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Table 5 Upstream regulator analysis with IPA: predicted activated regulators

From: Transfection of Sertoli cells with androgen receptor alters gene expression without androgen stimulation

IPA–prediction

Micro array analysis

Upstream regulator

Molecule type

z-score

FDR

FC

Mean AR17

Mean noAR

Regulation AR17 [level]

Ahr

Ligand-dependent nuclear receptor

3.185

0.895

−1.017

−1.219

−1.194

 

Bmp6

Growth factor

2.791

0.011

−1.483

2.595

3.164

 

Ccl5

Cytokine

2.190

0.016

2.529

2.922

1.583

[Up L3]

Ddx58

Enzyme

2.789

0.019

2.096

3.316

2.249

[Up L3]

Dock8

Other

2.530

0.010

−1.656

2.545

3.272

[Down L2]

Egf

Growth factor

2.539

 

<not measured>

  

Erk:

Group of kinases (n=7)

2.372

  

<group>

  

Mapk1

Kinase

 

0.009

−1.019

3.670

3.697

 

Mapk3

Kinase

 

0.027

−1.280

5.646

6.002

 

Mapk4

Kinase

 

0.701

1.086

−2.321

−2.440

 

Mapk6

Kinase

 

0.037

1.131

5.152

4.975

 

Mapk7

Kinase

 

0.758

−1.047

2.862

2.928

 

Mapk12

Kinase

 

0.018

−2.005

0.121

1.125

[Down L3]

Mapk15

Kinase

 

0.208

1.217

0.507

0.224

 

Mek:

Group of kinases (n=7)

2.942

  

<group>

  

Map2k1

Kinase

 

0.105

1.182

4.651

4.410

 

Map2k2

Kinase

 

0.177

1.090

4.816

4.691

 

Map2k3

Kinase

 

−1.066

−0.092

4.360

4.452

 

Map2k4

Kinase

 

1.023

0.032

3.336

3.303

 

Map2k5

Kinase

 

−1.058

−0.082

3.327

3.408

 

Map2k6

Kinase

 

1.177

0.235

3.760

3.525

 

Map2k7

Kinase

 

−1.125

−0.170

−1.445

−1.275

 

P38 Mapk:

Group of kinases (n= 5)

2.624

  

<group>

  

Mapk1

Kinase

 

0.009

−1.019

3.670

3.697

 

Mapk11

Kinase

 

0.087

−1.343

0.139

0.565

 

Mapk12

Kinase

  

<see above>

  

Mapk13

Kinase

  

<not measured>

  

Mapk14

Kinase

 

0.046

−1.276

3.242

3.594

 

Mapk2/1: group of

Kinases (n= 2)

2.401

  

<group>

  

Map2k1

Kinase

  

<see above>

  

Map2k2

Kinase

  

<see above>

  

F7

Peptidase

2.592

 

<not measured>

  

Fgf2

Growth factor

2.085

0.122

1.178

0.417

0.180

 

Fos

Transcription regulator

2.086

0.069

−1.425

2.972

3.482

 

Hras

Enzyme

3.258

 

<not measured>

  

Ifn / Ifn alpha:

Group of groups

      

Ifn:

Group of cytokines

2.429

  

<group>

  

Ifn alpha:

Group of cytokines

2.228

  

<group>

  

Ifna1

Cytokine

 

0.104

1.306

2.728

2.343

 

Ifna2

Cytokine

2.448

 

<not measured>

  

Ifna4

Cytokine

2.236

 

<not measured>

  

Ifna5 - 8

cyTokine (n=4)

  

<not measured>

  

Ifna10, 13, 14, 16, 17, 21

Cytokine (n=6)

  

<not measured>

  

Ifnk

Cytokine

  

<not measured>

  

Ifnw1

Cytokine

  

<not measured>

  

Ifnz

Cytokine

  

<not measured>

  

Ifn beta:

Group of cytokines (n=2)

2.767

     

Ifnb1

Cytokine

2.591

0.079

2.953

−1.949

−3.511

 

Il6

Cytokine

2.443

0.014

1.481

−0.730

−1.296

 

Ifnar:

Group of transmembrane receptors

2.749

  

<group>

  

Ifnar1

Transmembrane receptor

  

<not measured>

  

Ifnar2

Transmembrane receptor

  

<not measured>

  

Ifne

Cytokine

2.219

 

 <not measured>

  

Ifng

Cytokine

2.811

 

<not measured>

  

Ifnl1

Cytokine

2.764

 

<not measured>

  

Igf2

Growth factor

2.213

0.001

−9.285

1.909

5.124

[Down L1]

Ikbke

Kinase

2.090

0.013

−2.034

−1.262

−0.238

[Down L3]

Il1: group of

Cytokines (n=11)

2.207

     

Il1b

Cytokine

  

<not measured>

  

Il18

Cytokine

2.372

0.300

−1.056

0.531

0.610

 

Il1f10

Cytokine

 

0.689

1.102

−2.284

−2.424

 

Il1rn

Cytokine

 

0.009

1.812

0.062

−0.796

[Up L2]

Il33

Cytokine

 

0.001

10.690

1.998

−1.420

[Up L1]

Il17a

Cytokine

  

<not measured>

  

Il36a

Cytokine

  

<not measured>

  

Il36b

Cytokine

  

<not measured>

  

Il36g

Cytokine

  

<not measured>

  

Il36rn

Cytokine

 

0.019

1.393

2.076

1.598

 

Il37

Cytokine

  

<not measured>

  

Irf3

Transcription regulator

3.157

0.520

1.336

3.450

3.033

 

Irf5

Transcription regulator

2.934

0.113

1.096

1.321

1.188

 

Irf7

Transcription regulator

3.901

0.003

5.540

5.574

3.104

[Up L1]

Kras

Enzyme

2.616

0.191

−1.097

3.119

3.253

 

Lh [Cga, Lhb]

Complex

2.012

     

Lhb

Other

 

0.480

1.044

2.593

2.530

 

Cga

Other

 

0.251

1.273

−0.193

−0.541

 

Map3k7

Kinase

2.375

0.352

−1.067

4.577

4.671

 

Mavs

Other

2.630

0.021

−1.231

2.569

2.868

 

Pdgf bb

Complex

3.491

  

<group>

  

Pdgfb

Growth factor

  

1.156

2.037

1.828

 

Pdlim2

Other

2.324

0.003

1.346

3.226

2.798

 

Samsn1

Other

2.309

 

<not measured>

  

Sash1

Other

2.530

 

<not measured>

  

Sphk1

Kinase

2.172

0.611

1.237

−0.033

−0.341

 

Src

Kinase

2.158

0.033

1.348

3.704

3.273

 

Stat1

Transcription regulator

2.194

0.013

1.375

3.163

2.703

 

Stat2

Transcription regulator

2.173

0.535

1.067

3.865

3.772

 

Tac1

Other

2.153

0.910

1.055

−2.385

−2.462

 

Tgfa

Growth factor

2.165

0.586

1.088

2.152

2.031

 

Ticam1

Other

2.702

0.574

−1.035

3.646

3.696

 

Tlr3

Transmembrane receptor

3.633

0.049

−1.414

−0.244

0.256

 

Tlr4

Transmembrane receptor

3.175

 

<not measured>

  

Tlr9

Transmembrane receptor

3.645

0.249

1.134

2.534

2.353

 

Tnfsf11

Cytokine

2.168

0.539

1.115

−0.643

−0.800

 
  1. Z-score < 2.0
  2. Based on gene expression patterns, predictions are made on activation or inactivation of known upstream regulators. Absolute activation z-scores of higher than 2.0 are considered to be highly significant. We found more than twice as much regulators predicted to be activated as compared to inhibited. These tables show the predicted upstream regulators with an absolute z-score above 2.0 in detail—some are in fact complexes or groups. The prediction is opposed to the real measurement on the micro array (rightmost columns), as far as the respective genes have passed QC and is otherwise marked as “not measured”. Mean expression per group is given as logarithm of the intensity to base 2. Reasonably high expression values are in bold face. The column “regulation AR17” denotes if the respective gene is contained in the set of regulated genes (level = L1) or at least close to significance (level = L2/L3) which holds true for the minority of genes. Activation or inhibition is not necessarily reflected by significant change of gene expression, since processes not measurable on a micro array, like for example phosphorylation, are more likely to be responsible for that