Signaling Pathway Impact Analysis (SPIA) based on over-representation and signaling perturbations accumulation

Description

This function implements the SPIA algorithm to analyze KEGG signaling pathways.

Usage

spia(de=NULL,all=NULL,organism="hsa",data.dir=NULL,pathids=NULL,nB=2000,plots=FALSE,verbose=TRUE,beta=NULL,combine="fisher")

Arguments

Details

See cited documents for more details.

Value

A data frame containing the ranked pathways and various statistics: pSize is the number of genes on the pathway; NDE is the number of DE genes per pathway; tA is the observed total preturbation accumulation in the pathway; pNDE is the probability to observe at least NDE genes on the pathway using a hypergeometric model; pPERT is the probability to observe a total accumulation more extreme than tA only by chance; pG is the p-value obtained by combining pNDE and pPERT; pGFdr and pGFWER are the False Discovery Rate and respectively Bonferroni adjusted global p-values; and the Status gives the direction in which the pathway is perturbed (activated or inhibited). KEGGLINK gives a web link to the KEGG website that displays the pathway image with the differentially expressed genes highlighted in red.

Author(s)

Adi Laurentiu Tarca <atarca@med.wayne.edu>, Purvesh Khatri, Sorin Draghici

References

Adi L. Tarca, Sorin Draghici, Purvesh Khatri, et. al, A Signaling Pathway Impact Analysis for Microarray Experiments, 2008, Bioinformatics, 2009, 25(1):75-82.

Purvesh Khatri, Sorin Draghici, Adi L. Tarca, Sonia S. Hassan, Roberto Romero. A system biology approach for the steady-state analysis of gene signaling networks. Progress in Pattern Recognition, Image Analysis and Applications, Lecture Notes in Computer Science. 4756:32-41, November 2007.

Draghici, S., Khatri, P., Tarca, A.L., Amin, K., Done, A., Voichita, C., Georgescu, C., Romero, R.: A systems biology approach for pathway level analysis. Genome Research, 17, 2007.

See Also

plotP

Examples

# Example using a colorectal cancer dataset obtained using Affymetrix geneChip technology (GEE GSE4107).
# Suppose that proper preprocessing was performed and a two group moderated t-test was applied. The topTable 
# result from limma package for this data set is called "top".
#The following lines will annotate each probeset to an entrez ID identifier, will keep the most significant probeset for each 
#gene ID and retain those with FDR<0.05 as differentially expressed.
#You can run these lines if hgu133plus2.db package is available

#data(colorectalcancer)
#x <- hgu133plus2ENTREZID 
#top$ENTREZ<-unlist(as.list(x[top$ID]))
#top<-top[!is.na(top$ENTREZ),]
#top<-top[!duplicated(top$ENTREZ),]
#tg1<-top[top$adj.P.Val<0.1,]
#DE_Colorectal=tg1$logFC
#names(DE_Colorectal)<-as.vector(tg1$ENTREZ)
#ALL_Colorectal=top$ENTREZ

data(colorectalcancer)

# pathway analysis using SPIA; # use nB=2000 or higher for more accurate results
#uses older version of KEGG signalimng pathways graphs
res<-spia(de=DE_Colorectal, all=ALL_Colorectal, organism="hsa",beta=NULL,nB=2000,plots=FALSE, verbose=TRUE,combine="fisher")
res
# Create the evidence plot
plotP(res)

#now combine pNDE and pPERT using the normal inversion method without running spia function again
res$pG=combfunc(res$pNDE,res$pPERT,combine="norminv")
res$pGFdr=p.adjust(res$pG,"fdr")
res$pGFWER=p.adjust(res$pG,"bonferroni")
plotP(res,threshold=0.05)
#highlight the colorectal cancer pathway in green
points(I(-log(pPERT))~I(-log(pNDE)),data=res[res$ID=="05210",],col="green",pch=19,cex=1.5)

#run SPIA using pathways data generated from (up-to-date) xml files that you can obtain from 
#KEGG ftp or by downloading  them from each pathway's web page:
# e.g. go to http://www.genome.jp/kegg/pathway/hsa/hsa04010.html  and click on DOwnload KGML
#to get the xml file for pathway 4010

makeSPIAdata(kgml.path=system.file("extdata/keggxml/hsa",package="SPIA"),organism="hsa",out.path="./")

res<-spia(de=DE_Colorectal, all=ALL_Colorectal, organism="hsa",data.dir="./")
res

Results

R version 3.3.1 (2016-06-21) -- "Bug in Your Hair"
Copyright (C) 2016 The R Foundation for Statistical Computing
Platform: x86_64-pc-linux-gnu (64-bit)

R is free software and comes with ABSOLUTELY NO WARRANTY.
You are welcome to redistribute it under certain conditions.
Type 'license()' or 'licence()' for distribution details.

R is a collaborative project with many contributors.
Type 'contributors()' for more information and
'citation()' on how to cite R or R packages in publications.

Type 'demo()' for some demos, 'help()' for on-line help, or
'help.start()' for an HTML browser interface to help.
Type 'q()' to quit R.

> library(SPIA)
Loading required package: KEGGgraph

Attaching package: 'KEGGgraph'

The following object is masked from 'package:graphics':

    plot

> png(filename="/home/ddbj/snapshot/RGM3/R_BC/result/SPIA/spia.Rd_%03d_medium.png", width=480, height=480)
> ### Name: spia
> ### Title: Signaling Pathway Impact Analysis (SPIA) based on
> ###   over-representation and signaling perturbations accumulation
> ### Aliases: spia
> ### Keywords: nonparametric methods
> 
> ### ** Examples
> 
> # Example using a colorectal cancer dataset obtained using Affymetrix geneChip technology (GEE GSE4107).
> # Suppose that proper preprocessing was performed and a two group moderated t-test was applied. The topTable 
> # result from limma package for this data set is called "top".
> #The following lines will annotate each probeset to an entrez ID identifier, will keep the most significant probeset for each 
> #gene ID and retain those with FDR<0.05 as differentially expressed.
> #You can run these lines if hgu133plus2.db package is available
> 
> #data(colorectalcancer)
> #x <- hgu133plus2ENTREZID 
> #top$ENTREZ<-unlist(as.list(x[top$ID]))
> #top<-top[!is.na(top$ENTREZ),]
> #top<-top[!duplicated(top$ENTREZ),]
> #tg1<-top[top$adj.P.Val<0.1,]
> #DE_Colorectal=tg1$logFC
> #names(DE_Colorectal)<-as.vector(tg1$ENTREZ)
> #ALL_Colorectal=top$ENTREZ
> 
> data(colorectalcancer)
> 
> # pathway analysis using SPIA; # use nB=2000 or higher for more accurate results
> #uses older version of KEGG signalimng pathways graphs
> res<-spia(de=DE_Colorectal, all=ALL_Colorectal, organism="hsa",beta=NULL,nB=2000,plots=FALSE, verbose=TRUE,combine="fisher")

Done pathway 1 : RNA transport..
Done pathway 2 : RNA degradation..
Done pathway 3 : PPAR signaling pathway..
Done pathway 4 : Fanconi anemia pathway..
Done pathway 5 : MAPK signaling pathway..
Done pathway 6 : ErbB signaling pathway..
Done pathway 7 : Calcium signaling pathway..
Done pathway 8 : Cytokine-cytokine receptor int..
Done pathway 9 : Chemokine signaling pathway..
Done pathway 10 : NF-kappa B signaling pathway..
Done pathway 11 : Phosphatidylinositol signaling..
Done pathway 12 : Neuroactive ligand-receptor in..
Done pathway 13 : Cell cycle..
Done pathway 14 : Oocyte meiosis..
Done pathway 15 : p53 signaling pathway..
Done pathway 16 : Sulfur relay system..
Done pathway 17 : SNARE interactions in vesicula..
Done pathway 18 : Regulation of autophagy..
Done pathway 19 : Protein processing in endoplas..
Done pathway 20 : Lysosome..
Done pathway 21 : mTOR signaling pathway..
Done pathway 22 : Apoptosis..
Done pathway 23 : Vascular smooth muscle contrac..
Done pathway 24 : Wnt signaling pathway..
Done pathway 25 : Dorso-ventral axis formation..
Done pathway 26 : Notch signaling pathway..
Done pathway 27 : Hedgehog signaling pathway..
Done pathway 28 : TGF-beta signaling pathway..
Done pathway 29 : Axon guidance..
Done pathway 30 : VEGF signaling pathway..
Done pathway 31 : Osteoclast differentiation..
Done pathway 32 : Focal adhesion..
Done pathway 33 : ECM-receptor interaction..
Done pathway 34 : Cell adhesion molecules (CAMs)..
Done pathway 35 : Adherens junction..
Done pathway 36 : Tight junction..
Done pathway 37 : Gap junction..
Done pathway 38 : Complement and coagulation cas..
Done pathway 39 : Antigen processing and present..
Done pathway 40 : Toll-like receptor signaling p..
Done pathway 41 : NOD-like receptor signaling pa..
Done pathway 42 : RIG-I-like receptor signaling ..
Done pathway 43 : Cytosolic DNA-sensing pathway..
Done pathway 44 : Jak-STAT signaling pathway..
Done pathway 45 : Natural killer cell mediated c..
Done pathway 46 : T cell receptor signaling path..
Done pathway 47 : B cell receptor signaling path..
Done pathway 48 : Fc epsilon RI signaling pathwa..
Done pathway 49 : Fc gamma R-mediated phagocytos..
Done pathway 50 : Leukocyte transendothelial mig..
Done pathway 51 : Intestinal immune network for ..
Done pathway 52 : Circadian rhythm - mammal..
Done pathway 53 : Long-term potentiation..
Done pathway 54 : Neurotrophin signaling pathway..
Done pathway 55 : Retrograde endocannabinoid sig..
Done pathway 56 : Glutamatergic synapse..
Done pathway 57 : Cholinergic synapse..
Done pathway 58 : Serotonergic synapse..
Done pathway 59 : GABAergic synapse..
Done pathway 60 : Dopaminergic synapse..
Done pathway 61 : Long-term depression..
Done pathway 62 : Olfactory transduction..
Done pathway 63 : Taste transduction..
Done pathway 64 : Phototransduction..
Done pathway 65 : Regulation of actin cytoskelet..
Done pathway 66 : Insulin signaling pathway..
Done pathway 67 : GnRH signaling pathway..
Done pathway 68 : Progesterone-mediated oocyte m..
Done pathway 69 : Melanogenesis..
Done pathway 70 : Adipocytokine signaling pathwa..
Done pathway 71 : Type II diabetes mellitus..
Done pathway 72 : Type I diabetes mellitus..
Done pathway 73 : Maturity onset diabetes of the..
Done pathway 74 : Aldosterone-regulated sodium r..
Done pathway 75 : Endocrine and other factor-reg..
Done pathway 76 : Vasopressin-regulated water re..
Done pathway 77 : Salivary secretion..
Done pathway 78 : Gastric acid secretion..
Done pathway 79 : Pancreatic secretion..
Done pathway 80 : Carbohydrate digestion and abs..
Done pathway 81 : Bile secretion..
Done pathway 82 : Mineral absorption..
Done pathway 83 : Alzheimer's disease..
Done pathway 84 : Parkinson's disease..
Done pathway 85 : Amyotrophic lateral sclerosis ..
Done pathway 86 : Huntington's disease..
Done pathway 87 : Prion diseases..
Done pathway 88 : Cocaine addiction..
Done pathway 89 : Amphetamine addiction..
Done pathway 90 : Morphine addiction..
Done pathway 91 : Alcoholism..
Done pathway 92 : Bacterial invasion of epitheli..
Done pathway 93 : Vibrio cholerae infection..
Done pathway 94 : Epithelial cell signaling in H..
Done pathway 95 : Pathogenic Escherichia coli in..
Done pathway 96 : Shigellosis..
Done pathway 97 : Salmonella infection..
Done pathway 98 : Pertussis..
Done pathway 99 : Legionellosis..
Done pathway 100 : Leishmaniasis..
Done pathway 101 : Chagas disease (American trypa..
Done pathway 102 : African trypanosomiasis..
Done pathway 103 : Malaria..
Done pathway 104 : Toxoplasmosis..
Done pathway 105 : Amoebiasis..
Done pathway 106 : Staphylococcus aureus infectio..
Done pathway 107 : Tuberculosis..
Done pathway 108 : Hepatitis C..
Done pathway 109 : Measles..
Done pathway 110 : Influenza A..
Done pathway 111 : HTLV-I infection..
Done pathway 112 : Herpes simplex infection..
Done pathway 113 : Epstein-Barr virus infection..
Done pathway 114 : Pathways in cancer..
Done pathway 115 : Transcriptional misregulation ..
Done pathway 116 : Viral carcinogenesis..
Done pathway 117 : Colorectal cancer..
Done pathway 118 : Renal cell carcinoma..
Done pathway 119 : Pancreatic cancer..
Done pathway 120 : Endometrial cancer..
Done pathway 121 : Glioma..
Done pathway 122 : Prostate cancer..
Done pathway 123 : Thyroid cancer..
Done pathway 124 : Basal cell carcinoma..
Done pathway 125 : Melanoma..
Done pathway 126 : Bladder cancer..
Done pathway 127 : Chronic myeloid leukemia..
Done pathway 128 : Acute myeloid leukemia..
Done pathway 129 : Small cell lung cancer..
Done pathway 130 : Non-small cell lung cancer..
Done pathway 131 : Asthma..
Done pathway 132 : Autoimmune thyroid disease..
Done pathway 133 : Systemic lupus erythematosus..
Done pathway 134 : Rheumatoid arthritis..
Done pathway 135 : Allograft rejection..
Done pathway 136 : Graft-versus-host disease..
Done pathway 137 : Arrhythmogenic right ventricul..
Done pathway 138 : Dilated cardiomyopathy..
Done pathway 139 : Viral myocarditis..> res
                                                          Name    ID pSize NDE
1                                               Focal adhesion 04510   178  89
2                                          Alzheimer's disease 05010   150  85
3                                     ECM-receptor interaction 04512    74  42
4                                          Parkinson's disease 05012   110  65
5                                           Pathways in cancer 05200   302 126
6                                         Huntington's disease 05016   169  80
7                                       PPAR signaling pathway 03320    66  37
8                                                Axon guidance 04360   119  59
9                             Fc gamma R-mediated phagocytosis 04666    80  42
10                                      MAPK signaling pathway 04010   246 104
11                            Regulation of actin cytoskeleton 04810   192  85
12                                      Small cell lung cancer 05222    73  33
13                                       Glutamatergic synapse 04724   114  45
14                      Bacterial invasion of epithelial cells 05100    62  32
15                                       Wnt signaling pathway 04310   139  60
16                     Transcriptional misregulation in cancer 05202   153  63
17                                        Renal cell carcinoma 05211    64  29
18                             Staphylococcus aureus infection 05150    43  20
19                                           Colorectal cancer 05210    57  24
20                           B cell receptor signaling pathway 04662    71  32
21                                      ErbB signaling pathway 04012    77  34
22                       Pathogenic Escherichia coli infection 05130    46  20
23                                                    Lysosome 04142   116  48
24                                        Salmonella infection 05132    76  35
25                                   Circadian rhythm - mammal 04710    16  10
26                        Leukocyte transendothelial migration 04670   101  42
27                                                     Malaria 05144    45  23
28                       Phosphatidylinositol signaling system 04070    73  31
29                                Systemic lupus erythematosus 05322    98  34
30                      Cytokine-cytokine receptor interaction 04060   240  73
31                                     Notch signaling pathway 04330    46  23
32                                              Tight junction 04530   117  49
33                                               Legionellosis 05134    47  22
34                                         Cholinergic synapse 04725   103  42
35                                               Toxoplasmosis 05145   112  47
36      Arrhythmogenic right ventricular cardiomyopathy (ARVC) 05412    69  31
37                                                Gap junction 04540    80  35
38                                         Sulfur relay system 04122     8   4
39                                      Dilated cardiomyopathy 05414    83  32
40                                 Chemokine signaling pathway 04062   162  53
41                                                 Hepatitis C 05160   121  39
42                                          Endometrial cancer 05213    47  21
43                                                 Influenza A 05164   158  61
44                                          Morphine addiction 05032    84  30
45                                     African trypanosomiasis 05143    30   9
46                             Fc epsilon RI signaling pathway 04664    70  25
47                          Vascular smooth muscle contraction 04270   100  41
48                                      VEGF signaling pathway 04370    65  24
49                                           GABAergic synapse 04727    84  30
50                                                   Apoptosis 04210    82  30
51                                   Insulin signaling pathway 04910   123  46
52                                Dorso-ventral axis formation 04320    21  11
53                              Neurotrophin signaling pathway 04722   112  45
54                                        Basal cell carcinoma 05217    51  18
55                           T cell receptor signaling pathway 04660   102  37
56                                                 Shigellosis 05131    56  24
57                                            HTLV-I infection 05166   241  85
58                                                  Amoebiasis 05146    93  38
59                 Protein processing in endoplasmic reticulum 04141   151  55
60                                                   Pertussis 05133    64  27
61                                              Prion diseases 05020    33  13
62                                                    Melanoma 05218    68  23
63                                           Viral myocarditis 05416    60  25
64                                  Non-small cell lung cancer 05223    51  18
65                   SNARE interactions in vesicular transport 04130    34  16
66                                              Bladder cancer 05219    39  15
67                                        Serotonergic synapse 04726   103  36
68                                        Rheumatoid arthritis 05323    75  30
69                                      mTOR signaling pathway 04150    59  23
70                                        Pancreatic secretion 04972    85  34
71                        Retrograde endocannabinoid signaling 04723    96  37
72                                                Tuberculosis 05152   155  57
73                   Aldosterone-regulated sodium reabsorption 04960    37  16
74                         Complement and coagulation cascades 04610    66  26
75                                   Calcium signaling pathway 04020   167  59
76                Intestinal immune network for IgA production 04672    40  16
77                         Amyotrophic lateral sclerosis (ALS) 05014    50  21
78                                      GnRH signaling pathway 04912    88  34
79   Endocrine and other factor-regulated calcium reabsorption 04961    45  18
80                                              Bile secretion 04976    67  22
81                                              Thyroid cancer 05216    28  12
82  Epithelial cell signaling in Helicobacter pylori infection 05120    63  25
83                                  Osteoclast differentiation 04380   123  46
84                     Progesterone-mediated oocyte maturation 04914    77  29
85                   Natural killer cell mediated cytotoxicity 04650   121  38
86                                               Melanogenesis 04916    94  35
87                                        Dopaminergic synapse 04728   114  42
88                                          Mineral absorption 04978    46  15
89                                          Salivary secretion 04970    73  24
90                                                  Alcoholism 05034   145  47
91                                NF-kappa B signaling pathway 04064    82  29
92                                  Jak-STAT signaling pathway 04630   142  42
93                                      Long-term potentiation 04720    63  24
94                                             Prostate cancer 05215    86  32
95                                    Herpes simplex infection 05168   164  52
96                                   Vibrio cholerae infection 05110    49  17
97                                   Type II diabetes mellitus 04930    40  12
98                       Carbohydrate digestion and absorption 04973    35  11
99                                                      Asthma 05310    24   7
100                                          Pancreatic cancer 05212    67  24
101                  Chagas disease (American trypanosomiasis) 05142    95  34
102                                                     Glioma 05214    59  22
103                                              Leishmaniasis 05140    59  22
104                                          Cocaine addiction 05030    46  13
105                        NOD-like receptor signaling pathway 04621    54  20
106                                      Amphetamine addiction 05031    64  20
107                                             Oocyte meiosis 04114   102  35
108                       Toll-like receptor signaling pathway 04620    95  33
109                                   Chronic myeloid leukemia 05220    68  22
110                                        Allograft rejection 05330    31   8
111                                      p53 signaling pathway 04115    67  21
112                               Epstein-Barr virus infection 05169   181  59
113                                     Acute myeloid leukemia 05221    51  18
114                            Adipocytokine signaling pathway 04920    65  21
115                                    Regulation of autophagy 04140    32  11
116                                     Gastric acid secretion 04971    67  23
117                   Vasopressin-regulated water reabsorption 04962    43  15
118                      RIG-I-like receptor signaling pathway 04622    70  18
119                                 Autoimmune thyroid disease 05320    44  11
120                                   Type I diabetes mellitus 04940    37  11
121                                 TGF-beta signaling pathway 04350    73  24
122                                 Hedgehog signaling pathway 04340    49  16
123                                                    Measles 05162   128  32
124                                       Long-term depression 04730    58  18
125                                  Graft-versus-host disease 05332    33   7
126                                       Viral carcinogenesis 05203   179  54
127                    Neuroactive ligand-receptor interaction 04080   260  50
128                        Antigen processing and presentation 04612    62  15
129                                                 Cell cycle 04110   118  27
130                                         Taste transduction 04742    42   8
131                              Cytosolic DNA-sensing pathway 04623    59  13
132                       Maturity onset diabetes of the young 04950    20   4
133                                            RNA degradation 03018    64  14
134                                     Olfactory transduction 04740   102  14
135                                          Phototransduction 04744    24   3
136                                              RNA transport 03013   141  31
137                                     Fanconi anemia pathway 03460    46   1
            pNDE           tA    pPERT           pG        pGFdr       pGFWER
1   4.381365e-08 101.84838716 0.000005 6.604775e-12 9.048541e-10 9.048541e-10
2   2.807223e-11  -5.62714952 0.282000 2.102753e-10 1.440386e-08 2.880772e-08
3   2.632709e-06  26.07835730 0.000005 3.429573e-10 1.566172e-08 4.698515e-08
4   5.420283e-10 -11.31593175 0.061000 8.309768e-10 2.846096e-08 1.138438e-07
5   2.403222e-05  68.15576889 0.004000 1.649338e-06 4.519187e-05 2.259594e-04
6   3.370375e-06  -3.07547553 0.233000 1.182438e-05 2.671836e-04 1.619941e-03
7   1.501680e-05  -3.03562212 0.061000 1.365172e-05 2.671836e-04 1.870285e-03
8   1.087840e-05  12.08820845 0.171000 2.640531e-05 4.521909e-04 3.617528e-03
9   3.534791e-05 -11.47640962 0.229000 1.029991e-04 1.567875e-03 1.411087e-02
10  6.342459e-05  11.26416859 0.166000 1.311999e-04 1.797439e-03 1.797439e-02
11  4.119196e-05   8.39092912 0.519000 2.512656e-04 3.129398e-03 3.442338e-02
12  5.919072e-03  26.84578994 0.008000 5.188843e-04 5.923929e-03 7.108715e-02
13  2.676367e-02 -11.48880786 0.006000 1.563540e-03 1.647731e-02 2.142050e-01
14  4.358680e-04   2.30312703 0.836000 3.249335e-03 3.142734e-02 4.451589e-01
15  1.126631e-03  -6.49071103 0.345000 3.440950e-03 3.142734e-02 4.714101e-01
16  3.428106e-03  -1.18449965 0.161000 4.692521e-03 4.017971e-02 6.428754e-01
17  9.148611e-03  -8.41821229 0.078000 5.883706e-03 4.741575e-02 8.060677e-01
18  2.027165e-02  14.70041438 0.049000 7.861527e-03 5.983496e-02 1.000000e+00
19  4.319608e-02   8.71809441 0.028000 9.334309e-03 6.089511e-02 1.000000e+00
20  7.029292e-03 -10.19428261 0.173000 9.378475e-03 6.089511e-02 1.000000e+00
21  8.156605e-03 -17.60522073 0.155000 9.701099e-03 6.089511e-02 1.000000e+00
22  4.399731e-02  18.00376593 0.029000 9.778776e-03 6.089511e-02 1.000000e+00
23  8.740926e-03  -0.75310750 0.205000 1.312467e-02 7.817737e-02 1.000000e+00
24  3.225192e-03  -2.59311699 0.628000 1.458703e-02 8.326764e-02 1.000000e+00
25  8.281378e-03  -2.63020528 0.365000 2.055923e-02 1.009699e-01 1.000000e+00
26  1.230834e-02  12.47315238 0.257000 2.137138e-02 1.009699e-01 1.000000e+00
27  3.174325e-03   0.00000000 1.000000 2.143514e-02 1.009699e-01 1.000000e+00
28  2.091659e-02   1.31731308 0.152000 2.146388e-02 1.009699e-01 1.000000e+00
29  2.181614e-01   8.29865994 0.015000 2.199795e-02 1.009699e-01 1.000000e+00
30  5.486746e-01  15.18318180 0.006000 2.211020e-02 1.009699e-01 1.000000e+00
31  4.532188e-03  -1.51626444 0.842000 2.506617e-02 1.093509e-01 1.000000e+00
32  6.212885e-03   2.07570288 0.628000 2.554182e-02 1.093509e-01 1.000000e+00
33  1.406450e-02  -3.83270992 0.310000 2.805781e-02 1.164824e-01 1.000000e+00
34  1.780679e-02  10.84095790 0.275000 3.094408e-02 1.239768e-01 1.000000e+00
35  6.943784e-03  -2.30547515 0.725000 3.167290e-02 1.239768e-01 1.000000e+00
36  8.347825e-03   0.05344302 0.625000 3.263873e-02 1.242085e-01 1.000000e+00
37  8.711025e-03   4.57923053 0.636000 3.432562e-02 1.270976e-01 1.000000e+00
38  2.050101e-01  -3.23070984 0.030000 3.746306e-02 1.350642e-01 1.000000e+00
39  7.447330e-02  -2.74526504 0.093000 4.136543e-02 1.453093e-01 1.000000e+00
40  3.048123e-01  28.81009029 0.027000 4.773342e-02 1.634870e-01 1.000000e+00
41  3.804969e-01 -12.32368783 0.023000 5.022041e-02 1.671031e-01 1.000000e+00
42  2.891856e-02  -8.24498318 0.310000 5.122867e-02 1.671031e-01 1.000000e+00
43  1.894265e-02  -3.60482721 0.536000 5.675632e-02 1.808283e-01 1.000000e+00
44  1.828172e-01   6.39657371 0.066000 6.536563e-02 2.035248e-01 1.000000e+00
45  5.964061e-01  -4.02662204 0.022000 6.998111e-02 2.123799e-01 1.000000e+00
46  2.098190e-01 -16.21289908 0.064000 7.131002e-02 2.123799e-01 1.000000e+00
47  1.725653e-02   2.25309644 0.822000 7.454970e-02 2.144953e-01 1.000000e+00
48  1.646722e-01 -11.24083209 0.087000 7.515164e-02 2.144953e-01 1.000000e+00
49  1.828172e-01  -3.99124711 0.084000 7.948918e-02 2.196180e-01 1.000000e+00
50  1.449619e-01 -13.21262891 0.110000 8.193850e-02 2.196180e-01 1.000000e+00
51  6.304584e-02 -18.48063141 0.254000 8.221908e-02 2.196180e-01 1.000000e+00
52  3.039152e-02   0.65995023 0.536000 8.335866e-02 2.196180e-01 1.000000e+00
53  1.933837e-02  -1.37689631 0.900000 8.791073e-02 2.272410e-01 1.000000e+00
54  2.777386e-01  16.11183473 0.077000 1.036151e-01 2.520565e-01 1.000000e+00
55  1.277725e-01 -11.44050452 0.168000 1.039222e-01 2.520565e-01 1.000000e+00
56  3.486546e-02   2.56928074 0.624000 1.050352e-01 2.520565e-01 1.000000e+00
57  6.622114e-02   9.46857992 0.332000 1.059120e-01 2.520565e-01 1.000000e+00
58  2.255562e-02  -0.09633095 0.984000 1.067101e-01 2.520565e-01 1.000000e+00
59  7.207796e-02  -3.58077636 0.318000 1.094631e-01 2.525022e-01 1.000000e+00
60  3.251880e-02  -2.20290858 0.714000 1.105849e-01 2.525022e-01 1.000000e+00
61  1.805481e-01   6.07788264 0.144000 1.208872e-01 2.682411e-01 1.000000e+00
62  3.227434e-01  23.68766196 0.082000 1.225839e-01 2.682411e-01 1.000000e+00
63  4.500430e-02   1.63658774 0.599000 1.243685e-01 2.682411e-01 1.000000e+00
64  2.777386e-01 -14.70231162 0.098000 1.253097e-01 2.682411e-01 1.000000e+00
65  3.192130e-02   0.03385799 0.988000 1.405519e-01 2.962401e-01 1.000000e+00
66  1.846189e-01  -6.41340954 0.175000 1.432043e-01 2.972574e-01 1.000000e+00
67  1.953049e-01  -6.45172459 0.171000 1.469235e-01 3.004257e-01 1.000000e+00
68  5.230426e-02   0.57595950 0.665000 1.516039e-01 3.054372e-01 1.000000e+00
69  1.055994e-01   2.22226268 0.353000 1.598938e-01 3.172051e-01 1.000000e+00
70  4.079748e-02  -0.10782320 0.930000 1.620756e-01 3.172051e-01 1.000000e+00
71  5.880097e-02   0.42579029 0.701000 1.726620e-01 3.331647e-01 1.000000e+00
72  5.773095e-02  -3.80120057 0.739000 1.772407e-01 3.372496e-01 1.000000e+00
73  7.065352e-02   1.17413454 0.640000 1.852255e-01 3.476149e-01 1.000000e+00
74  7.989157e-02   6.74069299 0.578000 1.881849e-01 3.483964e-01 1.000000e+00
75  1.067456e-01   5.60908981 0.460000 1.970913e-01 3.555538e-01 1.000000e+00
76  1.321313e-01   1.15772022 0.372000 1.972415e-01 3.555538e-01 1.000000e+00
77  5.769591e-02  -0.48086493 0.884000 2.027819e-01 3.607937e-01 1.000000e+00
78  6.572977e-02   3.07849463 0.800000 2.074614e-01 3.638656e-01 1.000000e+00
79  1.148103e-01   2.70513911 0.465000 2.098203e-01 3.638656e-01 1.000000e+00
80  3.891848e-01  -2.38649861 0.145000 2.186575e-01 3.706565e-01 1.000000e+00
81  1.159882e-01  -2.41956732 0.488000 2.191473e-01 3.706565e-01 1.000000e+00
82  7.840352e-02  -1.26914330 0.774000 2.307260e-01 3.854813e-01 1.000000e+00
83  6.304584e-02  -0.01117285 0.996000 2.366003e-01 3.905330e-01 1.000000e+00
84  1.115996e-01   2.42089218 0.610000 2.510045e-01 4.067792e-01 1.000000e+00
85  4.572590e-01  27.65095094 0.150000 2.523813e-01 4.067792e-01 1.000000e+00
86  1.002517e-01   6.35348074 0.710000 2.592729e-01 4.097510e-01 1.000000e+00
87  9.000481e-02   1.09042349 0.803000 2.621585e-01 4.097510e-01 1.000000e+00
88  4.377701e-01  -0.65973927 0.166000 2.631977e-01 4.097510e-01 1.000000e+00
89  3.778385e-01   3.37468408 0.197000 2.678023e-01 4.122350e-01 1.000000e+00
90  3.459981e-01 -12.62095459 0.231000 2.818703e-01 4.290692e-01 1.000000e+00
91  2.048582e-01   4.84388093 0.430000 3.020932e-01 4.547996e-01 1.000000e+00
92  6.350831e-01  -3.63122401 0.145000 3.117166e-01 4.641867e-01 1.000000e+00
93  1.245843e-01   2.22826563 0.818000 3.346383e-01 4.929618e-01 1.000000e+00
94  1.129788e-01   0.28715209 0.976000 3.533900e-01 5.122659e-01 1.000000e+00
95  4.069566e-01  -7.61338417 0.273000 3.552209e-01 5.122659e-01 1.000000e+00
96  3.144623e-01  -1.31227639 0.360000 3.598314e-01 5.135094e-01 1.000000e+00
97  5.917208e-01  -5.56657518 0.205000 3.771868e-01 5.327277e-01 1.000000e+00
98  5.209139e-01   1.50686941 0.257000 4.030771e-01 5.634854e-01 1.000000e+00
99  6.356783e-01   0.28758650 0.218000 4.124525e-01 5.707676e-01 1.000000e+00
100 2.109464e-01   2.36933932 0.689000 4.256583e-01 5.831518e-01 1.000000e+00
101 1.609869e-01  -0.27207798 0.976000 4.479150e-01 6.025822e-01 1.000000e+00
102 1.642482e-01   0.43104257 0.959000 4.486378e-01 6.025822e-01 1.000000e+00
103 1.642482e-01   0.09930081 0.978000 4.543750e-01 6.043628e-01 1.000000e+00
104 6.871654e-01   3.43640782 0.242000 4.646251e-01 6.117475e-01 1.000000e+00
105 1.880297e-01  -0.72763331 0.897000 4.688576e-01 6.117475e-01 1.000000e+00
106 5.017793e-01  -3.19401563 0.390000 5.149105e-01 6.654976e-01 1.000000e+00
107 2.369688e-01  -1.48418935 0.842000 5.211270e-01 6.672374e-01 1.000000e+00
108 2.199553e-01   0.69811871 0.926000 5.277745e-01 6.694917e-01 1.000000e+00
109 4.209611e-01  -3.73548169 0.495000 5.351948e-01 6.726760e-01 1.000000e+00
110 7.772559e-01   0.61993196 0.284000 5.542283e-01 6.852399e-01 1.000000e+00
111 4.930528e-01  -2.22690188 0.449000 5.551943e-01 6.852399e-01 1.000000e+00
112 3.037783e-01  -1.59540434 0.762000 5.701945e-01 6.974700e-01 1.000000e+00
113 2.777386e-01  -0.52848806 0.865000 5.828559e-01 7.066483e-01 1.000000e+00
114 4.278063e-01   1.92816998 0.575000 5.909803e-01 7.102132e-01 1.000000e+00
115 3.840534e-01  -1.52731147 0.704000 6.240089e-01 7.302655e-01 1.000000e+00
116 2.934654e-01  -0.30596048 0.925000 6.254218e-01 7.302655e-01 1.000000e+00
117 3.221160e-01  -0.40404478 0.860000 6.326207e-01 7.302655e-01 1.000000e+00
118 8.458926e-01  -3.28242503 0.329000 6.342595e-01 7.302655e-01 1.000000e+00
119 8.337946e-01   0.61993196 0.341000 6.419014e-01 7.302655e-01 1.000000e+00
120 6.067469e-01   0.33234546 0.470000 6.429655e-01 7.302655e-01 1.000000e+00
121 3.778385e-01   2.06682129 0.759000 6.449790e-01 7.302655e-01 1.000000e+00
122 4.297205e-01  -1.59875398 0.703000 6.637051e-01 7.453082e-01 1.000000e+00
123 9.321150e-01  -4.88903646 0.349000 6.906235e-01 7.656455e-01 1.000000e+00
124 5.205474e-01  -2.86729237 0.629000 6.929930e-01 7.656455e-01 1.000000e+00
125 9.173300e-01   0.33234546 0.376000 7.120634e-01 7.804215e-01 1.000000e+00
126 5.778484e-01   0.33707133 0.732000 7.869292e-01 8.556293e-01 1.000000e+00
127 9.999891e-01  -0.67121961 0.637000 9.242747e-01 9.968355e-01 1.000000e+00
128 8.934756e-01  -0.52262510 0.731000 9.313500e-01 9.968355e-01 1.000000e+00
129 9.753818e-01   2.32836055 0.700000 9.433121e-01 1.000000e+00 1.000000e+00
130 9.684795e-01   1.05189602 0.751000 9.588931e-01 1.000000e+00 1.000000e+00
131 9.457099e-01  -0.30980084 0.885000 9.859201e-01 1.000000e+00 1.000000e+00
132 9.030075e-01   0.00000000 1.000000 9.951363e-01 1.000000e+00 1.000000e+00
133 9.545407e-01   0.00000000 1.000000 9.989507e-01 1.000000e+00 1.000000e+00
134 9.999794e-01  -0.09096534 0.982000 9.998367e-01 1.000000e+00 1.000000e+00
135 9.898599e-01   0.00000000 1.000000 9.999484e-01 1.000000e+00 1.000000e+00
136 9.913878e-01   0.00000000 1.000000 9.999628e-01 1.000000e+00 1.000000e+00
137 1.000000e+00   0.00000000 1.000000 1.000000e+00 1.000000e+00 1.000000e+00
       Status
1   Activated
2   Inhibited
3   Activated
4   Inhibited
5   Activated
6   Inhib