.14 7 9
NF kappa B1/RelA/I kappa B alpha 0.079 0.081 -10000 0 -0.12 59 59
AIFM1 0.004 0.042 0.12 1 -0.17 14 15
BCL2 0.036 0.014 -10000 0 0 67 67
ceramide signaling pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
MAP4K4 -0.025 0.13 0.27 1 -0.38 42 43
BAG4 0.037 0.012 -10000 0 0 55 55
BAD -0.009 0.047 0.19 4 -0.13 30 34
NFKBIA 0.036 0.013 -10000 0 0 64 64
BIRC3 0.025 0.02 -10000 0 0 210 210
BAX -0.008 0.045 0.17 3 -0.13 28 31
EnzymeConsortium:3.1.4.12 -0.003 0.031 0.064 2 -0.084 38 40
IKBKB -0.025 0.13 0.22 12 -0.37 40 52
MAP2K2 -0.007 0.043 0.16 10 -0.14 8 18
MAP2K1 -0.011 0.045 0.16 10 -0.14 9 19
SMPD1 -0.003 0.036 -10000 0 -0.1 32 32
GO:0005551 0 0 -10000 0 -10000 0 0
FADD/Caspase 8 -0.016 0.14 0.25 9 -0.37 43 52
MAP2K4 -0.009 0.04 -10000 0 -0.14 21 21
protein ubiquitination -0.031 0.13 0.26 1 -0.37 42 43
EnzymeConsortium:2.7.1.37 -0.011 0.046 0.16 9 -0.16 5 14
response to UV 0 0 0.002 9 -0.002 3 12
RAF1 -0.009 0.047 0.17 10 -0.14 15 25
CRADD 0.04 0.006 -10000 0 0 10 10
mol:ceramide -0.004 0.046 0.12 1 -0.13 37 38
I-kappa-B-alpha/RELA/p50/ubiquitin 0.041 0.042 -10000 0 -0.11 35 35
MADD 0.041 0.005 -10000 0 0 9 9
MAP3K1 -0.009 0.043 0.12 1 -0.13 33 34
TRADD 0.037 0.013 -10000 0 0 61 61
RELA/p50 0.04 0.006 -10000 0 0 10 10
MAPK3 -0.007 0.046 0.16 9 -0.17 6 15
MAPK1 -0.01 0.052 0.16 8 -0.18 15 23
p50/RELA/I-kappa-B-alpha 0.044 0.05 -10000 0 -0.14 35 35
FADD -0.021 0.14 0.24 9 -0.37 42 51
KSR1 -0.006 0.044 0.16 5 -0.13 24 29
MAPK8 -0.015 0.044 0.18 3 -0.15 12 15
TRAF2 0.039 0.01 -10000 0 0 32 32
response to radiation 0 0 -10000 0 -10000 0 0
CHUK -0.034 0.13 0.26 1 -0.35 46 47
TNF R/SODD 0.045 0.037 -10000 0 -0.13 14 14
TNF 0.04 0.008 -10000 0 0 22 22
CYCS -0.01 0.048 0.15 3 -0.14 25 28
IKBKG -0.032 0.13 0.26 1 -0.37 39 40
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD -0.02 0.14 -10000 0 -0.39 42 42
RELA 0.04 0.006 -10000 0 0 10 10
RIPK1 0.039 0.01 -10000 0 0 32 32
AIFM1 -0.009 0.046 0.13 6 -0.14 23 29
TNF/TNF R/SODD 0.06 0.045 -10000 0 -0.11 15 15
TNFRSF1A 0.036 0.014 -10000 0 0 72 72
response to heat 0 0 -10000 0 -10000 0 0
CASP8 0.017 0.13 -10000 0 -0.65 18 18
NSMAF -0.017 0.14 0.24 15 -0.38 41 56
response to hydrogen peroxide 0 0 0.002 9 -0.002 3 12
BCL2 0.036 0.014 -10000 0 0 67 67
Syndecan-3-mediated signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
CTTN 0.039 0.009 -9999 0 0 30 30
Syndecan-3/Src/Cortactin 0.022 0.091 -9999 0 -0.35 13 13
Syndecan-3/Neurocan 0.001 0.064 -9999 0 -0.41 12 12
POMC 0.04 0.006 -9999 0 0 12 12
EGFR 0.036 0.014 -9999 0 0 67 67
Syndecan-3/EGFR 0.032 0.075 -9999 0 -0.42 12 12
AGRP 0.037 0.012 -9999 0 0 55 55
NCSTN 0.04 0.008 -9999 0 0 22 22
PSENEN 0.034 0.016 -9999 0 0 96 96
RP11-540L11.1 0 0 -9999 0 -10000 0 0
APH1B 0.035 0.014 -9999 0 0 79 79
APH1A 0.038 0.011 -9999 0 0 42 42
NCAN 0 0 -9999 0 -10000 0 0
long-term memory 0.042 0.081 -9999 0 -0.39 12 12
Syndecan-3/IL8 0.026 0.073 -9999 0 -0.41 12 12
PSEN1 0.039 0.01 -9999 0 0 31 31
Src/Cortactin 0.052 0.032 -9999 0 -0.13 11 11
FYN 0.034 0.016 -9999 0 0 94 94
limb bud formation 0.002 0.065 -9999 0 -0.44 11 11
MC4R 0 0 -9999 0 -10000 0 0
SRC 0.039 0.009 -9999 0 0 28 28
PTN 0.023 0.02 -9999 0 0 241 241
FGFR/FGF/Syndecan-3 0.002 0.065 -9999 0 -0.44 11 11
neuron projection morphogenesis -0.011 0.068 -9999 0 -0.38 10 10
Syndecan-3/AgRP 0.034 0.073 -9999 0 -0.41 12 12
Syndecan-3/AgRP/MC4R 0.032 0.071 -9999 0 -0.4 12 12
Fyn/Cortactin 0.037 0.055 -9999 0 -0.13 44 44
SDC3 0.003 0.064 -9999 0 -0.46 10 10
GO:0007205 0 0 -9999 0 -10000 0 0
positive regulation of leukocyte migration 0.026 0.072 -9999 0 -0.41 12 12
IL8 0.031 0.018 -9999 0 0 129 129
Syndecan-3/Fyn/Cortactin 0.043 0.083 -9999 0 -0.4 12 12
Syndecan-3/CASK 0.001 0.064 -9999 0 -0.41 12 12
alpha-MSH/MC4R 0.03 0.004 -9999 0 -10000 0 0
Gamma Secretase 0.067 0.085 -9999 0 -0.12 63 63
S1P4 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 Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
mol:S1P 0 0 -10000 0 -10000 0 0
GNAO1 0.035 0.015 -10000 0 0 85 85
CDC42/GTP 0.009 0.084 -10000 0 -0.17 70 70
PLCG1 -0.014 0.072 -10000 0 -0.18 68 68
mol:GTP 0 0 -10000 0 -10000 0 0
GNAI2 0.04 0.006 -10000 0 0 13 13
GNAI3 0.038 0.011 -10000 0 0 45 45
G12/G13 0.053 0.028 -10000 0 -0.13 8 8
cell migration 0.008 0.083 -10000 0 -0.17 70 70
S1PR5 0 0 -10000 0 -10000 0 0
S1PR4 0 0 -10000 0 -10000 0 0
MAPK3 -0.013 0.073 -10000 0 -0.18 66 66
MAPK1 -0.008 0.065 -10000 0 -0.17 58 58
S1P/S1P5/Gi -0.008 0.078 -10000 0 -0.18 69 69
GNAI1 0.034 0.015 -10000 0 0 93 93
CDC42/GDP 0.029 0.012 -10000 0 -0.12 3 3
S1P/S1P5/G12 0.026 0.007 -10000 0 -10000 0 0
RHOA -0.014 0.03 0.19 9 -0.17 1 10
S1P/S1P4/Gi -0.008 0.078 -10000 0 -0.18 69 69
mol:GDP 0 0 -10000 0 -10000 0 0
GNAZ 0.038 0.011 -10000 0 0 46 46
S1P/S1P4/G12/G13 0.046 0.023 -10000 0 -0.097 8 8
GNA12 0.039 0.01 -10000 0 0 33 33
GNA13 0.039 0.008 -10000 0 0 23 23
CDC42 0.04 0.007 -10000 0 0 18 18
Arf6 downstream pathway

Figure S92.  Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S92.  Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PLAUR -0.033 0.2 -10000 0 -0.8 34 34
regulation of axonogenesis -0.002 0.048 0.24 11 -10000 0 11
myoblast fusion -0.013 0.1 0.35 36 -10000 0 36
mol:GTP 0.016 0.066 -10000 0 -0.2 43 43
regulation of calcium-dependent cell-cell adhesion -0.036 0.089 0.2 40 -10000 0 40
ARF1/GTP 0.037 0.059 -10000 0 -0.16 38 38
mol:GM1 0.003 0.046 -10000 0 -0.15 40 40
mol:Choline -0.001 0.034 -10000 0 -0.14 26 26
lamellipodium assembly -0.009 0.12 -10000 0 -0.4 44 44
MAPK3 0.009 0.083 -10000 0 -0.28 40 40
ARF6/GTP/NME1/Tiam1 0.037 0.089 -10000 0 -0.2 40 40
ARF1 0.038 0.011 -10000 0 0 45 45
ARF6/GDP 0.013 0.1 -10000 0 -0.36 36 36
ARF1/GDP 0.018 0.1 -10000 0 -0.32 40 40
ARF6 0.042 0.045 -10000 0 -0.13 33 33
RAB11A 0.04 0.008 -10000 0 0 19 19
TIAM1 0.032 0.023 -10000 0 -0.045 28 28
fibronectin binding 0 0 -10000 0 -10000 0 0
MAPK1 0.011 0.079 -10000 0 -0.28 35 35
actin filament bundle formation -0.025 0.11 0.32 44 -10000 0 44
KALRN 0.003 0.074 -10000 0 -0.26 35 35
RAB11FIP3/RAB11A 0.054 0.026 -10000 0 -0.13 6 6
RhoA/GDP 0.026 0.11 -10000 0 -0.32 44 44
NME1 0.031 0.024 -10000 0 -0.047 33 33
Rac1/GDP 0.025 0.11 -10000 0 -0.32 44 44
substrate adhesion-dependent cell spreading 0.016 0.066 -10000 0 -0.2 43 43
cortical actin cytoskeleton organization -0.009 0.12 -10000 0 -0.41 43 43
RAC1 0.039 0.009 -10000 0 0 28 28
liver development 0.016 0.066 -10000 0 -0.2 43 43
ARF6/GTP 0.016 0.066 -10000 0 -0.2 43 43
RhoA/GTP 0.04 0.062 -10000 0 -0.16 43 43
mol:GDP -0.003 0.097 -10000 0 -0.34 37 37
ARF6/GTP/RAB11FIP3/RAB11A 0.057 0.065 -10000 0 -0.14 43 43
RHOA 0.04 0.006 -10000 0 0 13 13
PLD1 0.008 0.047 -10000 0 -0.17 31 31
RAB11FIP3 0.038 0.01 -10000 0 0 37 37
tube morphogenesis -0.009 0.12 -10000 0 -0.4 44 44
ruffle organization 0.002 0.048 -10000 0 -0.24 11 11
regulation of epithelial cell migration 0.016 0.066 -10000 0 -0.2 43 43
PLD2 0.015 0.047 -10000 0 -0.15 36 36
PIP5K1A 0.002 0.048 -10000 0 -0.25 11 11
mol:Phosphatidic acid -0.001 0.034 -10000 0 -0.14 26 26
Rac1/GTP -0.009 0.12 -10000 0 -0.41 43 43
Signaling mediated by p38-gamma and p38-delta

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
EEF2K -0.019 0.015 0.059 14 -10000 0 14
SNTA1 0.039 0.01 -10000 0 0 34 34
response to hypoxia 0 0 -10000 0 -10000 0 0
STMN1 -0.018 0.016 0.059 15 -10000 0 15
MAPK12 -0.008 0.038 0.21 4 -0.16 12 16
CCND1 -0.04 0.13 -10000 0 -0.37 70 70
p38 gamma/SNTA1 0.023 0.068 0.22 8 -0.17 28 36
MAP2K3 0.038 0.011 -10000 0 0 43 43
PKN1 0.034 0.016 -10000 0 0 96 96
G2/M transition checkpoint -0.008 0.038 0.21 4 -0.16 12 16
MAP2K6 0.002 0.04 0.24 2 -0.17 19 21
MAPT 0 0.047 0.14 8 -0.19 13 21
MAPK13 -0.017 0.007 0 84 -10000 0 84
hyperosmotic response 0 0 -10000 0 -10000 0 0
ZAK 0.004 0.048 -10000 0 -0.2 29 29
Regulation of nuclear SMAD2/3 signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
EP300 0.036 0.016 0.078 1 -0.056 3 4
HSPA8 0.039 0.01 -10000 0 0 34 34
SMAD3/SMAD4/ER alpha 0.063 0.091 0.23 34 -0.16 18 52
AKT1 0.04 0.017 -10000 0 -0.098 5 5
GSC 0.026 0.1 -10000 0 -0.73 5 5
NKX2-5 0.038 0.018 0.082 2 -0.055 14 16
muscle cell differentiation -0.045 0.093 0.28 11 -10000 0 11
SMAD2-3/SMAD4/SP1 0.072 0.12 -10000 0 -0.2 9 9
SMAD4 0.036 0.047 -10000 0 -0.1 11 11
CBFB 0.036 0.014 -10000 0 0 67 67
SAP18 0.039 0.008 -10000 0 0 24 24
Cbp/p300/MSG1 0.059 0.055 -10000 0 -0.14 22 22
SMAD3/SMAD4/VDR 0.077 0.099 -10000 0 -0.21 12 12
MYC 0.022 0.021 0.11 5 -0.042 2 7
CDKN2B -0.037 0.16 -10000 0 -1.3 5 5
AP1 0.005 0.092 -10000 0 -0.22 41 41
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1 0.006 0.12 0.19 3 -0.32 42 45
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1 0.014 0.059 -10000 0 -0.21 26 26
SP3 0.036 0.023 0.081 1 -0.053 32 33
CREB1 0.04 0.007 -10000 0 0 17 17
FOXH1 0.028 0.025 -10000 0 -0.059 15 15
SMAD3/SMAD4/GR 0.053 0.078 -10000 0 -0.15 19 19
GATA3 0.042 0.012 -10000 0 -10000 0 0
SKI/SIN3/HDAC complex/NCoR1 0.003 0.094 -10000 0 -0.27 34 34
MEF2C/TIF2 0.062 0.1 0.22 101 -0.21 16 117
endothelial cell migration -0.03 0.11 0.94 5 -10000 0 5
MAX 0.029 0.027 0.097 3 -0.035 77 80
RBBP7 0.039 0.009 -10000 0 0 25 25
RBBP4 0.038 0.011 -10000 0 0 40 40
RUNX2 0.038 0.011 -10000 0 0 40 40
RUNX3 0.039 0.01 -10000 0 0 33 33
RUNX1 0.039 0.01 -10000 0 0 33 33
CTBP1 0.038 0.012 -10000 0 0 49 49
NR3C1 0.026 0.027 0.097 3 -0.035 77 80
VDR 0.038 0.011 -10000 0 0 43 43
CDKN1A 0.013 0.075 -10000 0 -0.65 2 2
KAT2B 0 0.002 -10000 0 -10000 0 0
SMAD2/SMAD2/SMAD4/FOXH1 0.056 0.062 -10000 0 -0.22 3 3
DCP1A 0.04 0.007 -10000 0 0 17 17
SKI 0.039 0.009 -10000 0 0 29 29
SERPINE1 0.028 0.11 -10000 0 -0.95 5 5
SMAD3/SMAD4/ATF2 0.062 0.074 -10000 0 -0.15 13 13
SMAD3/SMAD4/ATF3 0.058 0.068 -10000 0 -0.14 7 7
SAP30 0.038 0.011 -10000 0 0 46 46
Cbp/p300/PIAS3 0.057 0.058 0.17 1 -0.14 27 28
JUN 0.001 0.087 0.18 9 -0.22 38 47
SMAD3/SMAD4/IRF7 0.07 0.07 -10000 0 -0.15 7 7
TFE3 0.038 0.033 0.11 1 -0.082 34 35
COL1A2 -0.093 0.25 -10000 0 -0.61 103 103
mesenchymal cell differentiation -0.062 0.069 0.14 9 -10000 0 9
DLX1 0.04 0.008 -10000 0 0 19 19
TCF3 0.036 0.014 -10000 0 0 74 74
FOS 0.025 0.029 -10000 0 -0.05 28 28
SMAD3/SMAD4/Max 0.062 0.068 -10000 0 -0.14 6 6
Cbp/p300/SNIP1 0.058 0.055 -10000 0 -0.14 24 24
ZBTB17 0.038 0.01 0.1 3 -0.04 4 7
LAMC1 0.01 0.075 -10000 0 -0.26 26 26
TGIF2/HDAC complex/SMAD3/SMAD4 0.059 0.075 -10000 0 -0.16 13 13
IRF7 0.04 0.012 0.087 1 -10000 0 1
ESR1 0.046 0.037 0.12 90 0 91 181
HNF4A 0.038 0.01 -10000 0 0 38 38
MEF2C 0.049 0.11 0.2 145 -0.23 14 159
SMAD2-3/SMAD4 0.07 0.073 -10000 0 -0.14 6 6
Cbp/p300/Src-1 0.058 0.06 -10000 0 -0.14 31 31
IGHV3OR16-13 0.01 0.057 -10000 0 -0.45 8 8
TGIF2/HDAC complex 0.037 0.012 -10000 0 0 50 50
CREBBP 0.037 0.014 -10000 0 -0.045 2 2
SKIL 0.025 0.02 -10000 0 0 215 215
HDAC1 0.037 0.012 -10000 0 0 49 49
HDAC2 0.038 0.01 -10000 0 0 38 38
SNIP1 0.039 0.009 -10000 0 0 28 28
GCN5L2 0.039 0.012 -10000 0 -0.045 3 3
SMAD3/SMAD4/TFE3 0.076 0.083 -10000 0 -0.16 21 21
MSG1/HSC70 0.052 0.026 -10000 0 -0.13 5 5
SMAD2 0.039 0.024 -10000 0 -0.065 20 20
SMAD3 0.034 0.047 -10000 0 -0.1 13 13
SMAD3/E2F4-5/DP1/p107/SMAD4 0.019 0.065 0.16 1 -0.2 19 20
SMAD2/SMAD2/SMAD4 -0.003 0.056 0.16 9 -0.17 32 41
NCOR1 0.037 0.013 -10000 0 0 58 58
NCOA2 0.037 0.013 -10000 0 0 60 60
NCOA1 0.04 0.008 -10000 0 0 22 22
MYOD/E2A 0.051 0.024 -10000 0 -0.13 1 1
SMAD2-3/SMAD4/SP1/MIZ-1 0.084 0.12 -10000 0 -0.2 9 9
IFNB1 0.013 0.049 0.17 1 -0.16 2 3
SMAD3/SMAD4/MEF2C 0.088 0.11 0.27 47 -0.22 13 60
CITED1 0.039 0.01 -10000 0 0 35 35
SMAD2-3/SMAD4/ARC105 0.068 0.066 -10000 0 -0.13 4 4
RBL1 0.037 0.012 -10000 0 0 54 54
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB 0.025 0.072 -10000 0 -0.41 7 7
RUNX1-3/PEBPB2 0.065 0.041 -10000 0 -0.11 13 13
SMAD7 -0.001 0.14 -10000 0 -0.36 29 29
MYC/MIZ-1 0.019 0.058 0.2 3 -0.14 49 52
SMAD3/SMAD4 -0.002 0.1 0.26 2 -0.34 22 24
IL10 0.022 0.061 0.23 15 -10000 0 15
PIASy/HDAC complex 0.036 0.014 -10000 0 -0.038 4 4
PIAS3 0.038 0.013 -10000 0 -0.002 50 50
CDK2 0.037 0.014 -10000 0 -0.042 3 3
IL5 0.023 0.061 0.23 13 -10000 0 13
CDK4 0.038 0.013 -10000 0 -0.045 3 3
PIAS4 0.036 0.014 -10000 0 -0.038 4 4
ATF3 0.036 0.013 -10000 0 0 63 63
SMAD3/SMAD4/SP1 0.054 0.11 -10000 0 -0.18 21 21
FOXG1 -0.001 0.001 -10000 0 -10000 0 0
FOXO3 0.01 0.012 -10000 0 -0.11 5 5
FOXO1 0.01 0.012 -10000 0 -0.11 5 5
FOXO4 0.01 0.012 -10000 0 -0.11 5 5
heart looping 0.049 0.1 0.2 145 -0.22 14 159
CEBPB 0.036 0.017 -10000 0 -0.061 5 5
SMAD3/SMAD4/DLX1 0.067 0.067 -10000 0 -0.14 6 6
MYOD1 0.04 0.007 -10000 0 0 16 16
SMAD3/SMAD4/HNF4 0.064 0.068 -10000 0 -0.14 6 6
SMAD3/SMAD4/GATA3 0.077 0.07 -10000 0 -0.16 1 1
SnoN/SIN3/HDAC complex/NCoR1 0.025 0.02 -10000 0 0 215 215
SMAD3/SMAD4/RUNX1-3/PEBPB2 0.088 0.082 -10000 0 -0.14 1 1
SMAD3/SMAD4/SP1-3 0.07 0.12 -10000 0 -0.21 21 21
MED15 0 0 -10000 0 -10000 0 0
SP1 0.018 0.066 -10000 0 -0.099 122 122
SIN3B 0.036 0.014 -10000 0 0 67 67
SIN3A 0.039 0.009 -10000 0 0 30 30
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5 0.071 0.077 -10000 0 -0.17 11 11
ITGB5 -0.004 0.091 0.21 13 -0.27 29 42
TGIF/SIN3/HDAC complex/CtBP 0.008 0.087 -10000 0 -0.26 30 30
SMAD3/SMAD4/AR 0.04 0.088 -10000 0 -0.16 30 30
AR 0.032 0.017 -10000 0 0 118 118
negative regulation of cell growth 0.019 0.076 0.19 1 -0.25 21 22
SMAD3/SMAD4/MYOD 0.068 0.067 -10000 0 -0.14 6 6
E2F5 0.036 0.013 -10000 0 0 64 64
E2F4 0.036 0.013 -10000 0 0 64 64
SMAD2/SMAD2/SMAD4/FOXH1/SMIF 0.069 0.079 -10000 0 -0.15 5 5
SMAD2-3/SMAD4/FOXO1-3a-4 0.026 0.051 -10000 0 -0.29 7 7
TFDP1 0.037 0.012 -10000 0 0 55 55
SMAD3/SMAD4/AP1 0.031 0.11 0.26 3 -0.23 37 40
SMAD3/SMAD4/RUNX2 0.063 0.07 -10000 0 -0.14 9 9
TGIF2 0.037 0.012 -10000 0 0 50 50
TGIF1 0 0 -10000 0 -10000 0 0
ATF2 0.039 0.009 -10000 0 0 30 30
Ephrin A reverse signaling

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
MAPKKK cascade 0.037 0.042 -10000 0 -0.11 33 33
EFNA5 0.034 0.015 -10000 0 0 93 93
FYN -0.015 0.033 0.18 4 -10000 0 4
neuron projection morphogenesis 0.037 0.042 -10000 0 -0.11 33 33
cell-cell signaling 0 0 -10000 0 -10000 0 0
Ephrin A5/EPHA5 0.038 0.042 -10000 0 -0.11 33 33
EPHA5 0.039 0.008 -10000 0 0 24 24
Hedgehog signaling events mediated by Gli proteins

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
HDAC1 0.037 0.012 -10000 0 0 49 49
HDAC2 0.038 0.01 -10000 0 0 38 38
GNB1/GNG2 0.068 0.042 -10000 0 -0.12 16 16
forebrain development 0.011 0.11 -10000 0 -0.38 29 29
GNAO1 0.035 0.015 -10000 0 0 85 85
SMO/beta Arrestin2 0.054 0.025 -10000 0 -0.13 4 4
SMO 0.04 0.009 -10000 0 -0.001 24 24
ARRB2 0.038 0.012 -10000 0 0 46 46
GLI3/SPOP 0.025 0.12 0.23 1 -0.34 29 30
mol:GTP 0 0.001 -10000 0 -10000 0 0
GSK3B 0.039 0.008 -10000 0 0 23 23
GNAI2 0.04 0.006 -10000 0 0 13 13
SIN3/HDAC complex 0.076 0.053 -10000 0 -0.11 12 12
GNAI1 0.034 0.016 -10000 0 0 93 93
XPO1 0.039 0.012 -10000 0 -0.003 38 38
GLI1/Su(fu) 0.017 0.11 -10000 0 -0.4 24 24
SAP30 0.038 0.011 -10000 0 0 46 46
mol:GDP 0.04 0.009 -10000 0 -0.001 24 24
MIM/GLI2A 0.032 0.025 -10000 0 -0.12 2 2
IFT88 0.037 0.013 -10000 0 0 61 61
GNAI3 0.038 0.011 -10000 0 0 45 45
GLI2 0.015 0.077 0.18 5 -0.26 17 22
GLI3 0.007 0.12 0.21 3 -0.35 29 32
CSNK1D 0.039 0.008 -10000 0 0 24 24
CSNK1E 0.037 0.012 -10000 0 0 53 53
SAP18 0.039 0.008 -10000 0 0 24 24
embryonic digit morphogenesis 0.037 0.013 -10000 0 0 61 61
GNG2 0.039 0.009 -10000 0 0 29 29
Gi family/GTP 0.002 0.077 -10000 0 -0.25 28 28
SIN3B 0.036 0.014 -10000 0 0 67 67
SIN3A 0.039 0.009 -10000 0 0 30 30
GLI3/Su(fu) 0.019 0.12 0.21 3 -0.33 32 35
GLI2/Su(fu) 0.022 0.086 0.18 2 -0.26 23 25
FOXA2 0.022 0.1 -10000 0 -0.57 13 13
neural tube patterning 0.011 0.11 -10000 0 -0.38 29 29
SPOP 0.04 0.008 -10000 0 0 21 21
Su(fu)/PIAS1 0.041 0.055 -10000 0 -0.19 20 20
GNB1 0.039 0.01 -10000 0 0 33 33
CSNK1G2 0.036 0.013 -10000 0 0 64 64
CSNK1G3 0.039 0.01 -10000 0 0 31 31
MTSS1 0.032 0.025 -10000 0 -0.12 2 2
embryonic limb morphogenesis 0.011 0.11 -10000 0 -0.38 29 29
SUFU 0.022 0.039 -10000 0 -0.24 10 10
LGALS3 0.036 0.014 -10000 0 0 67 67
catabolic process 0.027 0.13 -10000 0 -0.36 31 31
GLI3A/CBP 0.046 0.015 -10000 0 -10000 0 0
KIF3A 0.038 0.011 -10000 0 0 46 46
GLI1 0.01 0.11 -10000 0 -0.38 29 29
RAB23 0.04 0.006 -10000 0 0 13 13
CSNK1A1 0.039 0.008 -10000 0 0 23 23
IFT172 0.039 0.009 -10000 0 0 28 28
RBBP7 0.039 0.009 -10000 0 0 25 25
Su(fu)/Galectin3 0.037 0.053 -10000 0 -0.18 19 19
GNAZ 0.038 0.012 -10000 0 0 46 46
RBBP4 0.038 0.011 -10000 0 0 40 40
CSNK1G1 0.04 0.007 -10000 0 0 16 16
PIAS1 0.039 0.008 -10000 0 0 24 24
PRKACA 0.035 0.015 -10000 0 0 84 84
GLI2/SPOP 0.032 0.086 -10000 0 -0.27 20 20
STK36 0.039 0.011 -10000 0 -0.003 33 33
Gi family/GNB1/GNG2/GDP -0.002 0.087 -10000 0 -0.24 38 38
PTCH1 0.011 0.1 -10000 0 -0.35 29 29
MIM/GLI1 0.024 0.1 -10000 0 -0.35 21 21
CREBBP 0.046 0.015 -10000 0 -10000 0 0
Su(fu)/SIN3/HDAC complex 0.004 0.11 0.17 4 -0.32 34 38
Class I PI3K signaling events mediated by Akt

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BCL2L1 -0.016 0.009 -10000 0 -10000 0 0
BAD/BCL-XL/YWHAZ 0.062 0.06 0.18 72 -0.11 16 88
CDKN1B 0.013 0.091 0.21 31 -0.33 24 55
CDKN1A 0.004 0.084 0.2 9 -0.32 28 37
FRAP1 0.039 0.009 -10000 0 0 28 28
PRKDC 0.038 0.011 -10000 0 0 44 44
FOXO3 0.005 0.081 -10000 0 -0.31 30 30
AKT1 0.006 0.081 -10000 0 -0.34 26 26
BAD 0.041 0.005 -10000 0 0 7 7
AKT3 0.004 0.046 -10000 0 -0.2 26 26
mol:GTP 0 0 -10000 0 -10000 0 0
FOXO4 0.005 0.081 -10000 0 -0.31 30 30
AKT1/ASK1 0.026 0.09 -10000 0 -0.31 31 31
BAD/YWHAZ 0.056 0.042 -10000 0 -0.11 6 6
RICTOR 0.037 0.013 -10000 0 0 59 59
RAF1 0.04 0.008 -10000 0 0 22 22
JNK cascade -0.025 0.087 0.3 31 -10000 0 31
TSC1 0.002 0.078 0.26 1 -0.32 25 26
YWHAZ 0.034 0.016 -10000 0 0 96 96
AKT1/RAF1 0.032 0.093 0.24 1 -0.32 29 30
EP300 0.036 0.014 -10000 0 0 69 69
mol:GDP 0.004 0.083 -10000 0 -0.32 30 30
mol:PI-3-4-5-P3 0 0 -10000 0 -10000 0 0
TSC2 0 0.082 0.26 1 -0.32 30 31
YWHAQ 0.04 0.007 -10000 0 0 18 18
TBC1D4 0.004 0.03 0.24 4 -0.17 7 11
MAP3K5 0.037 0.013 -10000 0 0 60 60
MAPKAP1 0.04 0.008 -10000 0 0 21 21
negative regulation of cell cycle -0.022 0.087 0.3 17 -0.22 2 19
YWHAH 0.038 0.011 -10000 0 0 46 46
AKT1S1 0.002 0.077 0.27 1 -0.33 24 25
CASP9 0 0.079 -10000 0 -0.32 27 27
YWHAB 0.038 0.011 -10000 0 0 45 45
p27Kip1/KPNA1 0.033 0.11 0.29 6 -0.32 28 34
GBL 0.039 0.009 -10000 0 0 26 26
PDK1/Src/Hsp90 0.049 0.023 -10000 0 -0.11 6 6
YWHAE 0.037 0.013 -10000 0 0 58 58
SRC 0.039 0.009 -10000 0 0 28 28
AKT2/p21CIP1 0.007 0.077 0.2 8 -0.29 26 34
KIAA1303 0 0 -10000 0 -10000 0 0
mTOR/RHEB/GTP/Raptor/GBL 0.018 0.097 -10000 0 -0.36 27 27
CHUK -0.002 0.084 -10000 0 -0.32 30 30
BAD/BCL-XL 0.025 0.086 0.23 1 -0.31 26 27
mTORC2 0.077 0.061 -10000 0 -0.11 32 32
AKT2 0.014 0.025 -10000 0 -0.2 7 7
FOXO1-3a-4/14-3-3 family 0.024 0.11 0.24 3 -0.35 20 23
PDPK1 0.039 0.009 -10000 0 0 29 29
MDM2 0.005 0.088 0.2 15 -0.32 28 43
MAPKKK cascade -0.032 0.092 0.32 29 -0.24 1 30
MDM2/Cbp/p300 0.04 0.1 0.33 3 -0.32 28 31
TSC1/TSC2 -0.003 0.083 0.28 5 -0.31 30 35
proteasomal ubiquitin-dependent protein catabolic process 0.038 0.1 0.32 3 -0.31 28 31
glucose import -0.004 0.036 0.21 11 -0.16 7 18
mTOR/RHEB/GDP/Raptor/GBL/PRAS40 0.014 0.089 0.25 1 -0.34 11 12
response to stress 0 0 -10000 0 -10000 0 0
SLC2A4 -0.005 0.033 0.21 8 -0.16 7 15
GSK3A 0.005 0.084 0.22 11 -0.32 26 37
FOXO1 0.005 0.081 -10000 0 -0.31 30 30
GSK3B 0.004 0.087 0.22 13 -0.32 28 41
SFN 0.035 0.015 -10000 0 0 83 83
G1/S transition of mitotic cell cycle 0.008 0.097 0.28 11 -0.32 27 38
p27Kip1/14-3-3 family 0.02 0.08 0.22 1 -0.35 11 12
PRKACA 0.035 0.015 -10000 0 0 84 84
KPNA1 0.039 0.009 -10000 0 0 28 28
HSP90AA1 0 0 -10000 0 -10000 0 0
YWHAG 0.039 0.009 -10000 0 0 25 25
RHEB 0.037 0.012 -10000 0 0 53 53
CREBBP 0.037 0.012 -10000 0 0 53 53
Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1 0.037 0.013 -10000 0 0 58 58
NFATC1 0.014 0.1 0.26 5 -0.34 16 21
NFATC2 0.023 0.061 0.16 12 -0.19 15 27
NFATC3 0.025 0.016 -10000 0 -10000 0 0
YWHAE 0.037 0.013 -10000 0 0 58 58
Calcineurin A alpha-beta B1/CABIN1 -0.007 0.087 0.17 2 -0.25 32 34
Exportin 1/Ran/NUP214 0.064 0.051 -10000 0 -0.11 32 32
mol:DAG 0.001 0.002 -10000 0 -10000 0 0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV 0.026 0.1 -10000 0 -0.26 23 23
BCL2/BAX 0.051 0.023 -10000 0 -0.13 1 1
CaM/Ca2+/Calcineurin A alpha-beta B1 0.029 0.019 -10000 0 -0.12 5 5
CaM/Ca2+ 0.029 0.019 -10000 0 -0.12 5 5
BAX 0.039 0.008 -10000 0 0 23 23
MAPK14 0.04 0.008 -10000 0 0 20 20
BAD 0.041 0.005 -10000 0 0 7 7
CABIN1/MEF2D 0.011 0.093 -10000 0 -0.25 29 29
Calcineurin A alpha-beta B1/BCL2 0.036 0.014 -10000 0 0 67 67
FKBP8 0.036 0.014 -10000 0 0 71 71
activation-induced cell death of T cells -0.011 0.092 0.25 29 -10000 0 29
KPNB1 0.039 0.009 -10000 0 0 25 25
KPNA2 0.035 0.014 -10000 0 0 79 79
XPO1 0.039 0.01 -10000 0 0 35 35
SFN 0.035 0.015 -10000 0 0 83 83
MAP3K8 0.04 0.009 -10000 0 0 24 24
NFAT4/CK1 alpha 0.027 0.044 0.18 1 -0.15 10 11
MEF2D/NFAT1/Cbp/p300 0.067 0.093 0.24 3 -0.2 14 17
CABIN1 -0.006 0.087 0.17 2 -0.25 32 34
CALM1 0.04 0.009 -10000 0 0 26 26
RAN 0.04 0.008 -10000 0 0 21 21
MAP3K1 0.036 0.013 -10000 0 0 63 63
CAMK4 0.037 0.012 -10000 0 0 55 55
mol:Ca2+ 0.001 0.004 -10000 0 -10000 0 0
MAPK3 0.04 0.007 -10000 0 0 18 18
YWHAH 0.038 0.011 -10000 0 0 46 46
Calcineurin A alpha-beta B1/AKAP79/PKA 0.05 0.026 -10000 0 -0.13 2 2
YWHAB 0.038 0.011 -10000 0 0 45 45
MAPK8 0.04 0.01 -10000 0 0 29 29
MAPK9 0.038 0.011 -10000 0 0 39 39
YWHAG 0.039 0.009 -10000 0 0 25 25
FKBP1A 0.038 0.011 -10000 0 0 44 44
NFAT1-c-4/YWHAQ 0.028 0.11 0.26 4 -0.29 25 29
PRKCH 0.038 0.01 -10000 0 0 36 36
CABIN1/Cbp/p300 0.043 0.051 -10000 0 -0.16 24 24
CASP3 0.037 0.013 -10000 0 0 62 62
PIM1 0.038 0.01 -10000 0 0 36 36
Calcineurin A alpha-beta B1/FKBP12/FK506 0.026 0.011 -10000 0 -0.1 2 2
apoptosis 0.017 0.035 -10000 0 -0.19 10 10
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1 0.023 0.075 -10000 0 -0.28 15 15
PRKCB 0 0 -10000 0 -10000 0 0
PRKCE 0.039 0.009 -10000 0 0 28 28
JNK2/NFAT4 0.027 0.066 -10000 0 -0.15 61 61
BAD/BCL-XL 0.051 0.031 -10000 0 -0.13 10 10
PRKCD 0.037 0.012 -10000 0 0 51 51
NUP214 0.038 0.011 -10000 0 0 43 43
PRKCZ 0.04 0.009 -10000 0 0 27 27
PRKCA 0.035 0.015 -10000 0 0 86 86
PRKCG 0.039 0.009 -10000 0 0 27 27
PRKCQ 0.035 0.015 -10000 0 0 85 85
FKBP38/BCL2 0.046 0.028 -10000 0 -0.13 2 2
EP300 0.037 0.014 -10000 0 0 69 69
PRKCB1 0.038 0.011 -10000 0 0 46 46
CSNK2A1 0.038 0.012 -10000 0 0 47 47
NFATc/JNK1 0.028 0.11 0.26 4 -0.32 17 21
CaM/Ca2+/FKBP38 0.047 0.027 -10000 0 -0.13 4 4
FKBP12/FK506 0.028 0.012 -10000 0 -0.12 2 2
CSNK1A1 0.017 0.018 0.097 5 -0.11 4 9
CaM/Ca2+/CAMK IV 0.048 0.027 -10000 0 -0.11 7 7
NFATc/ERK1 0.029 0.11 0.28 5 -0.32 16 21
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV 0.023 0.1 -10000 0 -0.24 27 27
NR4A1 0.012 0.074 0.2 15 -0.22 22 37
GSK3B 0.04 0.009 -10000 0 0 23 23
positive T cell selection 0.025 0.015 -10000 0 -10000 0 0
NFAT1/CK1 alpha 0.021 0.049 0.12 9 -0.19 12 21
RCH1/ KPNB1 0.036 0.062 -10000 0 -0.14 58 58
YWHAQ 0.04 0.007 -10000 0 0 18 18
PRKACA 0.035 0.015 -10000 0 0 84 84
AKAP5 0.04 0.007 -10000 0 0 14 14
MEF2D 0.041 0.008 -10000 0 0 18 18
mol:FK506 0 0 -10000 0 -10000 0 0
YWHAZ 0.034 0.016 -10000 0 0 96 96
NFATc/p38 alpha 0.03 0.11 0.28 5 -0.31 17 22
CREBBP 0.038 0.013 -10000 0 0 53 53
BCL2 0.036 0.014 -10000 0 0 67 67
Signaling events mediated by HDAC Class I

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
NF kappa B/RelA 0.053 0.094 -10000 0 -0.2 39 39
Ran/GTP/Exportin 1/HDAC1 -0.029 0.032 -10000 0 -0.12 45 45
NF kappa B1 p50/RelA/I kappa B alpha 0.022 0.1 0.24 1 -0.28 35 36
SUMO1 0.04 0.007 -10000 0 0 14 14
ZFPM1 0.035 0.015 -10000 0 0 86 86
NPC/RanGAP1/SUMO1/Ubc9 0.009 0.034 -10000 0 -0.14 25 25
FKBP3 0.039 0.009 -10000 0 0 30 30
Histones 0.069 0.085 0.24 1 -0.24 13 14
YY1/LSF 0.01 0.084 -10000 0 -0.23 42 42
SMG5 0 0 -10000 0 -10000 0 0
RAN 0.04 0.008 -10000 0 0 21 21
I kappa B alpha/HDAC3 0.016 0.059 -10000 0 -0.18 38 38
I kappa B alpha/HDAC1 0.029 0.088 0.21 1 -0.23 44 45
SAP18 0.039 0.008 -10000 0 0 24 24
RELA 0.015 0.083 0.23 2 -0.25 24 26
HDAC1/Smad7 0.063 0.051 -10000 0 -0.12 31 31
RANGAP1 0.037 0.012 -10000 0 0 54 54
HDAC3/TR2 0.045 0.061 0.21 1 -0.23 14 15
NuRD/MBD3 Complex 0.008 0.094 -10000 0 -0.29 30 30
NF kappa B1 p50/RelA 0.019 0.1 0.22 2 -0.27 38 40
EntrezGene:23225 0 0 -10000 0 -10000 0 0
GATA2 0.039 0.01 -10000 0 0 31 31
GATA1 0.041 0.002 -10000 0 0 1 1
Mad/Max 0.058 0.013 -10000 0 -10000 0 0
NuRD/MBD3 Complex/GATA1/Fog1 -0.002 0.1 -10000 0 -0.27 43 43
RBBP7 0.039 0.009 -10000 0 0 25 25
NPC 0.019 0.022 -10000 0 -0.083 23 23
RBBP4 0.038 0.011 -10000 0 0 40 40
MAX 0.04 0.006 -10000 0 0 12 12
EntrezGene:9972 0 0 -10000 0 -10000 0 0
FBXW11 0.04 0.008 -10000 0 0 22 22
NFKBIA 0.01 0.066 -10000 0 -0.26 28 28
KAT2B 0 0 -10000 0 -10000 0 0
mol:GTP 0 0 -10000 0 -10000 0 0
SIN3/HDAC complex 0.009 0.084 -10000 0 -0.27 26 26
SIN3 complex 0.076 0.053 -10000 0 -0.11 12 12
SMURF1 0.04 0.006 -10000 0 0 13 13
CHD3 0.037 0.013 -10000 0 0 56 56
SAP30 0.038 0.011 -10000 0 0 46 46
EntrezGene:23636 0 0 -10000 0 -10000 0 0
NCOR1 0.037 0.013 -10000 0 0 58 58
YY1/HDAC3 0.015 0.077 -10000 0 -0.24 27 27
YY1/HDAC2 0.013 0.078 -10000 0 -0.22 39 39
YY1/HDAC1 0.01 0.08 -10000 0 -0.22 39 39
NuRD/MBD2 Complex (MeCP1) 0.01 0.095 -10000 0 -0.29 30 30
PPARG 0.027 0.066 0.25 2 -0.2 26 28
HDAC8/hEST1B 0.041 0.035 -10000 0 -0.11 20 20
UBE2I 0.039 0.009 -10000 0 0 27 27
beta TrCP1/SCF ubiquitin ligase complex 0.039 0.008 -10000 0 0 22 22
TNFRSF1A 0.036 0.014 -10000 0 0 72 72
HDAC3/SMRT (N-CoR2) 0.046 0.06 0.21 1 -0.22 13 14
MBD3L2 0.038 0.011 -10000 0 0 43 43
ubiquitin-dependent protein catabolic process 0.063 0.051 -10000 0 -0.12 31 31
CREBBP 0.037 0.012 -10000 0 0 53 53
NuRD/MBD3/MBD3L2 Complex 0.004 0.11 0.18 8 -0.27 46 54
HDAC1 0.038 0.012 -10000 0 0 49 49
HDAC3 0.023 0.031 -10000 0 -0.24 4 4
HDAC2 0.038 0.01 -10000 0 0 38 38
YY1 0.005 0.056 -10000 0 -0.24 23 23
HDAC8 0.039 0.009 -10000 0 0 26 26
SMAD7 0.038 0.01 -10000 0 0 36 36
NCOR2 0.039 0.01 -10000 0 0 31 31
MXD1 0.04 0.007 -10000 0 0 15 15
STAT3 0.008 0.067 -10000 0 -0.24 33 33
NFKB1 0.036 0.013 -10000 0 0 66 66
EntrezGene:8021 0 0 -10000 0 -10000 0 0
RANBP2 0.039 0.009 -10000 0 0 30 30
YY1/LSF/HDAC1 0.021 0.093 -10000 0 -0.22 46 46
YY1/SAP30/HDAC1 0.024 0.086 -10000 0 -0.2 40 40
EP300 0.036 0.014 -10000 0 0 69 69
STAT3 (dimer non-phopshorylated) 0.008 0.066 -10000 0 -0.24 33 33
proteasomal ubiquitin-dependent protein catabolic process 0.01 0.066 -10000 0 -0.26 28 28
histone deacetylation 0.011 0.095 0.17 5 -0.29 30 35
STAT3 (dimer non-phopshorylated)/HDAC3 0.018 0.083 -10000 0 -0.28 22 22
nuclear export -0.041 0.035 0.11 20 -10000 0 20
PRKACA 0.035 0.015 -10000 0 0 84 84
GATAD2B 0.038 0.011 -10000 0 0 41 41
GATAD2A 0.037 0.012 -10000 0 0 54 54
GATA2/HDAC3 0.046 0.059 0.21 1 -0.21 15 16
GATA1/HDAC1 0.05 0.041 -10000 0 -0.13 24 24
GATA1/HDAC3 0.049 0.06 0.21 1 -0.21 17 18
CHD4 0.036 0.014 -10000 0 0 69 69
TNF-alpha/TNFR1A 0.047 0.038 -10000 0 -0.13 16 16
SIN3/HDAC complex/Mad/Max 0.015 0.08 -10000 0 -0.26 23 23
NuRD Complex 0.001 0.11 0.18 7 -0.28 40 47
positive regulation of chromatin silencing 0.065 0.082 0.23 1 -0.24 13 14
SIN3B 0.036 0.014 -10000 0 0 67 67
MTA2 0.04 0.006 -10000 0 0 10 10
SIN3A 0.039 0.009 -10000 0 0 30 30
XPO1 0.039 0.01 -10000 0 0 35 35
SUMO1/HDAC1 0.034 0.066 -10000 0 -0.18 25 25
HDAC complex 0.073 0.074 -10000 0 -0.13 51 51
GATA1/Fog1 0.051 0.022 -10000 0 -10000 0 0
FKBP25/HDAC1/HDAC2 0.058 0.06 -10000 0 -0.13 41 41
TNF 0.04 0.008 -10000 0 0 22 22
negative regulation of cell growth 0.015 0.081 0.17 1 -0.26 24 25
NuRD/MBD2/PRMT5 Complex 0.01 0.095 -10000 0 -0.29 30 30
Ran/GTP/Exportin 1 0.035 0.071 -10000 0 -0.18 36 36
NF kappa B/RelA/I kappa B alpha 0.005 0.078 -10000 0 -0.26 31 31
SIN3/HDAC complex/NCoR1 0.001 0.093 -10000 0 -0.24 44 44
TFCP2 0.039 0.01 -10000 0 0 35 35
NR2C1 0.039 0.01 -10000 0 0 33 33
MBD3 0.036 0.014 -10000 0 0 69 69
MBD2 0.039 0.01 -10000 0 0 32 32
Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4 0.038 0.011 -10000 0 0 43 43
SMAD2 0.012 0.052 0.19 7 -0.23 3 10
SMAD3 0.014 0.054 0.28 1 -0.3 4 5
SMAD3/SMAD4 -0.015 0.16 -10000 0 -0.39 78 78
SMAD4/Ubc9/PIASy 0.065 0.041 -10000 0 -0.13 9 9
SMAD2/SMAD2/SMAD4 0.053 0.083 0.27 1 -0.18 9 10
PPM1A 0.04 0.006 -10000 0 0 10 10
CALM1 0.039 0.009 -10000 0 0 26 26
SMAD2/SMAD4 0.03 0.051 0.22 2 -0.18 7 9
MAP3K1 0.036 0.013 -10000 0 0 63 63
TRAP-1/SMAD4 0.049 0.041 -10000 0 -0.14 21 21
MAPK3 0.04 0.007 -10000 0 0 18 18
MAPK1 0.038 0.011 -10000 0 0 44 44
NUP214 0.038 0.011 -10000 0 0 43 43
CTDSP1 0.04 0.007 -10000 0 0 15 15
CTDSP2 0.039 0.009 -10000 0 0 29 29
CTDSPL 0.04 0.007 -10000 0 0 15 15
KPNB1 0.039 0.009 -10000 0 0 25 25
TGFBRAP1 0.04 0.008 -10000 0 0 20 20
UBE2I 0.039 0.009 -10000 0 0 27 27
NUP153 0.037 0.013 -10000 0 0 57 57
KPNA2 0.035 0.014 -10000 0 0 79 79
PIAS4 0.037 0.012 -10000 0 0 54 54
Atypical NF-kappaB 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 Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
BCL3/RelA 0.053 0.025 -10000 0 -0.13 4 4
FBXW11 0.04 0.008 -10000 0 0 22 22
NF kappa B1 p50/c-Rel 0.028 0.036 -10000 0 -0.12 26 26
NF kappa B1 p50/RelA/I kappa B alpha 0.019 0.077 0.26 1 -0.22 21 22
NFKBIA 0.003 0.06 -10000 0 -0.15 53 53
MAPK14 0.04 0.008 -10000 0 0 20 20
NF kappa B1 p105/p50 0.027 0.039 -10000 0 -0.13 27 27
ARRB2 0.014 0.028 -10000 0 -0.2 9 9
REL 0.04 0.007 -10000 0 0 15 15
response to oxidative stress 0 0 -10000 0 -10000 0 0
BCL3/NF kappa B1 p50 0.027 0.035 -10000 0 -0.12 23 23
response to UV 0 0 -10000 0 -10000 0 0
NF kappa B1 p105/RelA 0.028 0.038 -10000 0 -0.12 29 29
PIK3CA 0.029 0.019 -10000 0 0 166 166
NF kappa B1 p50 dimer 0.019 0.039 -10000 0 -0.14 28 28
PIK3R1 0.034 0.016 -10000 0 0 99 99
NFKB1 -0.017 0.008 -10000 0 -10000 0 0
RELA 0.04 0.006 -10000 0 0 10 10
positive regulation of anti-apoptosis 0.012 0.051 0.14 1 -0.18 12 13
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2 0.018 0.081 0.23 1 -0.22 24 25
SRC 0.039 0.009 -10000 0 0 28 28
PI3K 0.023 0.06 -10000 0 -0.15 44 44
NF kappa B1 p50/RelA 0.012 0.051 0.14 1 -0.18 12 13
IKBKB 0.038 0.011 -10000 0 0 41 41
beta TrCP1/SCF ubiquitin ligase complex 0.039 0.008 -10000 0 0 22 22
SYK 0.036 0.014 -10000 0 0 67 67
I kappa B alpha/PIK3R1 0.016 0.068 0.27 1 -0.24 12 13
cell death 0.017 0.078 0.22 1 -0.22 24 25
NF kappa B1 p105/c-Rel 0.028 0.036 -10000 0 -0.12 26 26
LCK 0.039 0.009 -10000 0 0 25 25
BCL3 0.037 0.012 -10000 0 0 51 51
Glucocorticoid receptor regulatory network

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
PCK2 -0.02 0.076 -10000 0 -0.39 10 10
SMARCC2 0.039 0.009 -10000 0 0 29 29
SMARCC1 0.04 0.007 -10000 0 0 18 18
TBX21 0.04 0.06 0.41 2 -0.26 1 3
SUMO2 0.037 0.015 -10000 0 -0.014 36 36
STAT1 (dimer) 0.022 0.064 -10000 0 -0.18 45 45
FKBP4 0.036 0.014 -10000 0 0 73 73
FKBP5 0.03 0.018 -10000 0 0 142 142
GR alpha/HSP90/FKBP51/HSP90 -0.034 0.074 0.21 3 -0.21 17 20
PRL 0.044 0.063 -10000 0 -10000 0 0
cortisol/GR alpha (dimer)/TIF2 -0.056 0.12 0.4 4 -0.34 2 6
RELA 0.012 0.095 -10000 0 -0.16 117 117
FGG -0.053 0.11 0.35 4 -0.32 1 5
GR beta/TIF2 -0.032 0.08 0.25 2 -0.24 6 8
IFNG 0.045 0.1 -10000 0 -0.41 1 1
apoptosis -0.053 0.17 -10000 0 -0.41 75 75
CREB1 0.048 0.009 -10000 0 -10000 0 0
histone acetylation 0.023 0.079 0.33 6 -0.39 6 12
BGLAP 0.045 0.083 -10000 0 -0.88 2 2
GR/PKAc 0.031 0.083 0.3 1 -0.15 22 23
NF kappa B1 p50/RelA 0.011 0.17 -10000 0 -0.29 115 115
SMARCD1 0.04 0.007 -10000 0 0 17 17
MDM2 -0.013 0.047 0.13 7 -0.24 8 15
GATA3 0.049 0.013 -10000 0 -10000 0 0
AKT1 0.035 0.015 0.17 2 -0.048 6 8
CSF2 0.012 0.052 -10000 0 -10000 0 0
GSK3B 0.037 0.014 -10000 0 -0.012 38 38
NR1I3 -0.045 0.15 -10000 0 -0.41 29 29
CSN2 -0.049 0.096 0.28 6 -0.3 2 8
BRG1/BAF155/BAF170/BAF60A 0.074 0.065 -10000 0 -0.13 30 30
NFATC1 0.043 0.017 -10000 0 -10000 0 0
POU2F1 0.045 0.008 -10000 0 -10000 0 0
CDKN1A -0.043 0.12 -10000 0 -10000 0 0
response to stress 0 0 -10000 0 -10000 0 0
response to UV -0.001 0.004 -10000 0 -10000 0 0
SFN 0.035 0.015 -10000 0 0 83 83
GR alpha/HSP90/FKBP51/HSP90/14-3-3 -0.03 0.079 0.23 2 -0.2 24 26
prolactin receptor activity 0 0 -10000 0 -10000 0 0
EGR1 -0.1 0.28 -10000 0 -0.7 89 89
JUN 0.04 0.096 0.33 8 -0.28 4 12
IL4 0.042 0.057 -10000 0 -10000 0 0
CDK5R1 0.038 0.011 -10000 0 0 40 40
PRKACA 0.035 0.015 -10000 0 0 84 84
cortisol/GR alpha (monomer)/AP-1 -0.039 0.067 0.2 11 -0.22 23 34
GR alpha/HSP90/FKBP51/HSP90/PP5C -0.024 0.079 0.24 2 -0.2 17 19
cortisol/GR alpha (monomer) -0.069 0.13 0.42 5 -0.4 1 6
NCOA2 0.037 0.013 -10000 0 0 60 60
response to hypoxia 0 0 -10000 0 -10000 0 0
FOS 0.032 0.055 -10000 0 -0.13 29 29
AP-1/NFAT1-c-4 0.038 0.14 -10000 0 -0.38 18 18
AFP 0.03 0.094 -10000 0 -10000 0 0
SUV420H1 0.039 0.009 -10000 0 0 30 30
IRF1 -0.1 0.22 -10000 0 -0.57 82 82
TP53 0.035 0.028 -10000 0 -10000 0 0
PPP5C 0.039 0.009 -10000 0 0 27 27
KRT17 0.028 0.16 -10000 0 -0.77 11 11
KRT14 0.023 0.19 0.5 8 -1.1 12 20
TBP 0.043 0.027 -10000 0 -0.32 2 2
CREBBP 0.03 0.054 0.33 13 -10000 0 13
HDAC1 0.033 0.012 -10000 0 -0.058 2 2
HDAC2 0.037 0.01 -10000 0 -10000 0 0
AP-1 0.038 0.14 -10000 0 -0.38 18 18
MAPK14 0.037 0.015 -10000 0 -0.015 39 39
MAPK10 0.033 0.02 -10000 0 -0.009 90 90
MAPK11 0.027 0.021 -10000 0 -0.002 170 170
KRT5 -0.01 0.26 -10000 0 -0.83 43 43
interleukin-1 receptor activity -0.001 0 -10000 0 -10000 0 0
NCOA1 0.04 0.011 -10000 0 -0.068 2 2
STAT1 0.022 0.064 -10000 0 -0.18 45 45
CGA 0.045 0.065 0.3 1 -10000 0 1
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2 -0.059 0.11 0.3 4 -0.34 37 41
MAPK3 0.035 0.019 -10000 0 -0.019 52 52
MAPK1 0.035 0.017 -10000 0 -0.01 65 65
ICAM1 -0.079 0.32 -10000 0 -0.77 89 89
NFKB1 0.006 0.11 -10000 0 -0.19 111 111
MAPK8 0.049 0.083 0.48 2 -0.26 3 5
MAPK9 0.035 0.017 -10000 0 -0.01 59 59
cortisol/GR alpha (dimer) -0.056 0.18 -10000 0 -0.42 79 79
BAX -0.05 0.12 -10000 0 -10000 0 0
POMC 0.052 0.092 0.49 2 -10000 0 2
EP300 0.028 0.047 0.32 10 -10000 0 10
cortisol/GR alpha (dimer)/p53 -0.073 0.12 0.41 4 -0.36 1 5
proteasomal ubiquitin-dependent protein catabolic process -0.026 0.047 0.25 5 -0.22 8 13
SGK1 -0.025 0.11 0.34 10 -0.3 47 57
IL13 0.047 0.094 -10000 0 -10000 0 0
IL6 0.011 0.16 -10000 0 -0.64 15 15
PRKACG 0.04 0.008 -10000 0 0 22 22
IL5 0.046 0.096 -10000 0 -10000 0 0
IL2 0.037 0.12 -10000 0 -0.53 6 6
CDK5 0.035 0.014 -10000 0 0 69 69
PRKACB 0.038 0.011 -10000 0 0 44 44
HSP90AA1 0 0 -10000 0 -10000 0 0
IL8 -0.013 0.22 -10000 0 -0.8 32 32
CDK5R1/CDK5 0.044 0.04 -10000 0 -0.13 19 19
NF kappa B1 p50/RelA/PKAc 0.042 0.15 -10000 0 -0.22 91 91
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90 -0.043 0.11 0.37 5 -0.31 1 6
SMARCA4 0.034 0.015 -10000 0 0 92 92
chromatin remodeling -0.03 0.091 0.27 4 -0.36 10 14
NF kappa B1 p50/RelA/Cbp 0.025 0.16 0.41 6 -0.25 102 108
JUN (dimer) 0.04 0.096 0.33 8 -0.28 4 12
YWHAH 0.038 0.011 -10000 0 0 46 46
VIPR1 0.041 0.057 0.4 1 -0.26 1 2
NR3C1 -0.044 0.091 0.3 3 -0.32 3 6
NR4A1 0.038 0.018 -10000 0 -10000 0 0
TIF2/SUV420H1 0.042 0.051 -10000 0 -0.14 36 36
MAPKKK cascade -0.053 0.17 -10000 0 -0.41 75 75
cortisol/GR alpha (dimer)/Src-1 -0.052 0.13 0.4 5 -0.34 1 6
PBX1 0.043 0.012 -10000 0 -10000 0 0
POU1F1 0.046 0.008 -10000 0 -10000 0 0
SELE 0.023 0.11 -10000 0 -0.4 4 4
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A -0.03 0.091 0.27 4 -0.36 10 14
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90 -0.043 0.11 0.37 5 -0.31 1 6
mol:cortisol -0.042 0.066 0.21 7 -10000 0 7
MMP1 0.008 0.16 -10000 0 -0.75 19 19
Signaling events regulated by Ret tyrosine kinase

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
PTK2 0.016 0.088 -10000 0 -0.38 23 23
Crk/p130 Cas/Paxillin 0.005 0.037 -10000 0 -0.18 4 4
JUN 0.002 0.062 0.19 4 -0.23 13 17
HRAS 0.039 0.01 -10000 0 0 31 31
RET51/GFRalpha1/GDNF/GRB10 0.088 0.039 -10000 0 -0.11 5 5
RAP1A 0.039 0.01 -10000 0 0 35 35
FRS2 0.038 0.011 -10000 0 0 41 41
RAP1A/GDP 0.023 0.031 -10000 0 -0.12 22 22
RET51/GFRalpha1/GDNF/DOK1 0.088 0.039 -10000 0 -0.11 5 5
EntrezGene:5979 0 0 -10000 0 -10000 0 0
PTPN11 0.039 0.009 -10000 0 0 29 29
mol:GTP 0 0 -10000 0 -10000 0 0
CRK 0.038 0.012 -10000 0 0 49 49
RET9/GFRalpha1/GDNF/Enigma 0.064 0.033 -10000 0 -0.1 2 2
RHOA 0.04 0.006 -10000 0 0 13 13
RAP1A/GTP 0.075 0.05 -10000 0 -0.1 15 15
GRB7 0.037 0.013 -10000 0 0 57 57
RET51/GFRalpha1/GDNF 0.078 0.045 -10000 0 -0.11 3 3
MAPKKK cascade 0.032 0.046 -10000 0 -0.14 3 3
BCAR1 0.036 0.013 -10000 0 0 65 65
RET9/GFRalpha1/GDNF/IRS1 0.063 0.034 -10000 0 -0.1 5 5
lamellipodium assembly 0.03 0.05 -10000 0 -0.18 3 3
RET51/GFRalpha1/GDNF/SHC 0.088 0.036 -10000 0 -0.11 1 1
PIK3CA 0.029 0.019 -10000 0 0 166 166
RET9/GFRalpha1/GDNF/SHC 0.064 0.033 -10000 0 -0.1 2 2
RET9/GFRalpha1/GDNF/Shank3 0.05 0.039 -10000 0 -0.1 1 1
MAPK3 -0.009 0.063 0.18 38 -10000 0 38
DOK1 0.04 0.008 -10000 0 0 22 22
DOK6 0.038 0.011 -10000 0 0 45 45
PXN 0.04 0.006 -10000 0 0 10 10
neurite development 0 0.059 0.22 13 -0.2 4 17
DOK5 0.022 0.021 -10000 0 0 260 260
GFRA1 0.037 0.012 -10000 0 0 54 54
MAPK8 0.013 0.059 0.2 1 -0.23 10 11
HRAS/GTP 0.08 0.046 -10000 0 -0.15 3 3
tube development 0.047 0.043 0.24 9 -0.1 2 11
MAPK1 -0.01 0.061 0.18 34 -10000 0 34
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2 0.02 0.046 -10000 0 -0.17 24 24
Rac1/GDP 0.029 0.009 -10000 0 -0.12 1 1
SRC 0.039 0.009 -10000 0 0 28 28
PDLIM7 0.039 0.009 -10000 0 0 30 30
RET51/GFRalpha1/GDNF/Dok6 0.093 0.052 -10000 0 -0.11 1 1
SHC1 0.039 0.008 -10000 0 0 23 23
RET51/GFRalpha1/GDNF/Dok4 0.086 0.039 -10000 0 -0.11 1 1
RET51/GFRalpha1/GDNF/Dok5 0.039 0.078 -10000 0 -0.11 88 88
PRKCA 0.035 0.015 -10000 0 0 86 86
HRAS/GDP 0.029 0.007 -10000 0 -10000 0 0
CREB1 0.036 0.06 -10000 0 -0.37 4 4
PIK3R1 0.034 0.016 -10000 0 0 99 99
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2 0.024 0.032 -10000 0 -0.14 11 11
RET51/GFRalpha1/GDNF/Grb7 0.083 0.044 -10000 0 -0.11 6 6
mol:GDP 0 0 -10000 0 -10000 0 0
RET 0.039 0.008 -10000 0 0 23 23
DOK4 0.038 0.01 -10000 0 0 37 37
JNK cascade 0.002 0.062 0.18 6 -0.22 13 19
RET9/GFRalpha1/GDNF/FRS2 0.059 0.04 -10000 0 -0.1 11 11
SHANK3 0.03 0.018 -10000 0 0 152 152
RASA1 0.037 0.013 -10000 0 0 56 56
NCK1 0.036 0.014 -10000 0 0 70 70
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1 0.023 0.037 -10000 0 -0.14 22 22
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2 0.026 0.048 -10000 0 -0.17 24 24
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK 0.018 0.056 -10000 0 -0.16 35 35
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1 0.029 0.039 -10000 0 -0.15 19 19
PI3K 0.045 0.064 0.22 8 -0.25 2 10
SOS1 0.037 0.012 -10000 0 0 51 51
RET9/GFRalpha1/GDNF/Shank3/Grb2 0.062 0.047 -10000 0 -0.1 2 2
GRB10 0.04 0.008 -10000 0 0 22 22
activation of MAPKK activity 0.029 0.052 -10000 0 -0.31 5 5
RET51/GFRalpha1/GDNF/FRS2 0.083 0.046 -10000 0 -0.11 11 11
GAB1 0.037 0.013 -10000 0 0 58 58
IRS1 0.04 0.008 -10000 0 0 22 22
IRS2 0.039 0.009 -10000 0 0 30 30
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2 0.029 0.034 -10000 0 -0.17 1 1
RET51/GFRalpha1/GDNF/PKC alpha 0.075 0.057 -10000 0 -0.11 30 30
GRB2 0.04 0.008 -10000 0 0 21 21
PRKACA 0.035 0.015 -10000 0 0 84 84
GDNF 0.039 0.01 -10000 0 0 35 35
RAC1 0.039 0.009 -10000 0 0 28 28
RET51/GFRalpha1/GDNF/IRS1 0.088 0.038 -10000 0 -0.11 5 5
Rac1/GTP 0.044 0.063 0.2 4 -0.22 3 7
RET9/GFRalpha1/GDNF 0.047 0.021 -10000 0 -0.11 1 1
GFRalpha1/GDNF 0.051 0.024 -10000 0 -0.13 1 1
Sphingosine 1-phosphate (S1P) pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
SPHK2 0.04 0.008 -10000 0 0 20 20
SPHK1 0.039 0.008 -10000 0 0 24 24
GNAI2 0.04 0.006 -10000 0 0 13 13
mol:S1P 0.015 0.025 -10000 0 -0.17 9 9
GNAO1 0.035 0.015 -10000 0 0 85 85
mol:Sphinganine-1-P -0.019 0.006 -10000 0 -10000 0 0
growth factor activity 0 0 -10000 0 -10000 0 0
S1P/S1P2/G12/G13 0.05 0.048 -10000 0 -0.16 10 10
GNAI3 0.038 0.011 -10000 0 0 45 45
G12/G13 0.053 0.028 -10000 0 -0.13 8 8
S1PR3 0 0 -10000 0 -10000 0 0
S1PR2 0 0 -10000 0 -10000 0 0
EDG1 0.04 0.006 -10000 0 0 11 11
S1P1/S1P 0.036 0.043 0.16 1 -0.12 35 36
S1PR5 0 0 -10000 0 -10000 0 0
S1PR4 0 0 -10000 0 -10000 0 0
GNAI1 0.034 0.015 -10000 0 0 93 93
S1P/S1P5/G12 0.031 0.039 -10000 0 -0.14 10 10
S1P/S1P3/Gq 0.016 0.074 0.17 1 -0.24 35 36
S1P/S1P4/Gi -0.009 0.091 0.15 1 -0.2 68 69
GNAQ 0.038 0.012 -10000 0 0 48 48
GNAZ 0.038 0.011 -10000 0 0 46 46
GNA14 0.039 0.009 -10000 0 0 29 29
GNA15 0.036 0.014 -10000 0 0 68 68
GNA12 0.039 0.01 -10000 0 0 33 33
GNA13 0.039 0.008 -10000 0 0 23 23
GNA11 0.037 0.013 -10000 0 0 61 61
ABCC1 0.039 0.009 -10000 0 0 27 27
Insulin Pathway

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
CBL/APS/CAP 0.059 0.041 -10000 0 -0.12 10 10
TC10/GTP 0.051 0.035 -10000 0 -0.1 11 11
Insulin Receptor/Insulin/IRS1/Shp2 0.086 0.058 -10000 0 -0.12 22 22
HRAS 0.039 0.01 -10000 0 0 31 31
APS homodimer 0 0 -10000 0 -10000 0 0
GRB14 0.038 0.012 -10000 0 0 49 49
FOXO3 -0.004 0.009 0.022 12 -0.036 6 18
AKT1 0.022 0.1 0.21 56 -0.17 3 59
INSR 0.041 0.016 0.081 10 -0.049 1 11
Insulin Receptor/Insulin 0.084 0.058 0.24 37 -0.14 4 41
mol:GTP 0 0 -10000 0 -10000 0 0
GRB10 0.04 0.008 -10000 0 0 22 22
SORBS1 0.039 0.009 -10000 0 0 30 30
CRK 0.038 0.012 -10000 0 0 49 49
PTPN1 -0.007 0.04 0.15 28 -0.24 1 29
CAV1 -0.007 0.042 0.17 17 -10000 0 17
CBL/APS/CAP/Crk-II/C3G 0.08 0.04 -10000 0 -0.1 6 6
Insulin Receptor/Insulin/IRS1/NCK2 0.093 0.046 -10000 0 -0.1 9 9
mol:GDP 0 0 -10000 0 -10000 0 0
mol:PI-3-4-5-P3 0.037 0.063 -10000 0 -0.11 44 44
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B 0.023 0.097 0.22 1 -0.31 36 37
RPS6KB1 0.012 0.093 0.16 126 -0.18 8 134
PARD6A 0.037 0.013 -10000 0 0 61 61
CBL 0.04 0.008 -10000 0 0 20 20
tumor necrosis factor-mediated signaling pathway 0 0 -10000 0 -10000 0 0
DOK1 0.023 0.078 -10000 0 -0.7 6 6
PIK3R1 0.034 0.016 -10000 0 0 99 99
Insulin Receptor/Insuli/IRS1/GRB2/Shc 0.054 0.083 0.2 25 -0.18 11 36
HRAS/GTP -0.026 0.032 0.049 2 -0.11 19 21
Insulin Receptor 0.041 0.015 0.081 10 -0.049 1 11
Insulin Receptor/Insuli/IRS1/GRB2/SHC 0.1 0.06 -10000 0 -0.11 9 9
PRKCI -0.013 0.14 -10000 0 -0.37 61 61
Insulin Receptor/Insulin/GRB14/PDK1 0.017 0.051 -10000 0 -0.12 41 41
SHC1 0.039 0.008 -10000 0 0 23 23
negative regulation of MAPKKK cascade 0.049 0.079 -10000 0 -0.53 6 6
PI3K 0.047 0.071 -10000 0 -0.11 44 44
NCK2 0.041 0.004 -10000 0 0 6 6
RHOQ 0.039 0.009 -10000 0 0 25 25
mol:H2O2 -0.002 0.004 0.019 1 -0.032 1 2
HRAS/GDP 0.029 0.007 -10000 0 -10000 0 0
AKT2 0.018 0.094 0.2 47 -0.17 3 50
PRKCZ 0.025 0.11 -10000 0 -0.33 41 41
SH2B2 0 0 -10000 0 -10000 0 0
SHC/SHIP -0.008 0.04 0.16 16 -0.12 1 17
F2RL2 0.036 0.013 -10000 0 0 63 63
TRIP10 0.038 0.012 -10000 0 0 49 49
Insulin Receptor/Insulin/Shc 0.07 0.037 -10000 0 -0.1 5 5
TC10/GTP/CIP4/Exocyst 0.046 0.029 -10000 0 -0.11 12 12
Insulin Receptor/Insulin/SHC/GRB2/Sos1 0.092 0.069 -10000 0 -0.12 20 20
RAPGEF1 0.039 0.009 -10000 0 0 26 26
RASA1 0.037 0.013 -10000 0 0 56 56
NCK1 0.036 0.014 -10000 0 0 70 70
CBL/APS/CAP/Crk-II 0.065 0.034 -10000 0 -0.11 6 6
TC10/GDP 0.027 0.019 -10000 0 -0.12 8 8
Insulin Receptor/Insulin/SHC/GRB10 0.089 0.051 -10000 0 -0.1 11 11
INPP5D -0.013 0.017 0.053 11 -0.091 8 19
SOS1 0.037 0.012 -10000 0 0 51 51
SGK1 -0.004 0.004 -10000 0 -10000 0 0
mol:cAMP 0 0 -10000 0 -10000 0 0
PTPN11 0.039 0.009 -10000 0 0 29 29
IRS1 0.04 0.008 -10000 0 0 22 22
p62DOK/RasGAP 0.05 0.079 -10000 0 -0.54 6 6
INS 0.043 0.014 0.082 13 -0.002 31 44
mol:PI-3-4-P2 -0.013 0.017 0.053 11 -0.09 8 19
GRB2 0.04 0.008 -10000 0 0 21 21
EIF4EBP1 0.009 0.085 0.15 111 -0.16 3 114
PTPRA 0.042 0.013 0.083 3 -0.049 1 4
PIK3CA 0.029 0.019 -10000 0 0 166 166
TC10/GTP/CIP4 0.046 0.029 -10000 0 -0.11 12 12
PDPK1 0.039 0.009 -10000 0 0 29 29
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos 0.02 0.055 -10000 0 -0.16 27 27
Insulin Receptor/Insulin/IRS1 0.069 0.038 -10000 0 -0.099 8 8
Insulin Receptor/Insulin/IRS3 0.058 0.031 -10000 0 -0.12 4 4
Par3/Par6 0.069 0.049 -10000 0 -0.098 14 14
Class IB PI3K non-lipid kinase events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
cAMP biosynthetic process -0.039 0.009 0 28 -9999 0 28
PI3K Class IB/PDE3B 0.039 0.009 -9999 0 0 28 28
PDE3B 0.039 0.009 -9999 0 0 28 28
Coregulation of Androgen receptor activity

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
NRIP1 0.035 0.016 -9999 0 -10000 0 0
SVIL 0.036 0.015 -9999 0 -10000 0 0
ZNF318 0.037 0.009 -9999 0 -0.032 2 2
JMJD2C 0.041 0.016 -9999 0 -10000 0 0
T-DHT/AR/Ubc9 0.037 0.06 -9999 0 -0.1 74 74
CARM1 0.036 0.014 -9999 0 0 71 71
PRDX1 0.039 0.009 -9999 0 0 31 31
PELP1 0.038 0.011 -9999 0 0 39 39
CTNNB1 0.04 0.01 -9999 0 -10000 0 0
AKT1 0.038 0.01 -9999 0 0 34 34
PTK2B 0.034 0.016 -9999 0 -10000 0 0
MED1 -0.001 0 -9999 0 -10000 0 0
MAK 0.033 0.014 -9999 0 -0.032 2 2
response to oxidative stress 0 0 -9999 0 -10000 0 0
HIP1 0.04 0.01 -9999 0 -10000 0 0
GSN 0.039 0.011 -9999 0 -10000 0 0
NCOA2 0.037 0.013 -9999 0 0 60 60
NCOA6 0.039 0.011 -9999 0 -10000 0 0
DNA-PK 0.049 0.067 -9999 0 -0.14 47 47
NCOA4 0.039 0.009 -9999 0 0 26 26
PIAS3 0.038 0.012 -9999 0 -10000 0 0
cell proliferation 0.019 0.042 -9999 0 -0.44 4 4
XRCC5 0.038 0.011 -9999 0 0 41 41
UBE3A 0.04 0.01 -9999 0 -10000 0 0
T-DHT/AR/SNURF 0.034 0.062 -9999 0 -0.11 74 74
FHL2 0.026 0.061 -9999 0 -0.58 4 4
RANBP9 0.039 0.012 -9999 0 -10000 0 0
JMJD1A 0.051 0.018 -9999 0 -0.14 1 1
CDK6 0.032 0.017 -9999 0 0 126 126
TGFB1I1 0.041 0.006 -9999 0 -10000 0 0
T-DHT/AR/CyclinD1 0.013 0.077 -9999 0 -0.12 125 125
XRCC6 0.036 0.014 -9999 0 0 69 69
T-DHT/AR 0.037 0.056 -9999 0 -0.099 68 68
CTDSP1 0.04 0.007 -9999 0 0 15 15
CTDSP2 0.038 0.009 -9999 0 -10000 0 0
BRCA1 0.035 0.016 -9999 0 -10000 0 0
TCF4 0.036 0.012 -9999 0 0 54 54
CDKN2A 0.028 0.019 -9999 0 0 167 167
SRF 0.043 0.019 -9999 0 -0.14 3 3
NKX3-1 0.014 0.083 -9999 0 -0.3 30 30
KLK3 0.004 0.048 -9999 0 -10000 0 0
TMF1 0.039 0.01 -9999 0 0 37 37
HNRNPA1 -0.001 0 -9999 0 -10000 0 0
AOF2 0.04 0.009 -9999 0 -10000 0 0
APPL1 -0.011 0.003 -9999 0 -10000 0 0
T-DHT/AR/Caspase 8 0.033 0.064 -9999 0 -0.11 86 86
AR 0.037 0.02 -9999 0 -0.042 1 1
UBA3 0 0 -9999 0 -10000 0 0
PATZ1 -0.001 0 -9999 0 -10000 0 0
PAWR 0.041 0.006 -9999 0 0 11 11
PRKDC 0.037 0.011 -9999 0 0 44 44
PA2G4 0.038 0.009 -9999 0 0 28 28
UBE2I 0.039 0.009 -9999 0 0 27 27
T-DHT/AR/Cyclin D3/CDK11 p58 0.034 0.056 -9999 0 -0.092 77 77
RPS6KA3 0.038 0.013 -9999 0 -10000 0 0
T-DHT/AR/ARA70 0.034 0.065 -9999 0 -0.1 88 88
LATS2 0.039 0.007 -9999 0 0 17 17
T-DHT/AR/PRX1 0.031 0.059 -9999 0 -0.094 88 88
Cyclin D3/CDK11 p58 0.028 0.015 -9999 0 -0.12 4 4
VAV3 0.034 0.017 -9999 0 -10000 0 0
KLK2 0.02 0.063 -9999 0 -0.3 16 16
CASP8 0.039 0.009 -9999 0 0 27 27
T-DHT/AR/TIF2/CARM1 0.043 0.07 -9999 0 -0.1 65 65
TMPRSS2 0.013 0.09 -9999 0 -0.31 34 34
CCND1 0.031 0.018 -9999 0 -10000 0 0
PIAS1 0.041 0.009 -9999 0 -10000 0 0
mol:T-DHT 0.005 0.005 -9999 0 -0.036 3 3
CDC2L1 0 0 -9999 0 -10000 0 0
PIAS4 0.039 0.013 -9999 0 -10000 0 0
T-DHT/AR/CDK6 0.017 0.075 -9999 0 -0.11 117 117
CMTM2 0.036 0.013 -9999 0 0 60 60
SNURF 0.038 0.011 -9999 0 0 45 45
ZMIZ1 0.005 0.005 -9999 0 -0.036 3 3
CCND3 0.039 0.01 -9999 0 0 31 31
TGIF1 -0.001 0 -9999 0 -10000 0 0
FKBP4 0.037 0.014 -9999 0 -10000 0 0
Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity -0.048 0.043 0.14 16 -10000 0 16
KIRREL 0.043 0.015 0.083 1 -10000 0 1
Nephrin/NEPH1Par3/Par6/Atypical PKCs 0.048 0.043 -10000 0 -0.14 16 16
PLCG1 0.038 0.011 -10000 0 0 43 43
ARRB2 0.038 0.011 -10000 0 0 46 46
WASL 0.04 0.007 -10000 0 0 18 18
Nephrin/NEPH1/podocin/CD2AP 0.073 0.067 -10000 0 -0.11 34 34
ChemicalAbstracts:57-88-5 0 0 -10000 0 -10000 0 0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP 0.021 0.05 0.14 1 -0.15 30 31
FYN 0.006 0.065 0.16 68 -0.12 14 82
mol:Ca2+ 0.075 0.06 -10000 0 -0.12 22 22
mol:DAG 0.076 0.061 0.21 1 -0.12 22 23
NPHS2 0.043 0.018 0.086 2 -0.042 15 17
mol:IP3 0.076 0.061 0.21 1 -0.12 22 23
regulation of endocytosis 0.053 0.056 -10000 0 -0.12 17 17
Nephrin/NEPH1/podocin/Cholesterol 0.062 0.047 0.18 1 -0.1 17 18
establishment of cell polarity 0.048 0.043 -10000 0 -0.14 16 16
Nephrin/NEPH1/podocin/NCK1-2 0.084 0.076 -10000 0 -0.11 37 37
Nephrin/NEPH1/beta Arrestin2 0.055 0.058 -10000 0 -0.12 17 17
NPHS1 0.037 0.021 0.085 4 -0.043 14 18
Nephrin/NEPH1/podocin 0.054 0.053 0.22 1 -0.12 15 16
TJP1 0.036 0.013 -10000 0 0 63 63
NCK1 0.036 0.014 -10000 0 0 70 70
NCK2 0.041 0.004 -10000 0 0 6 6
heterophilic cell adhesion 0 0 -10000 0 -10000 0 0
Nephrin/NEPH1/podocin/PLCgamma1 0.078 0.062 0.21 1 -0.12 22 23
CD2AP 0.037 0.013 -10000 0 0 62 62
Nephrin/NEPH1/podocin/GRB2 0.082 0.058 0.21 1 -0.12 16 17
GRB2 0.04 0.008 -10000 0 0 21 21
homophilic cell adhesion 0 0 -10000 0 -10000 0 0
TRPC6 0.008 0.07 0.17 76 -0.12 2 78
cytoskeleton organization 0.017 0.054 0.22 10 -0.17 11 21
Nephrin/NEPH1 0.041 0.033 -10000 0 -0.092 17 17
Nephrin/NEPH1/ZO-1 0.054 0.06 -10000 0 -0.13 34 34
Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer 0.056 0.049 -10000 0 -0.11 22 22
fibroblast growth factor receptor signaling pathway 0.055 0.049 -10000 0 -0.11 22 22
LAMA1 0.033 0.016 -10000 0 0 104 104
PRNP 0.036 0.013 -10000 0 0 63 63
GPC1/SLIT2 0.018 0.07 -10000 0 -0.13 87 87
SMAD2 -0.02 0.036 0.19 9 -10000 0 9
GPC1/PrPc/Cu2+ 0.04 0.041 -10000 0 -0.11 32 32
GPC1/Laminin alpha1 0.045 0.031 -10000 0 -0.13 6 6
TDGF1 0.04 0.006 -10000 0 0 13 13
CRIPTO/GPC1 0.056 0.018 -10000 0 -0.13 1 1
APP/GPC1 0.046 0.044 -10000 0 -0.13 27 27
mol:NO 0 0 -10000 0 -10000 0 0
YES1 -0.017 0.027 0.19 6 -0.12 1 7
FLT1 0.039 0.009 -10000 0 0 28 28
GPC1/TGFB/TGFBR1/TGFBR2 0.067 0.042 -10000 0 -0.11 17 17
SERPINC1 0.04 0.008 -10000 0 0 19 19
FYN -0.015 0.028 0.19 6 -0.12 1 7
FGR -0.018 0.027 0.19 6 -0.12 1 7
positive regulation of MAPKKK cascade 0.002 0.074 0.2 19 -0.18 25 44
SLIT2 0.028 0.019 -10000 0 0 176 176
GPC1/NRG 0.05 0.025 -10000 0 -0.13 1 1
NRG1 0.036 0.014 -10000 0 0 74 74
GPC1/VEGF165 homodimer/VEGFR1 homodimer 0.049 0.023 -10000 0 -0.11 6 6
LYN -0.016 0.025 0.19 5 -0.12 1 6
mol:Spermine -0.01 0.002 -10000 0 -10000 0 0
cell growth 0.055 0.049 -10000 0 -0.11 22 22
BMP signaling pathway -0.039 0.01 0 31 -10000 0 31
SRC -0.018 0.025 0.19 5 -0.12 1 6
TGFBR1 0.039 0.008 -10000 0 0 23 23
mol:Cu2+ 0 0 -10000 0 -10000 0 0
PLA2G2A 0.036 0.014 -10000 0 0 67 67
GPC1 0.039 0.01 -10000 0 0 31 31
TGFBR1 (dimer) 0.039 0.008 -10000 0 0 23 23
VEGFA 0 0 -10000 0 -10000 0 0
BLK -0.015 0.024 0.19 4 -0.12 1 5
HCK -0.017 0.025 0.19 5 -10000 0 5
FGF2 0.039 0.01 -10000 0 0 33 33
FGFR1 0.033 0.017 -10000 0 0 112 112
VEGFR1 homodimer 0.039 0.009 -10000 0 0 28 28
TGFBR2 0.039 0.01 -10000 0 0 34 34
cell death 0.046 0.044 -10000 0 -0.13 27 27
ATIII/GPC1 0.055 0.019 -10000 0 -0.13 1 1
PLA2G2A/GPC1 0.05 0.027 -10000 0 -0.13 3 3
LCK -0.018 0.027 0.19 6 -10000 0 6
neuron differentiation 0.049 0.025 -10000 0 -0.13 1 1
PrPc/Cu2+ 0.02 0.036 -10000 0 -0.12 31 31
APP 0.038 0.011 -10000 0 0 41 41
TGFBR2 (dimer) 0.039 0.01 -10000 0 0 34 34
Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin 0.014 0.078 -10000 0 -0.15 93 93
AKT1 0.018 0.11 0.27 5 -0.31 20 25
PTK2B -0.012 0.078 0.2 13 -0.31 7 20
VEGFR2 homodimer/Frs2 0.033 0.057 -10000 0 -0.37 4 4
CAV1 0.036 0.014 -10000 0 0 75 75
CALM1 0.039 0.009 -10000 0 0 26 26
VEGFR2 homodimer/VEGFA homodimer/Frs2 0.031 0.058 -10000 0 -0.36 4 4
endothelial cell proliferation 0.036 0.098 0.28 15 -0.3 9 24
mol:Ca2+ 0.023 0.068 0.26 3 -0.29 7 10
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac 0.046 0.076 -10000 0 -0.21 20 20
RP11-342D11.1 -0.009 0.052 0.17 13 -0.32 5 18
CDH5 0.036 0.013 -10000 0 0 65 65
VEGFA homodimer 0.06 0.048 -10000 0 -0.11 27 27
SHC1 0.039 0.008 -10000 0 0 23 23
SHC2 0.036 0.014 -10000 0 0 67 67
HRAS/GDP 0.037 0.067 -10000 0 -0.24 10 10
SH2D2A 0.04 0.007 -10000 0 0 17 17
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS 0.055 0.087 0.3 1 -0.37 6 7
VEGFR2 homodimer/VEGFA homodimer/TsAd 0.036 0.055 -10000 0 -0.32 5 5
VEGFR1 homodimer 0.039 0.009 -10000 0 0 28 28
SHC/GRB2/SOS1 0.069 0.083 -10000 0 -0.25 11 11
GRB10 0.024 0.072 0.26 2 -0.35 8 10
PTPN11 0.039 0.009 -10000 0 0 29 29
GRB2 0.04 0.008 -10000 0 0 21 21
PAK1 0.036 0.013 -10000 0 0 65 65
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin 0.051 0.086 -10000 0 -0.21 21 21
HRAS 0.039 0.01 -10000 0 0 31 31
VEGF/Rho/ROCK1/Integrin Complex -0.016 0.11 -10000 0 -0.26 76 76
HIF1A 0.038 0.01 -10000 0 0 37 37
FRS2 0.038 0.011 -10000 0 0 41 41
oxygen and reactive oxygen species metabolic process 0.044 0.075 -10000 0 -0.21 20 20
mol:GTP 0 0 -10000 0 -10000 0 0
FLT4 0.04 0.008 -10000 0 0 22 22
Nck/Pak 0.036 0.056 -10000 0 -0.14 44 44
VEGFR2 homodimer/VEGFA homodimer/Fyn 0.024 0.061 -10000 0 -0.27 7 7
mol:GDP 0.053 0.074 -10000 0 -0.24 11 11
mol:NADP 0.04 0.083 0.28 5 -0.33 7 12
eNOS/Hsp90 0.037 0.078 0.26 5 -0.31 7 12
PIK3R1 0.034 0.016 -10000 0 0 99 99
mol:IP3 0.023 0.069 0.26 3 -0.3 7 10
HIF1A/ARNT 0.046 0.044 -10000 0 -0.14 22 22
SHB 0.04 0.006 -10000 0 0 11 11
VEGFA 0.002 0.004 -10000 0 -0.037 6 6
VEGFC 0.036 0.014 -10000 0 0 69 69
FAK1/Vinculin 0.01 0.12 0.26 3 -0.3 37 40
mol:Ca ++ 0 0 -10000 0 -10000 0 0
RHOA 0.04 0.006 -10000 0 0 13 13
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin 0.023 0.087 -10000 0 -0.21 33 33
PTPN6 0.037 0.013 -10000 0 0 56 56
EPAS1 0.043 0.031 -10000 0 -0.27 3 3
mol:L-citrulline 0.04 0.083 0.28 5 -0.33 7 12
ITGAV 0.033 0.017 -10000 0 0 110 110
PIK3CA 0.029 0.019 -10000 0 0 166 166
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2 0.053 0.068 -10000 0 -0.31 5 5
VEGFR2 homodimer/VEGFA homodimer 0.041 0.061 -10000 0 -0.28 8 8
VEGFR2/3 heterodimer 0.034 0.057 -10000 0 -0.33 5 5
VEGFB 0.038 0.011 -10000 0 0 40 40
MAPK11 -0.003 0.078 0.25 8 -0.32 10 18
VEGFR2 homodimer 0.019 0.044 -10000 0 -0.38 5 5
FLT1 0.039 0.009 -10000 0 0 28 28
NEDD4 0.039 0.016 -10000 0 -0.053 5 5
MAPK3 0.001 0.074 0.24 6 -0.27 8 14
MAPK1 0.001 0.074 0.24 7 -0.3 7 14
VEGFA145/NRP2 0.015 0.045 -10000 0 -0.11 54 54
VEGFR1/2 heterodimer 0.034 0.058 -10000 0 -0.29 7 7
KDR 0.019 0.044 -10000 0 -0.38 5 5
VEGFA165/NRP1/VEGFR2 homodimer 0.03 0.071 -10000 0 -0.21 19 19
SRC 0.039 0.009 -10000 0 0 28 28
platelet activating factor biosynthetic process 0.003 0.079 0.24 8 -0.3 7 15
PI3K 0.013 0.081 -10000 0 -0.31 9 9
VEGFR2 homodimer/VEGFA homodimer/NCK1 0.026 0.062 -10000 0 -0.25 10 10
FES 0.024 0.068 0.26 3 -0.33 5 8
GAB1 0.02 0.083 0.26 2 -0.3 17 19
VEGFR2 homodimer/VEGFA homodimer/Src 0.035 0.053 -10000 0 -0.28 5 5
CTNNB1 0.039 0.01 -10000 0 0 32 32
SOS1 0.037 0.012 -10000 0 0 51 51
ARNT 0.037 0.012 -10000 0 0 50 50
eNOS/Caveolin-1 0.047 0.084 0.31 2 -0.35 6 8
VEGFR2 homodimer/VEGFA homodimer/Yes 0.028 0.062 -10000 0 -0.27 8 8
PI3K/GAB1 0.027 0.11 0.27 3 -0.31 20 23
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak 0.048 0.082 -10000 0 -0.21 13 13
PRKACA 0.035 0.015 -10000 0 0 84 84
VEGFR2/3 heterodimer/VEGFC homodimer 0.051 0.066 -10000 0 -0.29 6 6
HSP90AA1 0 0 -10000 0 -10000 0 0
CDC42 0.024 0.068 0.26 3 -0.33 5 8
actin cytoskeleton reorganization 0.035 0.054 -10000 0 -0.32 5 5
PTK2 -0.007 0.11 0.23 1 -0.32 33 34
EDG1 0.023 0.065 0.24 2 -0.33 5 7
mol:DAG 0.023 0.069 0.26 3 -0.3 7 10
CaM/Ca2+ 0.038 0.069 0.25 3 -0.26 8 11
MAP2K3 -0.006 0.063 0.18 28 -0.33 5 33
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4 0.042 0.07 0.24 5 -0.34 9 14
PLCG1 0.023 0.069 0.26 3 -0.3 7 10
VEGFR2 homodimer/VEGFA homodimer/Src/Shb 0.058 0.062 -10000 0 -0.27 5 5
IQGAP1 0.036 0.013 -10000 0 0 66 66
YES1 0.037 0.012 -10000 0 0 51 51
VEGFR2 homodimer/VEGFA homodimer/SHP2 0.031 0.06 -10000 0 -0.28 7 7
VEGFR2 homodimer/VEGFA homodimer/SHP1 0.034 0.053 -10000 0 -0.31 5 5
cell migration 0 0.13 0.26 4 -0.33 38 42
mol:PI-3-4-5-P3 0.013 0.078 -10000 0 -0.3 9 9
FYN 0.034 0.016 -10000 0 0 94 94
VEGFB/NRP1 0.028 0.064 0.22 2 -0.23 10 12
mol:NO 0.04 0.083 0.28 5 -0.33 7 12
PXN 0.04 0.006 -10000 0 0 10 10
HRAS/GTP 0.016 0.056 -10000 0 -0.23 11 11
VEGFR2 homodimer/VEGFA homodimer/GRB10 0.025 0.061 -10000 0 -0.34 9 9
VHL 0.039 0.008 -10000 0 0 23 23
ITGB3 0.032 0.017 -10000 0 0 116 116
NOS3 0.04 0.088 0.29 4 -0.37 7 11
VEGFR2 homodimer/VEGFA homodimer/Sck 0.031 0.055 -10000 0 -0.31 5 5
RAC1 0.039 0.009 -10000 0 0 28 28
PRKCA -0.006 0.067 0.18 35 -0.33 5 40
PRKCB -0.002 0.066 0.18 37 -0.33 5 42
VCL 0.039 0.01 -10000 0 0 34 34
VEGFA165/NRP1 0.006 0.048 0.17 5 -0.26 8 13
VEGFR1/2 heterodimer/VEGFA homodimer 0.034 0.057 -10000 0 -0.28 7 7
VEGFA165/NRP2 0.015 0.045 -10000 0 -0.11 54 54
MAPKKK cascade -0.02 0.07 0.18 24 -0.34 7 31
NRP2 0.034 0.015 -10000 0 0 93 93
VEGFC homodimer 0.036 0.014 -10000 0 0 69 69
NCK1 0.036 0.014 -10000 0 0 70 70
ROCK1 0.04 0.008 -10000 0 0 21 21
FAK1/Paxillin 0.012 0.12 0.26 3 -0.31 33 36
MAP3K13 0.017 0.065 0.26 3 -0.29 7 10
PDPK1 0.001 0.068 0.24 1 -0.28 7 8
LPA4-mediated signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
ADCY4 -0.015 0.005 -10000 0 -10000 0 0
ADCY5 -0.014 0.006 -10000 0 -10000 0 0
ADCY6 -0.015 0.004 -10000 0 -10000 0 0
ADCY7 -0.014 0.005 0 68 -10000 0 68
ADCY1 -0.015 0.004 0 39 -10000 0 39
ADCY2 -0.014 0.006 -10000 0 -10000 0 0
ADCY3 -0.015 0.004 0 44 -10000 0 44
ADCY8 -0.009 0.008 -10000 0 -10000 0 0
PRKCE -0.01 0.002 0 28 -10000 0 28
ADCY9 -0.014 0.006 0 71 -10000 0 71
mol:DAG 0 0 -10000 0 -10000 0 0
cAMP biosynthetic process 0.045 0.078 0.2 52 -0.2 5 57
IL27-mediated signaling events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
TGFB1 0.036 0.014 -10000 0 0 69 69
CD4-positive alpha-beta T cell lineage commitment 0 0 -10000 0 -10000 0 0
cytokine production during immune response -0.001 0.11 0.44 13 -10000 0 13
IL27/IL27R/JAK1 0.08 0.11 -10000 0 -0.88 2 2
TBX21 0.006 0.1 0.38 4 -0.56 2 6
IL12B 0.041 0.008 -10000 0 0 18 18
IL12A -0.006 0.006 0.012 26 -10000 0 26
IL6ST 0.036 0.017 -10000 0 -0.032 2 2
IL27RA/JAK1 0.05 0.098 -10000 0 -1 2 2
IL27 0.043 0.009 -10000 0 -0.032 2 2
TYK2 0.038 0.015 -10000 0 -0.033 2 2
T-helper cell lineage commitment 0.005 0.059 0.2 17 -0.18 29 46
T-helper 2 cell differentiation -0.001 0.11 0.44 13 -10000 0 13
T cell proliferation during immune response -0.001 0.11 0.44 13 -10000 0 13
MAPKKK cascade 0.001 0.11 -10000 0 -0.44 13 13
STAT3 0.038 0.011 -10000 0 0 41 41
STAT2 0.038 0.012 -10000 0 0 49 49
STAT1 0.034 0.016 -10000 0 0 102 102
IL12RB1 0.038 0.012 -10000 0 0 50 50
positive regulation of tyrosine phosphorylation of STAT protein 0 0 -10000 0 -10000 0 0
IL12RB2 0.002 0.1 0.4 1 -0.52 2 3
IL27/IL27R/JAK2/TYK2 0.001 0.11 -10000 0 -0.44 13 13
positive regulation of T cell mediated cytotoxicity 0.001 0.11 -10000 0 -0.44 13 13
STAT1 (dimer) 0.062 0.12 -10000 0 -0.78 2 2
JAK2 0.035 0.018 -10000 0 -10000 0 0
JAK1 0.039 0.01 -10000 0 0 33 33
STAT2 (dimer) 0.019 0.13 -10000 0 -0.42 15 15
T cell proliferation 0.002 0.11 0.34 1 -0.42 13 14
IL12/IL12R/TYK2/JAK2 0.009 0.17 -10000 0 -0.72 25 25
IL17A 0.006 0.055 0.2 17 -0.18 26 43
mast cell activation -0.001 0.11 0.44 13 -10000 0 13
IFNG 0.013 0.031 0.11 1 -0.092 9 10
T cell differentiation -0.001 0.003 0.014 2 -0.016 5 7
STAT3 (dimer) 0.024 0.13 -10000 0 -0.42 14 14
STAT5A (dimer) 0.025 0.13 -10000 0 -0.43 13 13
STAT4 (dimer) 0.025 0.13 -10000 0 -0.42 13 13
STAT4 0.039 0.008 -10000 0 0 24 24
T cell activation -0.008 0.01 -10000 0 -0.045 29 29
IL27R/JAK2/TYK2 0.048 0.096 -10000 0 -0.93 2 2
GATA3 0.015 0.12 0.64 17 -10000 0 17
IL18 -0.006 0.006 0.002 179 -10000 0 179
positive regulation of mast cell cytokine production 0.024 0.13 -10000 0 -0.41 14 14
IL27/EBI3 0.058 0.022 -10000 0 -10000 0 0
IL27RA 0.022 0.1 -10000 0 -1.1 2 2
IL6 0.034 0.016 -10000 0 0 100 100
STAT5A 0.038 0.01 -10000 0 0 36 36
monocyte differentiation 0 0 -10000 0 -10000 0 0
IL2 -0.009 0.034 0.49 2 -10000 0 2
IL1B -0.007 0.006 0.002 145 -10000 0 145
EBI3 0.039 0.014 -10000 0 -10000 0 0
TNF -0.008 0.005 0.006 60 -10000 0 60
Alternative NF-kappaB pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
IKK alpha homodimer 0.047 0.044 -9999 0 -0.13 27 27
FBXW11 0.04 0.008 -9999 0 0 22 22
proteasomal ubiquitin-dependent protein catabolic process 0 0 -9999 0 -10000 0 0
beta TrCP1/SCF ubiquitin ligase complex 0.039 0.008 -9999 0 0 22 22
CHUK 0.038 0.011 -9999 0 0 46 46
NF kappa B2 p100/RelB 0.093 0.066 -9999 0 -0.11 32 32
NFKB1 0.036 0.013 -9999 0 0 66 66
MAP3K14 0.04 0.008 -9999 0 0 20 20
NF kappa B1 p50/RelB 0.043 0.048 -9999 0 -0.13 33 33
RELB 0.039 0.01 -9999 0 0 33 33
NFKB2 0.04 0.007 -9999 0 0 18 18
NF kappa B2 p52/RelB 0.05 0.023 -9999 0 -0.13 5 5
regulation of B cell activation 0.049 0.022 -9999 0 -0.13 5 5
Signaling events mediated by HDAC Class II

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
G beta1gamma2/HDAC5 0.088 0.048 -10000 0 -0.12 17 17
HDAC3 0.04 0.006 -10000 0 0 10 10
Ran/GTP/Exportin 1/HDAC4 -0.026 0.024 -10000 0 -0.11 32 32
GATA1/HDAC4 0.058 0.013 -10000 0 -10000 0 0
GATA1/HDAC5 0.059 0.012 -10000 0 -10000 0 0
GATA2/HDAC5 0.055 0.018 -10000 0 -10000 0 0
HDAC5/BCL6/BCoR 0.053 0.056 -10000 0 -0.12 33 33
HDAC9 0.036 0.014 -10000 0 0 74 74
Glucocorticoid receptor/Hsp90/HDAC6 0.044 0.038 -10000 0 -0.11 29 29
HDAC4/ANKRA2 0.049 0.031 -10000 0 -0.13 8 8
HDAC5/YWHAB 0.052 0.027 -10000 0 -0.13 6 6
NPC/RanGAP1/SUMO1/Ubc9 0.009 0.034 -10000 0 -0.14 25 25
GATA2 0.039 0.01 -10000 0 0 31 31
HDAC4/RFXANK 0.046 0.039 -10000 0 -0.13 18 18
BCOR 0.041 0.005 -10000 0 0 8 8
mol:GTP 0 0 -10000 0 -10000 0 0
HDAC10 0.029 0.019 -10000 0 0 157 157
HDAC5 0.04 0.008 -10000 0 0 21 21
GNB1/GNG2 0.05 0.036 -10000 0 -0.13 16 16
Histones -0.01 0.07 -10000 0 -0.19 37 37
ADRBK1 0.041 0.004 -10000 0 0 6 6
HDAC4 0.039 0.009 -10000 0 0 25 25
XPO1 0.039 0.01 -10000 0 0 35 35
HDAC5/ANKRA2 0.049 0.031 -10000 0 -0.13 8 8
HDAC4/Ubc9 0.055 0.019 -10000 0 -0.13 1 1
HDAC7 0 0 -10000 0 -10000 0 0
HDAC5/14-3-3 E 0.052 0.029 -10000 0 -0.13 7 7
TUBA1B 0 0 -10000 0 -10000 0 0
HDAC6 0.04 0.007 -10000 0 0 14 14
HDAC5/RFXANK 0.046 0.04 -10000 0 -0.13 20 20
CAMK4 0.037 0.012 -10000 0 0 55 55
Tubulin/HDAC6 0.051 0.016 -10000 0 -10000 0 0
SUMO1 0.04 0.007 -10000 0 0 14 14
EntrezGene:9972 0 0 -10000 0 -10000 0 0
YWHAB 0.038 0.011 -10000 0 0 45 45
GATA1 0.041 0.002 -10000 0 0 1 1
EntrezGene:8021 0 0 -10000 0 -10000 0 0
YWHAE 0.037 0.013 -10000 0 0 58 58
NR3C1 0.038 0.011 -10000 0 0 42 42
SUMO1/HDAC4 0.037 0.063 -10000 0 -0.18 17 17
SRF 0.038 0.01 -10000 0 0 37 37
HDAC4/YWHAB 0.052 0.027 -10000 0 -0.13 6 6
Tubulin 0.029 0.007 -10000 0 -10000 0 0
HDAC4/14-3-3 E 0.051 0.029 -10000 0 -0.13 7 7
GNB1 0.039 0.01 -10000 0 0 33 33
RANGAP1 0.037 0.012 -10000 0 0 54 54
BCL6/BCoR 0.038 0.051 -10000 0 -0.14 33 33
HDAC4/HDAC3/SMRT (N-CoR2) 0.073 0.032 -10000 0 -0.12 5 5
HDAC4/SRF 0.067 0.035 -10000 0 -0.12 2 2
HDAC4/ER alpha 0.038 0.053 -10000 0 -0.13 41 41
EntrezGene:23225 0 0 -10000 0 -10000 0 0
positive regulation of chromatin silencing -0.01 0.07 -10000 0 -0.19 37 37
cell motility 0.05 0.015 -10000 0 -10000 0 0
EntrezGene:23636 0 0 -10000 0 -10000 0 0
UBE2I 0.039 0.009 -10000 0 0 27 27
HDAC7/HDAC3 0.029 0.01 -10000 0 -0.12 2 2
BCL6 0.031 0.018 -10000 0 0 130 130
HDAC4/CaMK II delta B 0.039 0.009 -10000 0 0 25 25
Hsp90/HDAC6 0.03 0.005 -10000 0 -10000 0 0
ESR1 0.034 0.015 -10000 0 0 91 91
HDAC6/HDAC11 0.056 0.025 -10000 0 -0.13 7 7
Ran/GTP/Exportin 1 0.035 0.071 -10000 0 -0.18 36 36
NPC 0.019 0.022 -10000 0 -0.083 23 23
MEF2C 0.037 0.013 -10000 0 0 61 61
RAN 0.04 0.008 -10000 0 0 21 21
HDAC4/MEF2C 0.092 0.061 -10000 0 -0.11 16 16
GNG2 0.039 0.009 -10000 0 0 29 29
NCOR2 0.039 0.01 -10000 0 0 31 31
TUBB2A 0.039 0.01 -10000 0 0 33 33
HDAC11 0.04 0.008 -10000 0 0 21 21
HSP90AA1 0 0 -10000 0 -10000 0 0
RANBP2 0.039 0.009 -10000 0 0 30 30
ANKRA2 0.036 0.014 -10000 0 0 72 72
RFXANK 0.036 0.014 -10000 0 0 74 74
nuclear import -0.036 0.039 0.18 12 -10000 0 12
Signaling events mediated by HDAC Class III

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
EP300 0.036 0.014 -10000 0 0 69 69
HDAC4 0.039 0.009 -10000 0 0 25 25
induction of apoptosis 0 0 -10000 0 -10000 0 0
regulation of S phase of mitotic cell cycle 0.013 0.004 -10000 0 -10000 0 0
CDKN1A 0.016 0.051 0.37 4 -10000 0 4
KAT2B 0 0 -10000 0 -10000 0 0
BAX 0.039 0.008 -10000 0 0 23 23
FOXO3 0.002 0.04 0.25 14 -10000 0 14
FOXO1 0 0 -10000 0 -10000 0 0
FOXO4 0.005 0.033 -10000 0 -0.18 17 17
response to UV 0 0 -10000 0 -10000 0 0
XRCC6 0.036 0.014 -10000 0 0 69 69
TAT 0.036 0.013 -10000 0 0 65 65
mol:Lysophosphatidic acid 0 0 -10000 0 -10000 0 0
MYOD1 -0.01 0.002 -10000 0 -10000 0 0
PPARGC1A 0.037 0.012 -10000 0 0 52 52
FHL2 0.04 0.008 -10000 0 0 19 19
response to nutrient levels 0 0 -10000 0 -10000 0 0
KU70/SIRT1 0.045 0.042 -10000 0 -0.17 16 16
HIST2H4A -0.013 0.004 -10000 0 -10000 0 0
SIRT1/FOXO3a 0.038 0.044 0.15 57 -0.2 2 59
SIRT1 0.037 0.007 -10000 0 -10000 0 0
response to hypoxia 0 0 -10000 0 -10000 0 0
SIRT1/MEF2D/HDAC4 0.071 0.033 -10000 0 -0.12 8 8
SIRT1/Histone H1b 0.002 0.09 -10000 0 -0.2 70 70
apoptosis -0.062 0.046 0.14 16 -10000 0 16
SIRT1/PGC1A 0.045 0.025 -10000 0 -0.11 8 8
p53/SIRT1 -0.008 0.087 -10000 0 -0.14 152 152
SIRT1/FOXO4 0.007 0.076 -10000 0 -0.15 86 86
FOXO1/FHL2/SIRT1 0.045 0.024 -10000 0 -0.1 12 12
HIST1H1E -0.004 0.068 -10000 0 -0.2 51 51
SIRT1/p300 0.044 0.041 -10000 0 -0.14 22 22
muscle cell differentiation -0.018 0.023 0.11 9 -0.21 2 11
TP53 0.023 0.018 -10000 0 -10000 0 0
KU70/SIRT1/BAX 0.063 0.046 -10000 0 -0.15 16 16
CREBBP 0.037 0.012 -10000 0 0 53 53
MEF2D 0.04 0.007 -10000 0 0 18 18
HIV-1 Tat/SIRT1 0.048 0.029 -10000 0 -0.13 8 8
ACSS2 -0.021 0.009 0.04 1 -10000 0 1
SIRT1/PCAF/MYOD 0.018 0.023 0.21 2 -0.11 9 11
VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer 0.035 0.052 -10000 0 -0.4 5 5
VEGFR1 homodimer/NRP1 0.009 0.046 -10000 0 -0.39 5 5
mol:DAG -0.024 0.039 0.19 1 -0.3 6 7
VEGFR1 homodimer/NRP1/VEGFR 121 0.008 0.042 -10000 0 -0.36 5 5
CaM/Ca2+ 0.026 0.05 -10000 0 -0.28 7 7
HIF1A 0.045 0.033 -10000 0 -0.27 5 5
GAB1 0.037 0.013 -10000 0 0 58 58
AKT1 0.01 0.094 0.23 15 -0.27 16 31
PLCG1 -0.024 0.039 0.19 1 -0.31 6 7
NOS3 0.025 0.071 0.32 3 -0.26 10 13
CBL 0.04 0.008 -10000 0 0 20 20
mol:NO 0.029 0.076 0.3 7 -0.26 10 17
FLT1 0.018 0.044 -10000 0 -0.49 4 4
PGF 0.039 0.008 -10000 0 0 23 23
VEGFR1 homodimer/NRP2/VEGFR121 0.018 0.061 -10000 0 -0.3 8 8
CALM1 0.039 0.009 -10000 0 0 26 26
PIK3CA 0.029 0.019 -10000 0 0 166 166
eNOS/Hsp90 0.02 0.067 0.22 2 -0.25 9 11
endothelial cell proliferation -0.003 0.062 0.29 2 -0.3 10 12
mol:Ca2+ -0.024 0.039 0.19 1 -0.3 6 7
MAPK3 -0.03 0.049 0.2 4 -0.25 9 13
MAPK1 -0.028 0.048 0.2 4 -0.25 8 12
PIK3R1 0.034 0.016 -10000 0 0 99 99
PLGF homodimer 0.039 0.008 -10000 0 0 23 23
PRKACA 0.035 0.015 -10000 0 0 84 84
RP11-342D11.1 0 0 -10000 0 -10000 0 0
CAV1 0.036 0.014 -10000 0 0 75 75
VEGFA homodimer 0 0 -10000 0 -10000 0 0
VEGFR1 homodimer/VEGFA homodimer 0.009 0.046 -10000 0 -0.39 5 5
platelet activating factor biosynthetic process -0.027 0.056 0.32 1 -0.28 6 7
PI3K 0.037 0.077 -10000 0 -0.24 15 15
PRKCA -0.02 0.046 0.22 4 -0.26 8 12
PRKCB -0.022 0.036 0.18 1 -0.28 6 7
VEGFR1 homodimer/PLGF homodimer 0.035 0.053 -10000 0 -0.4 5 5
VEGFA 0 0 -10000 0 -10000 0 0
VEGFB 0.038 0.011 -10000 0 0 40 40
mol:IP3 -0.024 0.039 0.19 1 -0.3 6 7
RASA1 -0.021 0.045 0.19 2 -0.32 7 9
NRP2 0.034 0.015 -10000 0 0 93 93
VEGFR1 homodimer 0.018 0.044 -10000 0 -0.49 4 4
VEGFB homodimer 0.038 0.011 -10000 0 0 40 40
NCK1 0.036 0.014 -10000 0 0 70 70
eNOS/Caveolin-1 0.045 0.083 0.32 6 -0.26 10 16
PTPN11 0.039 0.009 -10000 0 0 29 29
mol:PI-3-4-5-P3 0.036 0.076 -10000 0 -0.23 16 16
mol:L-citrulline 0.029 0.076 0.3 7 -0.26 10 17
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP 0.041 0.065 -10000 0 -0.27 9 9
VEGFR1 homodimer/VEGFA homodimer/NCK1 0.023 0.058 -10000 0 -0.28 10 10
CD2AP 0.037 0.013 -10000 0 0 62 62
PI3K/GAB1 0.042 0.085 -10000 0 -0.24 16 16
PDPK1 0.007 0.094 0.18 93 -0.3 7 100
VEGFR1 homodimer/VEGFA homodimer/SHP2 0.028 0.054 -10000 0 -0.28 9 9
mol:NADP 0.029 0.076 0.3 7 -0.26 10 17
HSP90AA1 0 0 -10000 0 -10000 0 0
ubiquitin-dependent protein catabolic process 0.039 0.063 -10000 0 -0.27 9 9
VEGFR1 homodimer/NRP2 0.028 0.057 -10000 0 -0.34 8 8
Angiopoietin receptor Tie2-mediated signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
AKT1 0.014 0.17 -10000 0 -0.69 14 14
NCK1/PAK1/Dok-R -0.031 0.073 -10000 0 -0.33 14 14
NCK1/Dok-R 0.051 0.097 -10000 0 -0.87 2 2
PIK3CA 0.028 0.019 -10000 0 0 166 166
mol:beta2-estradiol -0.008 0.008 -10000 0 -10000 0 0
RELA 0.04 0.006 -10000 0 0 10 10
SHC1 0.04 0.009 -10000 0 0 23 23
Rac/GDP 0.029 0.009 -10000 0 -0.12 1 1
F2 0.011 0.037 -10000 0 -0.082 1 1
TNIP2 0.038 0.011 -10000 0 0 43 43
NF kappa B/RelA 0.075 0.1 -10000 0 -0.83 2 2
FN1 0.021 0.021 -10000 0 0 268 268
PLD2 0.032 0.079 -10000 0 -0.89 2 2
PTPN11 0.039 0.009 -10000 0 0 29 29
GRB14 0.038 0.012 -10000 0 0 49 49
ELK1 0.033 0.081 -10000 0 -0.84 2 2
GRB7 0.037 0.013 -10000 0 0 57 57
PAK1 0.036 0.013 -10000 0 0 65 65
Tie2/Ang1/alpha5/beta1 Integrin 0.023 0.11 -10000 0 -0.86 2 2
CDKN1A 0.012 0.19 -10000 0 -0.62 38 38
ITGA5 0.036 0.013 -10000 0 0 64 64
mol:GTP 0 0 -10000 0 -10000 0 0
RasGAP/Dok-R 0.056 0.096 -10000 0 -0.87 2 2
CRK 0.038 0.012 -10000 0 0 49 49
mol:NO 0.023 0.15 -10000 0 -0.52 15 15
PLG 0.031 0.077 -10000 0 -0.89 2 2
mol:GDP 0 0 -10000 0 -10000 0 0
chemokinesis 0.027 0.14 -10000 0 -0.75 6 6
GRB2 0.04 0.008 -10000 0 0 21 21
PIK3R1 0.034 0.016 -10000 0 0 99 99
ANGPT2 -0.045 0.28 -10000 0 -1 37 37
BMX 0.031 0.078 -10000 0 -0.89 2 2
ANGPT1 0.013 0.047 -10000 0 -10000 0 0
tube development -0.002 0.21 -10000 0 -0.7 38 38
ANGPT4 0.035 0.02 -10000 0 -0.014 71 71
response to hypoxia 0.001 0.008 0.033 1 -0.062 2 3
Tie2/Ang1/GRB14 0.051 0.089 -10000 0 -0.91 2 2
alpha5/beta1 Integrin 0.043 0.046 -10000 0 -0.13 29 29
FGF2 0.039 0.011 -10000 0 0 33 33
STAT5A (dimer) 0.015 0.24 -10000 0 -0.8 38 38
mol:L-citrulline 0.023 0.15 -10000 0 -0.52 15 15
AGTR1 0.032 0.025 -10000 0 -0.018 93 93
MAPK14 0.041 0.13 -10000 0 -1 4 4
Tie2/SHP2 0.039 0.11 -10000 0 -0.76 3 3
TEK 0.028 0.1 -10000 0 -0.8 3 3
RPS6KB1 0.014 0.16 -10000 0 -0.65 12 12
Angiotensin II/AT1 0.025 0.024 -10000 0 -0.059 33 33
Tie2/Ang1/GRB2 0.056 0.091 -10000 0 -0.91 2 2
MAPK3 0.026 0.076 -10000 0 -0.84 2 2
MAPK1 0.028 0.079 -10000 0 -0.84 2 2
Tie2/Ang1/GRB7 0.053 0.089 -10000 0 -0.91 2 2
NFKB1 0.036 0.013 -10000 0 0 66 66
MAPK8 0.031 0.081 -10000 0 -0.89 2 2
PI3K 0.011 0.16 -10000 0 -0.93 6 6
FES 0.043 0.11 -10000 0 -1 2 2
Crk/Dok-R 0.058 0.094 -10000 0 -0.87 2 2
Tie2/Ang1/ABIN2 0.054 0.09 -10000 0 -0.91 2 2
blood circulation 0 0 -10000 0 -10000 0 0
negative regulation of caspase activity 0.018 0.16 -10000 0 -0.61 15 15
STAT5A 0.039 0.01 -10000 0 0 36 36
mol:ROS 0 0 -10000 0 -10000 0 0
PTK2 0.054 0.18 -10000 0 -0.63 9 9
Tie2/Ang2 -0.012 0.27 -10000 0 -0.95 38 38
Tie2/Ang1 0.039 0.081 -10000 0 -0.94 2 2
FOXO1 0.012 0.18 -10000 0 -0.61 37 37
ELF1 0.047 0.018 -10000 0 -0.13 2 2
ELF2 0.036 0.079 -10000 0 -0.89 2 2
mol:Choline 0.032 0.077 -10000 0 -0.87 2 2
cell migration -0.017 0.047 -10000 0 -0.19 13 13
FYN -0.01 0.23 -10000 0 -0.8 38 38
DOK2 0.032 0.017 -10000 0 0 118 118
negative regulation of cell cycle 0.015 0.17 -10000 0 -0.56 38 38
ETS1 0.041 0.021 -10000 0 -10000 0 0
PXN 0.053 0.16 0.39 2 -0.55 9 11
ITGB1 0.038 0.01 -10000 0 0 36 36
NOS3 0.02 0.16 -10000 0 -0.59 14 14
RAC1 0.039 0.009 -10000 0 0 28 28
TNF 0.048 0.013 -10000 0 -10000 0 0
MAPKKK cascade 0.032 0.077 -10000 0 -0.87 2 2
RASA1 0.037 0.013 -10000 0 0 56 56
Tie2/Ang1/Shc 0.058 0.091 -10000 0 -0.91 2 2
NCK1 0.036 0.014 -10000 0 0 70 70
vasculogenesis 0.025 0.14 -10000 0 -0.47 15 15
mol:Phosphatidic acid 0.032 0.077 -10000 0 -0.87 2 2
mol:Angiotensin II 0 0.008 -10000 0 -0.033 30 30
mol:NADP 0.023 0.15 -10000 0 -0.52 15 15
Rac1/GTP 0.028 0.15 -10000 0 -0.65 9 9
MMP2 0.032 0.088 -10000 0 -0.89 2 2
Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
HDAC1 0.038 0.012 -10000 0 0 49 49
Ran/GTP/Exportin 1/HDAC4 -0.028 0.033 -10000 0 -0.14 33 33
MDM2/SUMO1 0.036 0.063 -10000 0 -0.18 19 19
HDAC4 0.039 0.009 -10000 0 0 25 25
Ran/GTP/Exportin 1/HDAC1 -0.031 0.039 -10000 0 -0.14 46 46
SUMO1 0.04 0.007 -10000 0 0 14 14
NPC/RanGAP1/SUMO1 0.007 0.033 -10000 0 -0.14 25 25
mol:GTP 0 0 -10000 0 -10000 0 0
XPO1 -0.001 0.031 -10000 0 -0.14 12 12
EntrezGene:23636 0 0 -10000 0 -10000 0 0
RAN 0.04 0.008 -10000 0 0 21 21
EntrezGene:8021 0 0 -10000 0 -10000 0 0
RANBP2 0.039 0.009 -10000 0 0 30 30
SUMO1/HDAC4 0.037 0.063 -10000 0 -0.18 17 17
SUMO1/HDAC1 0.034 0.066 -10000 0 -0.18 25 25
RANGAP1 0.037 0.012 -10000 0 0 54 54
MDM2/SUMO1/SUMO1 0.083 0.053 -10000 0 -0.12 17 17
NPC/RanGAP1/SUMO1/RanBP2/Ubc9 0.009 0.034 -10000 0 -0.14 25 25
Ran/GTP 0.02 0.057 -10000 0 -0.15 35 35
EntrezGene:23225 0 0 -10000 0 -10000 0 0
MDM2 0.038 0.01 -10000 0 0 36 36
UBE2I 0.039 0.009 -10000 0 0 27 27
Ran/GTP/Exportin 1 0.015 0.066 0.2 8 -0.18 36 44
NPC 0.019 0.022 -10000 0 -0.083 23 23
PIAS2 0.038 0.011 -10000 0 0 42 42
PIAS1 0.039 0.008 -10000 0 0 24 24
EntrezGene:9972 0 0 -10000 0 -10000 0 0
Aurora C signaling

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
INCENP 0.041 0.004 -9999 0 0 6 6
Aurora C/Aurora B/INCENP 0.06 0.045 -9999 0 -0.1 26 26
metaphase 0 0 -9999 0 -10000 0 0
mitosis 0 0 -9999 0 -10000 0 0
H3F3B 0.003 0.068 -9999 0 -0.38 16 16
AURKB 0.035 0.014 -9999 0 0 78 78
AURKC 0.039 0.01 -9999 0 0 34 34
Signaling mediated by p38-alpha and p38-beta

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
PTGS2 0.007 0.11 -10000 0 -0.81 9 9
MKNK1 0.04 0.007 -10000 0 0 15 15
MAPK14 0.041 0.052 0.17 1 -0.13 32 33
ATF2/c-Jun -0.026 0.1 -10000 0 -0.31 44 44
MAPK11 0.029 0.051 -10000 0 -0.13 29 29
MITF 0.018 0.06 -10000 0 -0.29 14 14
MAPKAPK5 0.018 0.057 -10000 0 -0.26 16 16
KRT8 0.014 0.061 -10000 0 -0.22 25 25
MAPKAPK3 0.04 0.006 -10000 0 0 11 11
MAPKAPK2 0.04 0.007 -10000 0 0 14 14
p38alpha-beta/CK2 0.04 0.075 -10000 0 -0.28 14 14
CEBPB 0.02 0.053 -10000 0 -0.29 10 10
SLC9A1 0.019 0.054 -10000 0 -0.28 13 13
mol:GDP 0 0 -10000 0 -10000 0 0
ATF2 0.012 0.074 0.23 1 -0.24 28 29
p38alpha-beta/MNK1 0.051 0.075 -10000 0 -0.3 9 9
JUN -0.028 0.1 -10000 0 -0.31 44 44
PPARGC1A 0.02 0.054 -10000 0 -0.28 12 12
USF1 0.018 0.056 -10000 0 -0.26 15 15
RAB5/GDP/GDI1 -0.001 0.078 -10000 0 -0.19 30 30
NOS2 0.014 0.051 -10000 0 -0.28 12 12
DDIT3 0.015 0.059 -10000 0 -0.22 23 23
RAB5A 0.04 0.006 -10000 0 0 13 13
HSPB1 0.002 0.05 0.3 2 -0.23 15 17
p38alpha-beta/HBP1 0.042 0.081 -10000 0 -0.26 13 13
CREB1 -0.012 0.1 -10000 0 -0.2 107 107
RAB5/GDP 0.029 0.012 -10000 0 -0.12 3 3
EIF4E -0.01 0.056 0.2 11 -0.29 8 19
RPS6KA4 0.019 0.055 -10000 0 -0.27 13 13
PLA2G4A -0.01 0.054 0.24 5 -0.32 9 14
GDI1 0.016 0.06 -10000 0 -0.25 20 20
TP53 0.002 0.058 -10000 0 -0.35 10 10
RPS6KA5 0.017 0.058 -10000 0 -0.25 18 18
ESR1 0.007 0.072 -10000 0 -0.23 38 38
HBP1 0.038 0.011 -10000 0 0 43 43
MEF2C 0.014 0.067 -10000 0 -0.28 19 19
MEF2A 0.017 0.057 -10000 0 -0.26 16 16
EIF4EBP1 -0.008 0.094 -10000 0 -0.2 94 94
KRT19 0.008 0.076 -10000 0 -0.23 39 39
ELK4 0.018 0.055 -10000 0 -0.27 14 14
ATF6 0.018 0.055 -10000 0 -0.25 15 15
ATF1 -0.011 0.098 -10000 0 -0.3 18 18
p38alpha-beta/MAPKAPK2 0.051 0.075 -10000 0 -0.26 11 11
p38alpha-beta/MAPKAPK3 0.052 0.074 -10000 0 -0.29 9 9
Effects of Botulinum toxin

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
STX1A -0.01 0.001 0 11 -10000 0 11
UniProt:P19321 0 0 -10000 0 -10000 0 0
RIMS1/UNC13B 0.056 0.02 -10000 0 -0.13 2 2
STXBP1 0.038 0.011 -10000 0 0 42 42
ACh/CHRNA1 0.027 0.025 0.091 1 -0.048 39 40
RAB3GAP2/RIMS1/UNC13B 0.069 0.041 -10000 0 -0.12 15 15
mol:Ca2+ 0 0 -10000 0 -10000 0 0
UniProt:P30996 0 0 -10000 0 -10000 0 0
UniProt:Q60393 0 0 -10000 0 -10000 0 0
CST086 0 0 -10000 0 -10000 0 0
RIMS1 0.039 0.009 -10000 0 0 29 29
mol:ACh 0.002 0.023 0.072 24 -0.085 4 28
RAB3GAP2 0.039 0.01 -10000 0 0 35 35
STX1A/SNAP25/VAMP2 0.053 0.057 0.18 1 -0.1 24 25
UniProt:P10844 0 0 -10000 0 -10000 0 0
muscle contraction 0.027 0.025 0.091 1 -0.048 39 40
UNC13B 0.04 0.007 -10000 0 0 15 15
CHRNA1 0.037 0.013 -10000 0 0 57 57
UniProt:P10845 0 0 -10000 0 -10000 0 0
ACh/Synaptotagmin 1 0.028 0.025 0.091 1 -0.048 39 40
SNAP25 0.006 0.002 -10000 0 0 58 58
VAMP2 0.005 0.002 -10000 0 0 69 69
SYT1 0.038 0.011 -10000 0 0 42 42
UniProt:Q00496 0 0 -10000 0 -10000 0 0
STXIA/STXBP1 0.033 0.011 -10000 0 -10000 0 0
STX1A/SNAP25 fragment 1/VAMP2 0.053 0.057 0.18 1 -0.1 24 25
Calcium signaling in the CD4+ TCR pathway

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
NFATC1 0.019 0.02 0.076 5 -0.092 3 8
NFATC2 0.019 0.02 0.084 1 -0.11 3 4
NFATC3 0.02 0.02 0.077 6 -0.082 4 10
CD40LG 0.03 0.1 0.3 20 -0.24 1 21
PTGS2 0.011 0.093 0.33 12 -0.26 6 18
JUNB 0.029 0.019 -10000 0 0 159 159
CaM/Ca2+/Calcineurin A alpha-beta B1 0.032 0.016 -10000 0 -0.12 3 3
CaM/Ca2+ 0.032 0.016 -10000 0 -0.12 3 3
CALM1 0.041 0.011 -10000 0 -0.002 28 28
JUN 0.038 0.016 0.1 1 -0.035 1 2
mol:Ca2+ 0.001 0.003 -10000 0 -10000 0 0
Calcineurin A alpha-beta B1/FKBP12/FK506 0.027 0.011 0.067 1 -0.1 2 3
FOSL1 0.04 0.007 -10000 0 0 18 18
CREM 0.039 0.007 -10000 0 0 19 19
Jun/NFAT1-c-4/p21SNFT 0.054 0.066 0.22 3 -10000 0 3
FOS 0.028 0.022 0.1 1 0 201 202
IFNG 0.02 0.094 0.31 11 -0.24 1 12
AP-1/NFAT1-c-4 0.082 0.11 -10000 0 -0.23 3 3
FASLG 0.027 0.1 0.31 16 -0.24 2 18
NFAT1-c-4/ICER1 0.054 0.056 0.21 7 -10000 0 7
IL2RA 0.027 0.1 0.33 17 -0.24 2 19
FKBP12/FK506 0.028 0.012 -10000 0 -0.12 2 2
CSF2 0.029 0.1 0.3 19 -0.24 1 20
JunB/Fra1/NFAT1-c-4 0.046 0.072 0.23 3 -0.18 3 6
IL4 0.029 0.1 0.3 18 -0.24 1 19
IL2 -0.024 0.2 -10000 0 -0.87 30 30
IL3 0.027 0.12 -10000 0 -0.6 19 19
FKBP1A 0.038 0.011 -10000 0 0 44 44
BATF3 0 0 -10000 0 -10000 0 0
mol:FK506 0 0 -10000 0 -10000 0 0
POU2F1 0.045 0.008 -10000 0 -10000 0 0
Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3 0.046 0.01 -10000 0 -0.051 3 3
NFATC2 0.046 0.18 0.41 5 -0.38 38 43
NFATC3 0.071 0.066 0.29 26 -0.24 3 29
CD40LG 0.083 0.15 0.5 4 -0.69 2 6
ITCH 0.022 0.053 0.2 5 -0.2 21 26
CBLB 0.019 0.061 0.2 6 -0.26 20 26
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment 0.043 0.14 0.37 1 -0.5 5 6
JUNB 0.029 0.019 -10000 0 0 159 159
CaM/Ca2+/Calcineurin A alpha-beta B1 0.044 0.048 -10000 0 -0.18 22 22
T cell anergy 0.002 0.066 0.25 5 -0.28 17 22
TLE4 0.007 0.15 0.28 3 -0.41 44 47
Jun/NFAT1-c-4/p21SNFT 0.085 0.15 -10000 0 -0.7 2 2
AP-1/NFAT1-c-4 0.09 0.19 -10000 0 -0.76 2 2
IKZF1 0.021 0.11 0.22 17 -0.25 38 55
T-helper 2 cell differentiation 0.034 0.14 0.45 1 -0.49 1 2
AP-1/NFAT1 0.035 0.14 0.33 2 -0.25 39 41
CALM1 0.042 0.034 -10000 0 -0.11 23 23
EGR2 0.061 0.16 0.58 6 -1.1 2 8
EGR3 0.055 0.13 0.58 5 -0.52 1 6
NFAT1/FOXP3 0.057 0.14 0.32 3 -0.27 35 38
EGR1 0.027 0.021 0.074 1 0 190 191
JUN 0.04 0.026 0.14 2 -0.054 4 6
EGR4 0.041 0.009 -10000 0 -0.035 2 2
mol:Ca2+ 0.005 0.022 -10000 0 -0.099 22 22
GBP3 -0.021 0.21 0.32 21 -0.45 91 112
FOSL1 0.04 0.007 -10000 0 0 18 18
NFAT1-c-4/MAF/IRF4 0.09 0.15 -10000 0 -0.68 2 2
DGKA 0.025 0.12 0.29 7 -0.3 33 40
CREM 0.039 0.008 -10000 0 -0.002 20 20
NFAT1-c-4/PPARG 0.086 0.14 -10000 0 -0.69 2 2
CTLA4 0.023 0.1 -10000 0 -0.23 32 32
NFAT1-c-4 (dimer)/EGR1 0.062 0.15 -10000 0 -0.75 2 2
NFAT1-c-4 (dimer)/EGR4 0.094 0.15 -10000 0 -0.72 2 2
FOS 0.029 0.029 0.13 3 -0.042 7 10
IFNG 0.033 0.13 -10000 0 -0.49 7 7
T cell activation 0.054 0.12 0.6 1 -10000 0 1
MAF 0.036 0.015 -10000 0 0 80 80
T-helper 2 cell lineage commitment 0 0 -10000 0 -10000 0 0
activation-induced cell death of T cells -0.064 0.12 0.53 2 -0.5 22 24
TNF 0.048 0.13 0.46 2 -0.69 2 4
FASLG 0.055 0.16 0.7 1 -1 3 4
TBX21 0.046 0.013 0.093 1 -10000 0 1
BATF3 0 0 -10000 0 -10000 0 0
PRKCQ 0.037 0.018 -10000 0 -0.12 1 1
PTPN1 0.028 0.12 0.29 7 -0.27 29 36
NFAT1-c-4/ICER1 0.087 0.15 -10000 0 -0.72 2 2
GATA3 0.041 0.011 -10000 0 -10000 0 0
T-helper 1 cell differentiation 0.035 0.13 -10000 0 -0.49 7 7
IL2RA 0.05 0.15 -10000 0 -0.5 6 6
T-helper 1 cell lineage commitment 0 0 -10000 0 -10000 0 0
CASP3 0.023 0.12 0.27 2 -0.3 30 32
E2F1 0.031 0.05 -10000 0 -0.18 27 27
PPARG 0.039 0.01 -10000 0 -10000 0 0
SLC3A2 0.024 0.13 0.29 5 -0.3 36 41
IRF4 0.038 0.012 -10000 0 0 46 46
PTGS2 0.055 0.14 0.69 1 -0.72 2 3
CSF2 0.079 0.15 0.5 4 -0.69 2 6
JunB/Fra1/NFAT1-c-4 0.076 0.15 -10000 0 -0.69 2 2
IL4 0.033 0.14 -10000 0 -0.5 1 1
IL5 0.078 0.15 0.49 3 -0.69 2 5
IL2 0.054 0.12 0.6 1 -10000 0 1
IL3 0.036 0.078 -10000 0 -0.41 13 13
RNF128 0.022 0.042 0.2 4 -0.15 22 26
NFATC1 0.064 0.12 0.5 22 -0.53 2 24
CDK4 -0.077 0.29 0.47 3 -1.2 28 31
PTPRK 0.011 0.15 0.28 3 -0.39 45 48
IL8 0.048 0.14 0.58 3 -0.57 3 6
POU2F1 0.046 0.008 -10000 0 -10000 0 0
Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma 0.06 0.035 -9999 0 -0.096 15 15
MAPK9 0.009 0.002 -9999 0 0 39 39
adrenocorticotropin secretion -0.01 0.003 0 42 -10000 0 42
GNB1/GNG2 0.046 0.031 -9999 0 -0.11 16 16
GNB1 0.039 0.01 -9999 0 0 33 33
regulation of calcium ion transport via voltage-gated calcium channel activity 0 0 -9999 0 -10000 0 0
mol:GDP 0 0 -9999 0 -10000 0 0
MAPK14 0.009 0.002 -9999 0 0 20 20
Gs family/GTP 0.025 0.005 -9999 0 -10000 0 0
EntrezGene:2778 0 0 -9999 0 -10000 0 0
vasopressin secretion 0 0 -9999 0 -10000 0 0
G-protein coupled receptor activity 0 0 -9999 0 -10000 0 0
ChemicalAbstracts:86-01-1 0 0 -9999 0 -10000 0 0
glutamate secretion 0.002 0 -9999 0 -10000 0 0
GNAL 0.04 0.008 -9999 0 0 22 22
GNG2 0.039 0.009 -9999 0 0 29 29
CRH 0.038 0.011 -9999 0 0 42 42
mol:cortisol 0 0 -9999 0 -10000 0 0
MAPK8 0.009 0.002 -9999 0 0 29 29
MAPK11 0.007 0.004 -9999 0 0 157 157
S1P1 pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer 0.037 0.017 -10000 0 -0.13 3 3
PDGFRB 0.037 0.014 -10000 0 0 65 65
SPHK1 0.011 0.085 -10000 0 -0.63 9 9
mol:S1P 0.009 0.076 -10000 0 -0.53 9 9
S1P1/S1P/Gi 0.025 0.081 -10000 0 -0.31 18 18
GNAO1 0.035 0.017 -10000 0 -0.003 92 92
PDGFB-D/PDGFRB/PLCgamma1 0.013 0.1 0.25 7 -0.27 31 38
PLCG1 0.01 0.087 0.21 11 -0.3 19 30
mol:GTP 0 0 -10000 0 -10000 0 0
PDGFB-D/PDGFRB 0.037 0.014 -10000 0 0 65 65
GNAI2 0.04 0.012 -10000 0 -0.014 22 22
GNAI3 0.038 0.015 -10000 0 -0.006 54 54
GNAI1 0.034 0.018 -10000 0 -0.002 100 100
mol:GDP 0 0 -10000 0 -10000 0 0
EDG1 0.024 0.016 -10000 0 -0.12 3 3
S1P1/S1P 0.021 0.068 0.2 1 -0.33 11 12
negative regulation of cAMP metabolic process 0.025 0.08 -10000 0 -0.3 18 18
MAPK3 0.011 0.11 -10000 0 -0.47 14 14
calcium-dependent phospholipase C activity 0 0.002 -10000 0 -10000 0 0
Rac1/GDP 0.029 0.009 -10000 0 -0.12 1 1
RhoA/GDP 0.029 0.014 -10000 0 -0.12 4 4
KDR 0.043 0.01 -10000 0 -10000 0 0
PLCB2 0.016 0.064 -10000 0 -0.31 10 10
RAC1 0.039 0.009 -10000 0 0 28 28
RhoA/GTP 0.019 0.06 -10000 0 -0.28 12 12
receptor internalization 0.02 0.064 0.19 2 -0.31 11 13
PTGS2 0.003 0.15 0.34 1 -0.81 11 12
Rac1/GTP 0.019 0.06 -10000 0 -0.29 11 11
RHOA 0.04 0.006 -10000 0 0 13 13
VEGFA 0.004 0.002 -10000 0 -10000 0 0
negative regulation of T cell proliferation 0.025 0.08 -10000 0 -0.3 18 18
GO:0007205 0 0 -10000 0 -10000 0 0
GNAZ 0.038 0.015 -10000 0 -0.005 55 55
MAPK1 0.014 0.097 0.26 1 -0.44 12 13
S1P1/S1P/PDGFB-D/PDGFRB 0.032 0.076 0.23 2 -0.27 13 15
ABCC1 0.04 0.009 -10000 0 0 27 27
Arf6 trafficking events

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
SLC2A4 0.039 0.01 -10000 0 0 35 35
CLTC 0.011 0.086 -10000 0 -0.46 11 11
calcium ion-dependent exocytosis 0.016 0.046 0.18 2 -0.19 9 11
Dynamin 2/GTP 0.021 0.041 -10000 0 -0.11 44 44
EXOC4 0.038 0.011 -10000 0 0 41 41
CD59 0.009 0.057 -10000 0 -0.35 10 10
CPE 0.012 0.013 -10000 0 -0.11 4 4
CTNNB1 0.039 0.01 -10000 0 0 32 32
membrane fusion 0.004 0.033 0.11 2 -0.15 12 14
CTNND1 -0.009 0.066 0.17 50 -0.2 3 53
DNM2 0.036 0.014 -10000 0 0 72 72
mol:PI-4-5-P2 0.015 0.053 0.18 3 -0.22 12 15
TSHR 0.014 0.015 -10000 0 -0.11 7 7
INS 0.004 0.1 -10000 0 -0.45 26 26
BIN1 0.04 0.007 -10000 0 0 18 18
mol:Choline 0.004 0.033 0.11 2 -0.15 12 14
growth hormone secretagogue receptor activity 0 0 -10000 0 -10000 0 0
mol:GDP 0.014 0.013 -10000 0 -0.11 5 5
membrane depolarization 0 0 -10000 0 -10000 0 0
ARF6 0.04 0.007 -10000 0 0 16 16
mol:Ca2+ 0.021 0.041 -10000 0 -0.11 44 44
JUP 0.008 0.058 -10000 0 -0.35 9 9
ASAP2/amphiphysin II 0.047 0.023 -10000 0 -0.096 11 11
ARF6/GTP 0.028 0.019 -10000 0 -0.12 8 8
CDH1 0.006 0.063 -10000 0 -0.38 10 10
clathrin-independent pinocytosis 0.028 0.019 -10000 0 -0.12 8 8
MAPK8IP3 0.039 0.009 -10000 0 0 29 29
positive regulation of endocytosis 0.028 0.019 -10000 0 -0.12 8 8
EXOC2 0.038 0.011 -10000 0 0 41 41
substrate adhesion-dependent cell spreading 0.012 0.1 -10000 0 -0.27 46 46
insulin receptor binding 0 0 -10000 0 -10000 0 0
SPAG9 0.039 0.009 -10000 0 0 30 30
regulation of calcium-dependent cell-cell adhesion -0.031 0.081 0.33 12 -10000 0 12
positive regulation of phagocytosis 0.015 0.015 -10000 0 -0.11 7 7
ARF6/GTP/JIP3 0.05 0.024 -10000 0 -0.11 8 8
ACAP1 0.004 0.033 -10000 0 -0.17 8 8
mol:GTP 0 0 -10000 0 -10000 0 0
CHRM2 0.012 0.057 -10000 0 -0.33 10 10
clathrin heavy chain/ACAP1 0.012 0.074 0.25 1 -0.37 11 12
JIP4/KLC1 0.045 0.029 -10000 0 -0.097 19 19
EXOC1 0.038 0.011 -10000 0 0 46 46
exocyst 0.011 0.11 -10000 0 -0.28 46 46
RALA/GTP 0.027 0.02 -10000 0 -0.12 9 9
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex 0.047 0.032 -10000 0 -0.11 19 19
receptor recycling 0.028 0.019 -10000 0 -0.12 8 8
CTNNA1 -0.009 0.065 0.17 48 -0.2 3 51
NME1 0.014 0.013 -10000 0 -0.11 5 5
clathrin coat assembly 0.012 0.086 -10000 0 -0.46 11 11
IL2RA 0.012 0.055 -10000 0 -0.33 9 9
VAMP3 0.015 0.015 -10000 0 -0.11 7 7
GLUT4/clathrin heavy chain/ACAP1 0.035 0.079 -10000 0 -0.36 10 10
EXOC6 0.038 0.011 -10000 0 0 46 46
PLD1 0 0.048 -10000 0 -0.19 28 28
PLD2 0.014 0.025 -10000 0 -0.19 3 3
EXOC5 0.04 0.008 -10000 0 0 20 20
PIP5K1C 0.011 0.049 0.18 2 -0.22 11 13
SDC1 0.01 0.058 -10000 0 -0.35 10 10
ARF6/GDP 0.026 0.038 -10000 0 -0.11 35 35
EXOC7 0.04 0.007 -10000 0 0 18 18
E-cadherin/beta catenin 0.034 0.084 -10000 0 -0.34 12 12
mol:Phosphatidic acid 0.004 0.033 0.11 2 -0.15 12 14
endocytosis -0.046 0.023 0.096 11 -10000 0 11
SCAMP2 0.039 0.009 -10000 0 0 25 25
ADRB2 0.005 0.084 0.24 2 -0.43 11 13
EXOC3 0.037 0.012 -10000 0 0 55 55
ASAP2 0 0 -10000 0 -10000 0 0
Dynamin 2/GDP 0.025 0.045 0.19 4 -0.11 44 48
KLC1 0 0 -10000 0 -10000 0 0
AVPR2 0.006 0.083 0.25 1 -0.43 11 12
RALA 0.04 0.008 -10000 0 0 19 19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin 0.017 0.086 -10000 0 -0.37 12 12
Arf1 pathway

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
coatomer protein complex 0.018 0.042 0.15 49 -0.12 1 50
EntrezGene:79658 0 0 -10000 0 -10000 0 0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A 0.016 0.035 0.12 6 -0.16 3 9
AP2 0.039 0.043 -10000 0 -0.13 21 21
mol:DAG 0 0 -10000 0 -10000 0 0
Arfaptin 2/Rac/GTP 0.051 0.018 -10000 0 -0.11 1 1
CLTB 0.04 0.008 -10000 0 0 22 22
coatomer protein complex/ARF1/GTP/ER cargo protein 0.02 0.03 -10000 0 -0.15 13 13
CD4 0.032 0.017 -10000 0 0 121 121
CLTA 0.04 0.006 -10000 0 0 10 10
mol:GTP -0.003 0.003 0.013 5 -0.02 1 6
ARFGAP1 -0.009 0.003 0 56 -10000 0 56
mol:PI-4-5-P2 0.009 0.014 0.079 15 -10000 0 15
ARF1/GTP 0.021 0.012 0.078 1 -0.14 1 2
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein 0.022 0.05 0.17 45 -0.17 4 49
mol:Choline 0.008 0.014 0.079 15 -10000 0 15
mol:GDP 0 0 -10000 0 -10000 0 0
ARF1 0.039 0.012 -10000 0 0 45 45
DDEF1 0.004 0.009 0.079 6 -10000 0 6
ARF1/GDP 0.006 0.015 0.058 2 -0.087 8 10
AP2M1 0.032 0.017 -10000 0 0 125 125
EntrezGene:1313 0 0 -10000 0 -10000 0 0
actin filament polymerization -0.009 0.017 0.049 11 -0.1 2 13
Rac/GTP 0.029 0.01 -10000 0 -0.13 1 1
ARF1/GTP/GGA3/ARF-GAP1 0.046 0.024 -10000 0 -0.1 1 1
ARFIP2 0.033 0.021 -10000 0 -0.039 36 36
COPA 0.039 0.009 -10000 0 0 26 26
RAC1 0.039 0.009 -10000 0 0 28 28
ARF1/GTP/coatomer protein complex 0.015 0.038 0.14 2 -0.2 10 12
ARF1/GTP/ARHGAP10 0.025 0.01 -10000 0 -0.11 1 1
GGA3 0.04 0.008 -10000 0 0 21 21
ARF1/GTP/Membrin 0.023 0.044 -10000 0 -0.22 14 14
AP2A1 0.039 0.01 -10000 0 0 32 32
coatomer protein complex/ARF1/GTP/ARF-GAP1 0.012 0.032 -10000 0 -0.17 11 11
ARF1/GDP/Membrin 0.029 0.051 -10000 0 -0.25 15 15
Arfaptin 2/Rac/GDP 0.05 0.018 -10000 0 -0.11 1 1
CYTH2 -0.003 0.003 0.013 5 -0.02 1 6
ARF1/GTP/GGA3 0.048 0.02 -10000 0 -0.12 2 2
mol:ATP 0 0 -10000 0 -10000 0 0
Rac/GDP 0.029 0.009 -10000 0 -0.12 1 1
mol:Brefeldin A 0 0 -10000 0 -10000 0 0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP 0.005 0.055 -10000 0 -0.3 7 7
PLD2 0.008 0.014 0.079 15 -10000 0 15
ARF-GAP1/v-SNARE -0.009 0.003 0 56 -10000 0 56
PIP5K1A 0.009 0.014 0.079 15 -10000 0 15
ARF1/GTP/Membrin/GBF1/p115 0.017 0.026 -10000 0 -0.074 22 22
mol:Phosphatic acid 0 0 -10000 0 -10000 0 0
mol:Phosphatidic acid 0.008 0.014 0.079 15 -10000 0 15
KDEL Receptor/Ligand/ARF-GAP1 -0.009 0.003 0 56 -10000 0 56
GOSR2 0.013 0.036 -10000 0 -0.31 6 6
USO1 0.003 0.007 0.04 17 -0.029 1 18
GBF1 0.005 0.066 -10000 0 -0.35 18 18
ARF1/GTP/Arfaptin 2 0.05 0.019 -10000 0 -0.12 1 1
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex 0.038 0.063 -10000 0 -0.12 45 45
Signaling events mediated by Stem cell factor receptor (c-Kit)

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
MAP4K1 0.027 0.078 0.3 10 -0.29 1 11
CRKL 0.018 0.064 0.25 2 -0.34 2 4
HRAS 0.028 0.076 0.24 2 -0.29 5 7
mol:PIP3 0.015 0.11 0.31 4 -0.38 15 19
SPRED1 0.035 0.014 -10000 0 0 78 78
SPRED2 0.04 0.008 -10000 0 0 22 22
GAB1 0.018 0.054 -10000 0 -0.31 1 1
FOXO3 0.02 0.093 -10000 0 -0.42 11 11
AKT1 0.021 0.098 -10000 0 -0.45 11 11
BAD 0.016 0.094 -10000 0 -0.42 11 11
megakaryocyte differentiation 0.021 0.057 0.24 1 -0.3 1 2
GSK3B 0.02 0.097 0.28 5 -0.41 11 16
RAF1 0.023 0.073 0.25 7 -0.27 3 10
SHC1 0.039 0.008 -10000 0 0 23 23
STAT3 0.017 0.06 -10000 0 -0.44 2 2
STAT1 0.027 0.11 -10000 0 -0.92 3 3
HRAS/SPRED1 0.034 0.082 0.26 3 -0.31 3 6
cell proliferation 0.017 0.062 0.25 2 -0.43 2 4
PIK3CA 0.029 0.019 -10000 0 0 166 166
TEC 0.033 0.017 -10000 0 0 114 114
RPS6KB1 0.022 0.094 -10000 0 -0.38 7 7
HRAS/SPRED2 0.039 0.082 0.25 3 -0.27 4 7
LYN/TEC/p62DOK 0.038 0.095 -10000 0 -0.36 4 4
MAPK3 0.016 0.063 0.23 6 -0.26 3 9
STAP1 0.02 0.059 -10000 0 -0.43 2 2
GRAP2 0.037 0.013 -10000 0 0 56 56
JAK2 0.026 0.11 -10000 0 -0.76 3 3
STAT1 (dimer) 0.029 0.11 -10000 0 -0.9 3 3
mol:Gleevec -0.002 0.003 -10000 0 -10000 0 0
GRB2/SOCS1/VAV1 0.058 0.089 -10000 0 -0.38 3 3
actin filament polymerization 0.02 0.06 -10000 0 -0.42 2 2
LYN 0.035 0.015 -10000 0 0 83 83
STAP1/STAT5A (dimer) 0.017 0.094 -10000 0 -0.55 4 4
PIK3R1 0.034 0.016 -10000 0 0 99 99
CBL/CRKL/GRB2 0.05 0.084 0.29 1 -0.36 2 3
PI3K 0.023 0.099 -10000 0 -0.33 10 10
PTEN 0.038 0.01 -10000 0 0 36 36
SCF/KIT/EPO/EPOR 0.056 0.13 -10000 0 -1.3 2 2
MAPK8 0.016 0.063 0.25 2 -0.44 2 4
STAT3 (dimer) 0.017 0.059 -10000 0 -0.43 2 2
positive regulation of transcription 0.015 0.057 0.21 6 -0.24 2 8
mol:GDP 0.037 0.082 -10000 0 -0.34 3 3
PIK3C2B 0.016 0.062 -10000 0 -0.44 2 2
CBL/CRKL 0.036 0.077 0.28 1 -0.36 2 3
FER 0.018 0.06 -10000 0 -0.44 2 2
SH2B3 0.02 0.059 -10000 0 -0.43 2 2
PDPK1 0.014 0.1 0.3 5 -0.33 15 20
SNAI2 0.021 0.067 0.24 2 -0.5 2 4
positive regulation of cell proliferation 0.019 0.11 -10000 0 -0.74 3 3
KITLG 0.043 0.014 -10000 0 -0.042 3 3
cell motility 0.019 0.11 -10000 0 -0.74 3 3
PTPN6 0.034 0.015 -10000 0 -0.005 67 67
EPOR 0.006 0.17 -10000 0 -0.99 2 2
STAT5A (dimer) 0.021 0.1 -10000 0 -0.56 4 4
SOCS1 0.037 0.012 -10000 0 0 51 51
cell migration -0.017 0.058 0.43 2 -10000 0 2
SOS1 0.037 0.012 -10000 0 0 51 51
EPO 0.043 0.01 -10000 0 -0.036 3 3
VAV1 0.036 0.014 -10000 0 0 69 69
GRB10 0.017 0.061 -10000 0 -0.44 2 2
PTPN11 0.037 0.011 -10000 0 -0.004 33 33
SCF/KIT 0.024 0.064 -10000 0 -0.45 2 2
GO:0007205 -0.002 0.004 -10000 0 -10000 0 0
MAP2K1 0.014 0.064 0.24 6 -0.24 2 8
CBL 0.04 0.008 -10000 0 0 20 20
KIT 0.015 0.16 -10000 0 -0.73 5 5
MAP2K2 0.014 0.061 0.24 6 -0.24 2 8
SHC/Grb2/SOS1 0.063 0.09 -10000 0 -0.4 2 2
STAT5A 0.024 0.097 -10000 0 -0.58 4 4
GRB2 0.04 0.008 -10000 0 0 21 21
response to radiation 0.025 0.07 0.24 3 -0.49 2 5
SHC/GRAP2 0.052 0.023 -10000 0 -0.13 1 1
PTPRO 0.019 0.055 0.24 1 -0.3 1 2
SH2B2 0.02 0.059 -10000 0 -0.43 2 2
DOK1 0.04 0.008 -10000 0 0 22 22
MATK 0.016 0.059 -10000 0 -0.44 2 2
CREBBP 0.058 0.029 -10000 0 -0.14 3 3
BCL2 -0.013 0.21 -10000 0 -0.67 22 22
Glypican 2 network

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
MDK 0.039 0.008 -9999 0 0 23 23
GPC2 0.04 0.006 -9999 0 0 13 13
GPC2/Midkine 0.054 0.032 -9999 0 -0.13 14 14
neuron projection morphogenesis 0.054 0.032 -9999 0 -0.13 14 14
Visual signal transduction: Rods

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

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

Entity Mean Std.Dev Mean.of.Up.Perturbations Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
mol:K + 0.04 0.007 -10000 0 0 15 15
GNAT1/GTP 0.03 0.005 -10000 0 -10000 0 0
Metarhodopsin II/Arrestin 0.052 0.013 -10000 0 -10000 0 0
PDE6G/GNAT1/GTP 0.049 0.02 -10000 0 -0.11 2 2
mol:GTP 0 0 -10000 0 -10000 0 0
absorption of light 0 0 -10000 0 -10000 0 0
GNAT1 0.04 0.006 -10000 0 0 13 13
GRK1 0 0 -10000 0 -10000 0 0
CNG Channel 0.066 0.037 -10000 0 -0.11 2 2
mol:Na + 0.068 0.041 -10000 0 -0.11 1 1
mol:ADP 0 0 -10000 0 -10000 0 0
RGS9-1/Gbeta5/R9AP 0.067 0.034 -10000 0 -0.12 1 1
mol:GDP 0 0 -10000 0 -10000 0 0
cGMP/CNG Channel 0.084 0.049 -10000 0 -0.11 1 1
CNGB1 0.038 0.01 -10000 0 0 38 38
RDH5 0.036 0.013 -10000 0 0 65 65
SAG 0.04 0.006 -10000 0 0 12 12
mol:Ca2+ -0.017 0.081 0.32 19 -10000 0 19
Na + (4 Units) 0.056 0.037 -10000 0 -0.11 1 1
RGS9 0.038 0.01 -10000 0 0 37 37
GNB1/GNGT1 0.054 0.024 -10000 0 -0.13 4 4
GNAT1/GDP 0.079 0.038 -10000 0 -0.1 1 1
GUCY2D 0.038 0.011 -10000 0 0 42 42
GNGT1 0.039 0.009 -10000 0 0 26 26
GUCY2F 0.041 0.002 -10000 0 0 1 1
GNB5 0.039 0.008 -10000 0 0 23 23
mol:GMP (4 units) 0.035 0.023 0.16 7 -0.1 2 9
mol:11-cis-retinal 0.036 0.013 -10000 0 0 65 65
mol:cGMP 0.075 0.034 0.2 3 -0.11 1 4
GNB1 0.039 0.01 -10000 0 0 33 33
Rhodopsin 0.05 0.03 -10000 0 -0.13 7 7
SLC24A1 0.04 0.007 -10000 0 0 15 15
CNGA1 0.04 0.008 -10000 0 0 20 20
Metarhodopsin II 0.025 0.005 -10000 0 -10000 0 0
mol:Ca ++ 0 0 -10000 0 -10000 0 0
GC1/GCAP Family 0.09 0.038 -10000 0 -0.11 1 1
RGS9BP 0.037 0.013 -10000 0 0 56 56
Metarhodopsin II/Transducin 0.023 0.02 -10000 0 -0.14 6 6
GCAP Family/Ca ++ 0.072 0.024 -10000 0 -0.1 1 1
PDE6A/B 0.055 0.019 -10000 0 -10000 0 0
mol:Pi 0.066 0.033 -10000 0 -0.12 1 1
mol:all-trans-retinal 0 0 -10000 0 -10000 0 0
Transducin 0.07 0.029 -10000 0 -0.1 4 4
PDE6B 0.038 0.011 -10000 0 0 45 45
PDE6A 0.04 0.007 -10000 0 0 15 15
PDE6G 0.037 0.012 -10000 0 0 55 55
RHO 0.04 0.008 -10000 0 0 20 20
PDE6 0.09 0.056 -10000 0 -0.15 2 2
GUCA1A 0.039 0.008 -10000 0 0 24 24
GC2/GCAP Family 0.097 0.031 -10000 0 -0.11 1 1
GUCA1C 0.039 0.009 -10000 0 0 27 27
GUCA1B 0.04 0.008 -10000 0 0 21 21
Visual signal transduction: Cones

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 Number.of.Up.Perturbations Mean.of.Down.Perturbations Number.of.Down.Perturbations Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin 0.062 0.027 -10000 0 -0.096 1 1
RGS9BP 0.037 0.013 -10000 0 0 56 56
mol:GTP 0 0 -10000 0 -10000 0 0
GRK1 0 0 -10000 0 -10000 0 0
mol:Na + 0.05 0.016 -10000 0 -10000 0 0
mol:ADP -0.01 0.003 -10000 0 -10000 0 0
GNAT2 0.041 0.004 -10000 0 0 6 6
RGS9-1/Gbeta5/R9AP 0.067 0.034 -10000 0 -0.12 1 1
mol:GDP 0 0 -10000 0 -10000 0 0
PDE6H/GNAT2/GTP 0.05 0.017 -10000 0 -10000 0 0
GRK7 0.038 0.011 -10000 0 0 40 40
CNGB3 0.038 0.012 -10000 0 0 49 49
Cone Metarhodopsin II/X-Arrestin 0.03 0.001 -10000 0 -10000 0 0
mol:Ca2+ -0.004 0.055 0.19 40 -10000 0 40
Cone PDE6 0.089 0.055 -10000 0 -0.11 1 1
Cone Metarhodopsin II 0.024 0.007 -10000 0 -10000 0 0
Na + (4 Units) 0.067 0.028 -10000 0 -10000 0 0
GNAT2/GDP 0.08 0.037 -10000 0 -0.1 1 1
GNB5 0.039 0.008 -10000 0 0 23 23
mol:GMP (4 units) -0.003 0.058 0.19 45 -10000 0 45
Cone Transducin 0.067 0.029 -10000 0 -0.1 1 1
SLC24A2 0.039 0.01 -10000 0 0 33 33
GNB3/GNGT2 0.052 0.022 -10000 0 -0.13 1 1
GNB3 0.037 0.012 -10000 0 0 55 55
GNAT2/GTP 0.03 0.003 -10000 0 -10000 0 0
CNGA3 0.041 0.004 -10000 0 0 4 4
ARR3 0.041 0.002 -10000 0 0 1 1
absorption of light 0 0 -10000 0 -10000 0 0
cGMP/Cone CNG Channel 0.05 0.016 -10000 0 -10000 0 0
mol:Pi 0.066 0.033 -10000 0 -0.12 1 1
Cone CNG Channel 0.081 0.043 -10000 0 -10000 0 0
mol:all-trans-retinal 0 0 -10000 0 -10000 0 0
mol:K + 0.039 0.01 -10000 0 0 33 33
RGS9 0.038 0.01 -10000 0 0 37 37
PDE6C 0.04 0.007 -10000 0 0 18 18
GNGT2 0.039 0.008 -10000 0 0 23 23
mol:cGMP (4 units) 0 0 -10000 0 -10000 0 0
PDE6H 0.037 0.012 -10000 0 0 50 50
Methods & Data
Input

  • Expression Data Normalization = Tumor samples were used to median center the expression data used in this analysis.

  • Expression File Used = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MergeDataFilesPipeline/OV/856530/1.GDAC_MergeDataFiles.Finished/OV.exon__huex_1_0_st_v2__lbl_gov__Level_3__quantile_normalization_gene__data.data.txt

  • Copy Number File Used = /xchip/cga/gdac-prod/tcga-gdac/jobResults/writeReducedSegments/OV/868533/1.GetReducedSegments.Finished/OV.RS.tsv

Data Sets and Pathway Interactions

Both copy number and expression data are incorporated into PARADIGM's inference. Whenever normal tissue controls are available for analysis in the expression data, each patient's gene-value is normalized by subtracting the gene's median level observed in the normal control. Copy number data is also normalized to reflect the difference in copy number between a gene's levels detected in tumor versus control (e.g. blood normal). The collection of pathways used by PARADIGM includes those from NCI-PID on September 15, 2009 containing 131 pathways, 11,563 interactions, and 7,204 entities. All gene identifiers were translated into HUGO standard identifiers wherever possible. We refer to molecular entities as "concepts," which include gene products such as proteins and miRNAs, small molecules, protein complexes, and abstract concepts. Each concept is represented as "node" in PARADIGM's graphical model. The abstract concepts correspond to general cellular processes (such as "apoptosis" or "DNA damage response") and families of genes that share functional activity such as the RAS family of signal transducers. Various types of concept-concept interactions are included in the pathways including protein-protein interactions, transcriptional regulatory interactions, and protein modifications such as phosphorylation and ubiquitinylation interactions.

Pathway Inference Method

The PARADIGM algorithm (described in PMID: 20529912) assigns an integrated pathway level (IPL) reflecting the activity of a concept determined through a belief propagation strategy. The belief propagation is given the copy number and gene expression measurements of all of the genes and iteratively updates hidden states reflecting the activities of all of the genes in a pathway so as to maximize the likelihood of the observed data given the interactions in the pathway. In the end, the inferred level of a concept reflects both the data observed for the concept and the neighborhood of activity surrounding the concept.

Determining significantly altered levels

The significance of the IPL obtained for each concept in each patient sample is assessed using a permutation analysis. Importantly, the permutation analysis preserves data tuples so as to preserve any implicit correlations between the different data modalities. For example, genes that are deleted have concomitantly lower expression levels. Preserving the copy number and expression pairs therefore retains this data property. The simulation therefore makes "null samples" by permuting data tuples across all of the genes in the genome so that each gene in a null sample is associated with a random tuple of another gene with equal probability. This approach has the added benefit of preserving the pathway structure so that every observed IPL can be compared to a distribution of random IPLs derived from exactly the same interaction context. PARADIGM inferences are then obtained for 1000 "null" patients and serve as a background distribution to contrast the observed IPLs against. Pathway concepts are excluded from further analysis if they did not obtain a minimum IPL of 0.5 in any patient sample both observed or simulated.

An IPL I(i,j) for concept i in sample j, is considered to be deviated if its absolute level is two standard deviations from the average level observed for concept i in the 1000 null samples. The degree to which a concept has significantly altered levels across a patient cohort is summarized in the proportion of deviated samples (PDS) score. For example, a protein with a PDS of 0.10 reflects that the protein's level of activity was inferred to be significantly higher or lower in tumors compared to normal in 10% of the patient samples. An average PDS for a pathway is also reported by computing the mean PDS over all concepts in the pathway.

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References
[2] Charles J. Vaske, Stephen C. Benz, J. Zachary Sanborn, Dent Earl, Christopher Szeto, Jingchun Zhu, David Haussler, and Joshua M. Stuart, Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM, Bioinformatics 12(26):237-245 (2010)
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