Androgen Receptor and FoxA1 Interaction Studyresearch.med.helsinki.fi/sysbio/csb/FOXA1.pdf · 15...

Androgen Receptor and FoxA1 Interaction Study

Marko Laakso Biswajyoti Sahu Kristian Ovaska Olli A. Jänne Sampsa Hautaniemi

July 10, 2011

Abstract

This Anduril analysis compares androgen receptor (AR) and FoxA1 binding sites in LNCaP-1F5 prostate cancer cells.Binding site data have been integrated with expression profiles obtained for the DHT stimulus.

This document is generated automatically by Anduril (Engine 1.2.2).

Contents

1 Expression analysis for AR 5

2 Summary of DEGs in AR 6

3 List of differentially expressed genes 6

3.1 Gene set: fcC fcOver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

3.2 Gene set: fcC fcUnder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

3.3 Gene set: fcA1 fcOver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

3.4 Gene set: fcA1 fcUnder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

3.5 Gene set: fcE fcOver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

3.6 Gene set: fcE fcUnder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4 Expression analysis for GR 9

5 Summary of DEGs in GR 9

6 List of differentially expressed genes 9

6.1 Gene set: fcsiCx fcOver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

6.2 Gene set: fcsiCx fcUnder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

6.3 Gene set: fcsiFx fcOver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

6.4 Gene set: fcsiFx fcUnder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

7 Gene set overlaps 14

8 Gene set comparison 17

9 Candidate report for Unique DEGs for AR 19

9.1 Moksiskaan candidate pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

9.1.1 GO enrichment of the candidate pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

9.2 Candidate genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

9.2.1 GO enrichment of all candidates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

10 Candidate report for Unique DEGs for AR with siFOXA1 36



10.2 Candidate genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41


11 Candidate report for Common DEGs for AR and siFOXA1 56



11.2 Candidate genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66


2

12 ChIP-seq peaks 73

12.1 AR DHT binding sites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

12.2 FoxA1 binding sites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

12.3 AR binding sites (siFOXA1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

12.4 FoxA1 binding sites (siFOXA1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

12.5 AR and FoxA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

12.6 AR and FoxA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

12.7 AR and FoxA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

12.8 AR without FoxA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

12.9 AR without FoxA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

12.10AR without FoxA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

12.11FoxA1 without AR binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

12.12FoxA1 without AR binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

12.13FoxA1 without AR binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

12.14AR and FoxA1 siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

12.15AR and FoxA1 siFOXA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

12.16AR and FoxA1 siFOXA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

12.17AR without FoxA1 siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

12.18AR without FoxA1 siFOXA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

12.19AR without FoxA1 siFOXA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

12.20FoxA1 without AR siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

12.21FoxA1 without AR siFOXA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

12.22FoxA1 without AR siFOXA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

12.23AR and AR siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

12.24AR and AR siFOXA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

12.25AR and AR siFOXA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

12.26AR without AR siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

12.27AR without AR siFOXA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

12.28AR without AR siFOXA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

12.29AR siFOXA1 without AR binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132

12.30AR siFOXA1 without AR binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

12.31AR siFOXA1 without AR binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

12.32FoxA1 and FoxA1 siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

12.33FoxA1 and FoxA1 siFOXA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141

12.34FoxA1 and FoxA1 siFOXA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

12.35FoxA1 without FoxA1 siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

12.36FoxA1 without FoxA1 siFOXA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

12.37FoxA1 without FoxA1 siFOXA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

12.38FoxA1 siFOXA1 without FoxA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

12.39FoxA1 siFOXA1 without FoxA1 binding site overlaps (up) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

12.40FoxA1 siFOXA1 without FoxA1 binding site overlaps (down) . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

3

12.41AR and FoxA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

12.42AR without FoxA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159

12.43FoxA1 without AR binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

12.44AR and AR siFOXA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163

12.45AR without AR siFOXA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165

12.46AR siFOXA1 without AR binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167

12.47FoxA1 and FoxA1 siFOXA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170

12.48FoxA1 without FoxA1 siFOXA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

12.49FoxA1 siFOXA1 without FoxA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

12.50AR and FoxA1 siFOXA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176

12.51AR without FoxA1 siFOXA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

12.52FoxA1 without AR siFOXA1 binding site overlaps (stable) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181

12.53GR DEX binding sites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183

12.54GR DEX binding sites (siFOXA1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185

12.55GR and GR siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188

12.56GR without GR siFOXA1 binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190

12.57GR siFOXA1 without GR binding site overlaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192

12.58AR and FOXA1 overlaps unique for AR parental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

13 AR versus AR siFOXA1 197

14 Expression comparision 199

14.1 Box plots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200

15 System configuration 213

4

1 Expression analysis for AR

Group Definition Descriptionce median(ce1, ce2) AR controls for FoxA1 studycd median(cd1, cd2) AR cases (DHT) for FoxA1 studya1e median(a1e1, a1e2) siFOXA1 controlsa1d median(a1d1, a1d2) siFOXA1 casesfcC ratio(cd/ce) AR DHT samples divided by their controlsfcA1 ratio(a1d/a1e) siFOXA1 DHT samples divided by their controlsfcE ratio(ce/a1e) siFOXA1 samples divided by the parental cells

Table 1: Sample groups

ce (median)

fcC (ratio)

fcE (ratio)

cd (median)

a1e (median)

fcA1 (ratio)

a1d (median)

ce1

ce2

cd1

cd2

a 1 e 1

a 1 e 2

a 1 d 1

a 1 d 2

5

2 Summary of DEGs in AR

Gene set SizefcC fcOver 195fcC fcUnder 106fcA1 fcOver 242fcA1 fcUnder 175fcE fcOver 188fcE fcUnder 199

3 List of differentially expressed genes

Overexpressed genes are sorted with the most overexpressed first and underexpressed genes with the most underexpressed

first. Genes go by the column first and then by row.

3.1 Gene set: fcC fcOver

Number of genes: 195

PHGR1 C1orf116 LPAR3 ATAD2 PYGB HSD17B11 RP11-546D6.2 SMPD2FKBP5 SPDEF HES1 PPFIBP2 PAQR4 AC068353.1 CAMKK2 PTGER4PGC DBI KLK3 JAG1 ACAD8 AL121833.1 MKLN1 MRPS18ASLC45A3 MBOAT2 NBL1 ELOVL2 HIVEP1 GDF15 VWF HMG20BS100P STK39 CEBPD BRP44 APP WDYHV1 CEBPG TNS3NCAPD3 EXTL2 CNTNAP2 SLC2A12 SHROOM3 MTOR VIPR1 BMPR1BSAT1 PECI TMPRSS2 RP11-312J18.5 DHCR24 CTD-2048F20.1 CORO1B TACC2MICAL1 TUBA3D TBC1D4 KLK2 HEBP2 ZBTB24 STRA13 TIPARPTSKU ZMIZ1 CTD-2653M23.1 DNAJB9 ABHD3 SGK1 CBLL1 MERTKPMEPA1 KRT8 MLPH PFKFB2 KIF22 TEX2 GLRX SETBP1ST6GALNAC1 TRPM8 C9orf152 PRKCH MAPK6 REPS2 C15orf23 SEMA4AALDH1A3 TM4SF1 ISG20 SMS CRIP2 AC020915.4 UGT2B28 SEPP1CLDN8 RP11-529H2.2 HOMER2 CENPN HERC5 ATP1A1 RAB3IP UBE2G1SORD NFKBIA FAM43A TRPM4 AL162497.1 SNORD88C PTPRCAP YIPF1ST3GAL4 ERRFI1 PEA15 RIPK4 IRS2 BTG1 ACACA TACSTD2ELL2P1 C1orf21 ELOVL5 VPS26B ACSL3 MAP7D1 MPZL1 AF127936.7ELL2 CREB3L4 SLC43A1 ADAMTS1 APOD COBLL1 HSD17B4 C3orf25SOCS2 RAB3B EAF2 BCAP29 EML1 TBC1D8 DNM1L SPATA2SLC41A1 TMEFF2 SLC35F2 PRR15L KCNN2 FADS2 PLEKHF1 GTF3C6ODC1 TMEM79 GNMT C4orf34 CYP11A1 UGDH SUN2 C12orf44ABCC4 WWC1 GPT2 GUCY1A3 HPGD LONRF1 PPAPDC1BAC061975.8 LRIG1 MYBPC1 PDIA5 C3orf58 TRIB3 ABCC1RGS2 FAM174B DNASE2B ANKRD37 GLRX2 ARID5B INPP4BNDRG1 CAP2 PPAP2A LIMCH1 C17orf48 IDH1 ADRB2LCP1 ZBTB16 SASH1 CAPZB UAP1 MPHOSPH9 KCNMA1

3.2 Gene set: fcC fcUnder


CBLN2 NIPSNAP3A GALNTL4 GCG TRIB1 C6orf192 TSPAN3 C1orf53FAM198B BCHE KIF5B FFAR2 SELENBP1 IL27RA TMEM14A CYBASC3LRRN1 DDC DEGS2 SOX9 FAM47E RP11-510N19.5 HCP5 IRX3UGT2B17 CAMK2N1 AC100826.1 GAS6 STBD1 ADORA2B HCP5 MAPKAPK3CXCR7 REXO2 CALD1 NETO1 FAM113B ZNF462 HCP5 INSIG2COLEC12 RP11-181C21.4 TSPAN8 CDH26 MAPK1IP1L SLC30A3 HCP5 PNMA3LMO4 SLITRK3 BAMBI MT1X FIGNL1 TULP4 ZMYND15 TMEM123CNKSR3 ATP1B1 SLC44A1 ANKRD16 RNFT2 TGM3 SRSF7 ELOVL6TMEM144 RASL11B REEP1 NUCB2 PRKD1 MT1A DIO1ACPP ST7 GLDC ZNF503 PRSS1 C6orf64 NAP1L3GOLIM4 AC010170.1 TOX2 CCDC28B TSHZ3 POLR3GL C20orf177ATP12A TMEM158 LGMN FZD2 CDK8 GPER HOXC13SERPINI1 C5orf30 WNT5A COL16A1 CITED2 ZIC2 RP11-611D20.2C11orf92 SDC4 PITX1 C5orf13 TNFRSF21 NAB1 P2RX4

3.3 Gene set: fcA1 fcOver


6

FKBP5 MBOAT2 TSKU TACC1 C16orf93 Z82214.1 FSTL1 DLG5PGC TBC1D8 FOXO1 SLC43A1 CTD-2653M23.1 DHCR24 AC068353.1 CDC25ACRISPLD2 SLC16A6 KLF9 MICAL1 SHROOM3 FZD8 CTD-2048F20.1 ARHGAP44TIPARP EDN2 PMEPA1 KRT8 SAT1 MAP7D1 OLAH ST3GAL5ACTA2 ZNF589 SORD C7orf63 SH3PXD2B ABCC8 CTDSPL DCXRSNAI2 CAMP ATAD2 CLDN8 TMEM14C PEA15 TAX1BP3 SHC1AP1S2 RHOB HIST1H4H NDRG1 TPM1 ZSWIM6 PIK3CD KIAA0040ITPR3 FADS1 KLF15 UAP1 DNASE2B CD68 ARRDC1 ADAM9SGK1 ACPL2 C15orf23 GALNTL4 TPD52L1 PIK3C2A TSPAN13 RAP2ACAP2 IRX3 ZDHHC8P1 BRP44 KLK3 SSR3 GSTM3 PHKA1ST3GAL4 ODC1 PACSIN1 C12orf44 SLC35F2 LCP1 AUTS2 PTGER4HOMER2 LDLRAD3 C3orf58 HARS FADS2 TMEM100 AC073873.1 DHCR7CEBPD JUN RBBP7 STK39 PLCXD1 SUN2 RGS4 GUCY1A3SPDEF AL162497.1 KCNMA1 WDR41 ZMIZ1 IL6R IL18R1 CCDC17ALDH1A3 IRS2 JAG1 TSC22D1 STEAP2 NPPC PRPS2 KRT19ELOVL5 CDKN1C USP10 MKLN1 PHLDA2 GLUD1 BCAP29 STEAP1ITPRIP PAK1IP1 CTGF EEF2K RHBDF1 KIF22 CEP70 RP11-529H2.2CITED1 TMPRSS2 S100P CD24P4 TMEFF2 PTPN1 CREB3L4 CR759786.11ERRFI1 EVL GLRX PLXNB1 CCND3 SLC5A6 HS1BP3 AL844527.3CYR61 SERPINA3 AL590369.1 PPAP2A GNMT NFIL3 CRK CR759817.7MPZL2 C1orf116 PTGES MYBPC1 FSIP1 GBE1 COBLL1 AL662827.4PLEKHF1 ATP1A1 AC061975.8 FAM107B WHAMM KRTAP13-2 RIT1 B3GALT4ELOVL2 ETS2 EZR ETNK2 CLDN12 ACAA1 ANXA5 CRNDENUDT11 DUSP1 C6orf52 SLC44A3 IRX5 LACTB2 PTPRCAP KRT16SYBU MPZL1 KLK2 RNF24 ABHD3 FAM8A1 CBLL1 C17orf91SLCO2A1 TUBA3D ALDH3A2 TSC22D3 PPM1H PARP4 NCAPD3UGDH C9orf152 C11orf75 OBFC2A VCL F2RL1 HIST2H2BESOCS2 PGF S100A10 C4orf34 RBM24 TM4SF1 AL662827.3ELL2P1 PIAS1 NET1 TGFBR2 HES1 CDC42EP4 CR759817.9ELL2 WIPI1 C1orf21 REN MAK GK5 CR759786.5SLC45A3 NFKBIA CAPN2 PYGB TTLL12 TMEM149 BX000343.1

3.4 Gene set: fcA1 fcUnder


AC010170.1 LRRN1 ZG16B FAM111A PHLDA1 KAZALD1 FHOD1 NIPSNAP3ATMEM158 NAP1L3 RP11-510N19.5 PRKD1 C7orf23 CDR2L METRN LIMA1COLEC12 SERPINI1 SIPA1L2 MMP15 PLEKHG4 BARD1 CFD TSPAN9DEPTOR LMO4 MATN2 CCDC28B ATP12A TMEM144 GC LIN7APIK3IP1 C6orf192 CBLN2 HBQ1 TSPAN7 Z83851.1 ADORA2B NUAK2TNFRSF21 ENPP4 CNKSR3 AMOT POLB PROM2 TRIB1 NCRNA00245YPEL2 RP11-181C21.4 MT1F REXO2 TMEM123 MUC13 NDUFS2 TP53INP1MT1A TSPAN8 TRIM45 GAL PDE2A ILDR1 KLF13 CGNL1SLITRK3 TSPAN15 OAF IGFBP2 ENPP5 FHOD3 NCOR2 NTPCRADRA2C VASN PIM1 SLC16A10 SRSF7 LRBA RASL11B MYT1ASS1 C1orf115 HSD11B2 ALDH3B2 CCDC14 FOLH1 FFAR2 COL17A1BTG2 ZNF503 GLDC TMEM51 SHROOM1 B4GALNT4 SLC27A2 STAMBPL1BAMBI LGALS4 NUP54 LRRC26 P2RX4 LGALS3BP ELF3 ANKRD43BCHE ALDH4A1 HSD3B7 C11orf52 PPP1R14B ZNF239 AP3M2 AIDAHS3ST1 ODAM DDC DPYSL2 TSPAN1 MAPKAPK3 PDGFRL RSL24D1CAMK2N1 SLPI ELOVL6 MT1X LINGO1 KLHDC5 OGDHL GRAMD4PPP2R2A LRRTM4 TMEM116 SUSD4 PYGL CSPG5 ANXA9 SPTBN5FAM47E SEMA3F RARRES3 ALCAM PLXDC2 HDDC3 POLR3GL IL17CSTBD1 CMBL F12 GATA2 CGN FYCO1 TLCD1 RCOR2GOLIM4 AIF1L RAI14 CYP2J2 HIBADH ACPP CCNG2 ALG13EXOG IRF1 HOXC13 CHTF18 TANC1 MAL2 MYO6 FKBP1ACBLB SLC20A1 MOSC2 GFOD1 CYFIP2 CA11 NCAM2

3.5 Gene set: fcE fcOver


ACPP TMEM144 RRM2 PRUNE2 AL935042.3 SLC44A4 CR933877.1 TMEM42DDC SLC45A3 RRM2P3 CENPM CR759798.5 ARHGEF26 WDR54 RASL11BUGT2B17 C1orf116 MELK AMACR BX908719.2 NUP93 KIAA0101 VPS37CHMGCS2 RWDD2A ERGIC1 TSPAN3 CR936913.3 AC004381.6 GRB10 TUBA1CAL589734.1 TNFRSF19 GINS2 TJP1 BX088556.5 CCNB2 PIGQ CENPFSPON2 UGT2B7 LGMN KIF20A AL662845.2 TMEM170A SUV39H1 SMYD2AC100826.1 CDC45 STEAP2 ENSA HLA-DMB ZCCHC24 CAP2 NIPSNAP3AHES6 GCG PRC1 GLDC POLA2 OIP5 ZMYND12 LPCAT1FAM198B TOP2A PBK REEP1 FANCE STEAP1 CHEK1 MCM5CNKSR3 RAP1GAP C6orf64 PLEKHH1 FZD2 CTXN1 C16orf75 RFC3TMEFF2 SLC2A12 MAP7D1 DEGS1 AL391319.1 AP2S1 C12orf75 DIO1TFF3 ST7 FGFRL1 NONO SMOC2 RDH11 TMEM14A NUSAP1

7

SPDEF TMSB15A MCM2 FIGNL1 MCM4 TM4SF1 POC1A CTSL2CALD1 FOXA1 ANKRD16 BX088650.6 RAD51AP1 BAAT1 AC063976.6 NCRNA00287C7orf63 TYMS ARL2 BX248088.1 KIF5B PASK P4HA2 MBCDCA5 ZIC2 BCL9 KIFC1 C5orf30 PLDN KIF2C KCNK5RP11-45B20.3 C9orf152 APOD CTSF OSBPL5 BBS4 DLGAP5 SMUG1GZMH HIST1H4C KBTBD11 PNPLA6 AC099759.1 SLC22A23 RPS6KA4 MCL1TRIM68 TMPRSS2 COBL BCAT2 AL662834.7 EML3 CDH26 FAM64AMIPEP FAM83D UGT2B11 C1orf85 CR936237.3 CLDN12 TIMELESS SORDMAST4 RAMP1 TOX2 ASF1B CR388202.1 TRIB1 ST3GAL1TK1 GNG5 CDC20 AC010296.1 AL844853.11 AURKB FZD9AMHR2 MIR25 IGF2R SEMA6A BX005460.2 UBE2T CCNA2TGM3 MIR93 NCAPG CR752645.1 CR759784.2 PITX1 MCM6

3.6 Gene set: fcE fcUnder


SLPI MOSC1 MT1A NUPR1 FTH1P3 HIBCH TMEM47 YAP1IGFBP3 S1PR3 THRSP SIPA1L2 NFKBIZ CITED2 CCDC85A VASNGDE1 TMEM100 C13orf15 TBC1D8 CDKN1C SLC16A14 TRIB3 KLF13AC010170.1 ADRA2C ODAM PDE2A BAMBI C3orf58 HSPA5 IMMP2LTMEM158 HS3ST1 DBI BCHE MGAT1 FTH1P12 RP11-529H2.2 EIF1AYTHBS1 CKS2 AC093162.5 FHOD3 PTGER4 COL17A1 DDIT4 OATCA4 CBLB RETSAT EXOG SREBF1 TMEM116 MPZL2 ANKRD43YPEL2 TLL2 IRF6 TNFRSF21 PRPH ORMDL3 RIT1 PYGBSCGN IDH1 GC TRIB2 DENND5A CRYAB GPRC5B ZBTB16CAMK2N1 LGALS4 SH3BP4 SOCS2 AP3M2 TBX3 TUFT1 TWF2FAM47E HLX MMP15 NFIB CSRP1 RP11-298P3.4 NAP1L3 IFI6STBD1 PODXL CRABP2 SCARB2 RHOB CCNG2 GRPEL2 C1orf21DEPTOR PHLDA1 DUSP10 TMEM2 GPT CMTM8 ELOVL4 ATP1B1PHGR1 PIK3IP1 LRRTM4 PPIC SHROOM1 SHROOM3 DEGS2 AL139819.1SYT17 AMOT CITED1 MUC13 GFOD1 KRT8 ATP7A SCDALDH4A1 SOX9 EDN2 S100A11 CEBPG FADS2 HIST1H2AC SNORD88CASS1 CITED4 DDIT3 LINGO1 PIM1 MAT2A MAP1B PLXDC2AC012621.2 BTG1 LGALS3BP ENPP4 LRRN1 TMEM51 FAM43A TRAK2POLB STX3 CD24P4 LPIN1 LIMCH1 CANX MERTK SERPINI1LCN2 SLCO2A1 TLE1 KLK3 NUP54 IRF1 CAPN2 PCK2TMOD1 MOSC2 PDIA4 GADD45A SCGB2A1 ERO1L HTR3A PIGRC1orf115 CENPN MOCOS ENPP5 FTH1 FAM102A MATN2 IFI44CRIP2 ST8SIA2 PELI2 U6atac.22 JARID2 NEURL3 ITPR1 PDGFCFAM174B RARRES3 CSRNP1 ALCAM DNASE1L3 TEAD2 SCRG1 PRDM8SEMA3F MFSD6 DNAJB9 OSBP HSD11B2 FTH1P11 SDC2

8

4 Expression analysis for GR

Group Definition DescriptionsiCEx median(siCEx 1, siCEx 2) GR controls for the parental cellssiCDx median(siCDx 1, siCDx 2) GR cases (dexamethasone) for the parental cellssiFEx median(siFEx 1, siFEx 2) GR controls for siFOXA1siFDx median(siFDx 1, siFDx 2) GR cases (dexamethasone) for siFOXA1fcsiCx ratio(siCDx/siCEx) GR dexamethasone samples divided by their controlsfcsiFx ratio(siFDx/siFEx) GR dexamethasone siFOXA1 samples divided by their

controls

Table 8: Sample groups

siCEx (median)

fcsiCx (ratio)

siCDx (median)

siFEx (median)

fcsiFx (ratio)

siFDx (median)

siCEx_1

siCEx_2

siCDx_1

siCDx_2

siFEx_1

siFEx_2

siFDx_1

siFDx_2

5 Summary of DEGs in GR

Gene set SizefcsiCx fcOver 471fcsiCx fcUnder 120fcsiFx fcOver 532fcsiFx fcUnder 269

6 List of differentially expressed genes

Overexpressed genes are sorted with the most overexpressed first and underexpressed genes with the most underexpressed

first. Genes go by the column first and then by row.

6.1 Gene set: fcsiCx fcOver


PGC NFKBIA ABCD3 ITGA1 KCNK1 TNKS1BP1 RHBDF1 TMED9TUBA3D RP5-955M13.3 CYP1A2 PYGB KLF6 KIAA0513 CYP11A1 ZCCHC6S100P SLC22A23 LCP1 JAK2 MYL12A STT3A ZBTB25 PHF17TUBA3E CDC42EP4 FAM129B GBE1 ACSL1 PSMD8 GOLGA2 TGFBR3CST1 SLC10A1 DHCR7 PITX1 AC061975.8 TNFRSF12A CD99 KLF9TIPARP KRT72 WIPI1 PHACTR2 AGPAT6 DGCR2 C1orf21 ATOH8TUBA3C ATP1A1 NCRNA00287 FAM65B C6orf81 EMILIN3 MLPH PSME4RASD1 FADS1 TRNP1 HARS OSBPL5 THOC5 ELF1 IQGAP1

9

TMEM56 PPAP2A OFD1 IYD BBS10 TRIM24 SLC33A1 C5orf46ACTA2 ABCC8 SPINK13 MRFAP1 TMED5 EDEM1 TMED10 NEDD4LFKBP5 SPSB1 CTD-2048F20.1 LRRFIP2 SEC23B PDZD2 EFNA1 RP11-802E16.3CEBPD AL358252.1 CAPN13 ATG16L1 F2RL1 HAPLN3 EGFLAM ACTN1PNLIP CLEC16A SPOCK1 PTPLA CKB ZNF189 ENPP1 IL6RLEPREL1 MUM1L1 AC217785.3 PDIA5 C1orf122 DERA GPR89C KLK3SGK1 TUBB2A AL713999.2 LRRC8A C13orf15 GORASP1 SLC29A2 SLC41A2CTGF PEBP4 GBA PLXNB2 CALU MEAF6 SSX2IP ARL8BSLC25A18 PHACTR3 ZDHHC8P1 TTC21A TMEM43 PRKCE ZFAND5 GFPT1DUSP1 SLC4A7 STX12 TSC22D3 CSRNP1 SORT1 WDYHV1 TSC2CRISPLD2 C9orf152 TDRD9 C17orf48 ZBTB24 CNN2 VPS37B JUNFOS AL162497.1 SLC5A6 C1orf172 ENPP3 IP6K3 ZC3H12A AC138649.1ERRFI1 IRS2 BIRC3 AL391319.1 AZGP1 BRP44 GIPC1 SGSM2CHST3 KLF15 FERMT2 SMOC2 B3GAT1 ARSA GPR89A RP11-61N20.3LONRF1 ETNK2 ITGB1 ZBTB16 AZI2 SOD2 DEXI GOLGB1SNAI2 PRKAB2 MAFB KIAA1826 C17orf91 SURF4 ACAT2 RRASOGFRL1 TSKU PPL SQLE STK35 AL593848.10 BIRC2 PTPRGC17orf80 TSPYL2 TPM1 RP11-529H2.2 AC093162.5 GMNN NAT1 TSC22D1ELL2P1 FBXO31 FAM107A FBRSL1 RETSAT SLC2A1 SLC30A7 LZTR1ELL2 KRT8 SLC38A2 CA4 PDE9A RRBP1 KIAA1191 CLIC4PTGER4 PHGR1 DNAJB9 SOCS2 KIAA0232 HSD17B11 ASB13 WDFY2SRD5A1 SC4MOL AC093323.3 AGT EEF2K ZCCHC11 MICAL1 CLINT1CYR61 RP11-397D21.1 RP11-125K10.4 HEXDC LASS6 AP001468.2 SRPRB PER1FOXO1 SLC44A3 RCL1 AC023024.1 KLHL36 CLMN DHX36 GOLGA5FAM105A LRIG1 TEDDM1 MED23 CLPTM1L GLUD1 PEA15 MOCOSPHLDA1 ZFP36 SLC27A3 GSTM3 PPTC7 C8orf84 ACTB RPN1PDLIM1 CAP2 CAPN2 CPEB4 HSD17B4 NANS CAB39 GOT1STK39 RNASE12 PALLD TP53I3 CLGN BTD MAP1LC3B ALDH3A2SLC39A14 NPC1 USP10 JAG1 PDHA1 SRPR BBX PNPLA8KRT73 SLCO4A1 TBC1D8 SEC61A1 SSR3 SUN2 FAM114A1 KIF5CSLC30A1 ARG1 SHROOM3 GATSL3 PACSIN2 INSIG1 C14orf147 MGAT1GNMT DOCK5 SLC31A2 RP1-130H16.18 DNER HOMER2 ZMYND8 ATP11BRGS2 OLAH SERPINA3 SAR1B TRAM1 MYBPC1 CEBPB CRY1ST3GAL4 PHLDA2 STRBP OSBPL11 SYBU SPRY2 TMEM39A MOGSCITED1 PAK1IP1 PROS1 TOR1AIP2 HMGCS1 TACC2 AC004893.11 TXNDC11SLC39A11 GADD45B NUDT16 ODC1 SSR1 CTD-2653M23.1 TRRAP PELOAPOD TPD52L1 STAT3 SNX33 FADS2 HYOU1 PPA1 MBNL1CDKN1C ATAD2 ZFHX3 TMEM61 RNASE11 GPR89B CD9 WI2-3658N16.1MBOAT2 PQLC1 SLC16A3 SEC24D CCDC6 SOCS1 LSS MAN2B2GBP2 KCNMA1 PLEKHF1 IDI1 OLFML2B SAT1 TNFAIP3 BCAP31SCNN1G CREB3L2 AASS CALD1 TMEM91 ABHD3 DOLK C15orf23MFSD6 ELOVL5 RNASE4 GLRX NFIL3 CCBL1 ACSL3 ANKRA2NSDHL CTDSPL SCAP CR759786.11 RNF115 FAM190B PPP2CB XPR1ANO6 MSX1 AP001468.1 AL844527.3 TACSTD2 ELOVL1 RP1-96H9.6 F5RHOB CH17-12M21.1 ANG CR759817.7 STEAP4 PHLPP2 TNFRSF1A TP53INP2COL6A2 CST3 NET1 AL662827.4 ANXA5 MCEE MAP3K6 NKTRCES4A SLPI LRRC16A B3GALT4 RP11-458D21.5 ZDHHC9 HIPK2 AMOTGHR ZNF185 DBI TGM1 AP3S1 DDX19A C1orf198 AC063976.6LIFR DHCR24 MERTK TMEM49 RBM24 FXYD3 AL118511.2 P4HA2COL6A1 CA12 ASIP ACAA1 KIAA1324L TWF2 WDR60 USP38VCL GBAP1 DLG5 TNFRSF10A FIG4 C3orf70 GOLPH3

6.2 Gene set: fcsiCx fcUnder


TGM3 AL589734.1 SLITRK3 HOXC9 NUP93 MT1A LRRC26 AC008738.1RASL11B SEPT3 COL16A1 C12orf48 RP11-611D20.2 NIPSNAP3A C20orf27 SPTBN5ACPP CCDC59 DCTPP1 PRR7 MCM6 CFD C5orf30 RAI14BAMBI TRIB1 RP11-118B22.3 SLC25A19 HJURP CKAP2L ID2 RP3-470B24.5CARM1 TUBB4 RP11-267J23.4 C9orf140 DHRS13 RP11-1198D22.1 Z83851.1 FIGNL1DDC F12 ZIC2 CCDC85B AIF1L FKBP1C TOX3 WDR54AC100826.1 GATA2 NFIX HOXB13 CTB-161M19.3 HIST3H2A IRF2BPL GUSBP3CAMK2N1 GINS2 CBLN2 CDCA5 PTMA CXCL16 DBP EFHC2PAQR4 BCHE LMO4 CPNE4 FOLH1 CXXC5 FZD2 LMNB1FAM198B MAST4 C13orf38-SOHLH2 MAPKAPK3 LYSMD2 ANKRD16 ZMYND15 RP11-543B16.1MESP1 CXCR7 CACNB3 NKD2 KBTBD11 LRRN1 CMBL ELL3HOXC13 AMACR HES6 COLEC12 ISG15 GUSBL1 FKBP1A C12orf24HBQ1 TUBA4A AC010170.1 TRIM68 PSMB10 CLDN3 TYMS SIGIRRRP11-181C21.4 AC005017.2 TMEM158 DEGS2 MT1F AC073465.3 MCM2 PRKD1HMGCS2 GLDC TERC UGT2B17 MYC SLC7A5 TRAP1 PPP1R14B

6.3 Gene set: fcsiFx fcOver


10

TUBA3D MBOAT2 DHCR7 PRDX6 AZI2 B3GAT1 LAMB1 COPS8TUBA3E AC217785.3 MERTK UGP2 MICAL1 AC135995.3 KRT16 GEMIN8RASD1 AL713999.2 PRKAB2 DLX1 SAA2 AC126339.2 PEA15 OSBPL10TIPARP GBA CTDSPL AC010296.1 C15orf23 AC010724.5 TTC39B WTAPTUBA3C AL391319.1 PEBP4 SEMA6A AUTS2 AC136698.2 CLDN12 PDZD8TMEM56 SMOC2 PTPRG MUM1L1 AC073873.1 AC044860.4 HSD17B11 MORF4L2S100P OLFML2B ZBTB24 RBM24 C6orf52 AC004383.4 TXN KIAA0232PGC HEXDC SYBU C6orf81 NFIL3 ARSA RP11-802E16.3 AC063943.1FKBP5 TSPYL2 ODC1 GIPC1 TNFAIP3 DOCK5 C16orf93 NFE2L2CEBPD KLF15 OFD1 TRIM24 EGFLAM C12orf44 FDFT1 CCDC84C17orf80 DERA SOCS2 AL590369.1 THOC5 MEAF6 TFAP2C IRAK1CITED1 DHCR24 SF3B5 PTGES PLXNB1 C14orf147 CCNF EFNA1CRISPLD2 SLCO4A1 PDHA1 MAPRE3 MYBPC1 GOLPH3 ITPK1 SAMD8FOS HBB KRT8 AGPAT6 PDE9A MAP7D1 SAP30 AC135995.4CTGF ATAD2 LCP1 AASS TP53INP2 NAT2 PELO AC010724.6PDLIM1 STK39 GADD45B SLC29A2 IQGAP1 TWF2 RGS19 RNFT1DUSP1 HOMER2 SQLE RNF115 TOR1AIP2 HSD17B4 RAB32 TSKUCES4A SOCS1 HSPB8 FADS2 PRKCE CCDC107 PHKA1 C5OGFRL1 SLC39A11 JUN PARP12 SLC9A2 FERMT2 PIAS1 MFSD6TUBB2A ETNK2 KCNMA1 DLL1 CAPN2 ELF1 ZFYVE20 C5orf51CYR61 CALD1 PIR PANX1 DPP4 KIAA0040 AC023024.1 UBQLN1RP5-955M13.3 GPD1L OLAH ZNF185 TNKS1BP1 FGFRL1 FAS TAF1BCHST3 VCL GHR ZNF189 CST1 NCKIPSD FAM189B ENPP3SGK1 CLPTM1L RP1L1 SNX33 GSTM3 TMEM63C EBP SUN2SPOCK1 AC093323.3 AP3S1 TMEM61 PLXNA2 DNAJC3 COBLL1 FAM199XPITX1 PQLC1 TNFRSF12A SH3PXD2B SOX8 PHF17 AC126339.3 AKR1C3ERRFI1 PALLD USP10 MRFAP1 KIAA1191 ASIP KIAA0913 LGMNCOL6A2 FBXO31 PPL AP001468.1 DHX36 KLHL36 C7orf53 TLN2TRNP1 ELOVL5 C17orf91 NUDT16 C17orf48 MRPL11 PLCXD1 DBIC8orf84 NFKBIA SCAP PHLDA2 ZFHX3 TGM1 OSBPL5 CYP51A1ELL2P1 FRMPD3 EPAS1 SHC1 FAM107A DNAJB9 HMGCS1 ALDH3A2ELL2 STX12 NAT1 CH17-12M21.1 EVL FDPS PPA1 HAPLN3SERPINA3 ABCC8 CTD-2048F20.1 HPCAL4 GLRX KCNG1 C5orf32 DYNLL1ACTA2 SLC30A1 LRRC16A ELOVL1 RP11-61N20.3 ABHD2 GNRH2 CCBL1PGF TSPAN3 NCRNA00287 CPEB4 PDZD2 NAV2 DNER MAPK6COL6A1 GBP2 NUDT11 GNMT XPR1 BBS12 WDR55 DAPK3SNAI2 KLF6 PTPLA ERICH1 LSS EIF2AK3 STK17B BTBD10SOD2 NET1 CNKSR3 SAA1 TMEM120A MYL12A UAP1 DVL2SRD5A1 CST3 GBE1 TTC21A P4HA2 ATG16L1 RP1-96H9.6 ABCF3SLC39A14 EMILIN3 RP3-437C15.1 SWT1 RP11-458D21.5 SEC14L1 TNFRSF1A AC061975.8SLC4A7 ITGB1 CLEC16A GMNN FTH1P3 CKB IP6K3 PNMA1TPD52L1 C1orf172 SLC22A23 WIPI1 CR759786.11 CIDEC TCEAL4 FTH1P12SLC44A3 ITPKA C1orf198 ATF6 AL844527.3 AP001468.2 RBMS3 PCYT2FADS1 SLC5A6 AL118511.2 MAP1LC3B CR759817.7 EIF2B2 CYorf15A HBP1PNLIP SLCO2A1 SC4MOL ACAT2 AL662827.4 RHBDF1 HYOU1 PPP3CCLONRF1 S100A10 RP11-397D21.1 MRPS23 B3GALT4 AC010335.1 WWC3 PLCG1ATP1A1 SLC25A18 CDKN1C SLC6A6 MGST1 ELL TAX1BP3 CTDP1PAK1IP1 RHOB HARS C5orf46 NRCAM MAP3K6 AC110814.1 PHKG2C9orf152 ABCD3 PHLDA1 FBRSL1 LRRC8A STAT3 SCAMP3 C1orf122SPINK13 PHACTR2 FIG4 SLC27A3 FLNA DOLK WI2-3658N16.1 PTPRN2PLEKHF1 AL162497.1 KIAA1826 DLG5 CLGN PPP2CB DUSP23 TACSTD2FOXO1 IRS2 CCDC6 RAD51C C8orf42 MED23 KRT16P3 AC092037.3ACPL2 JAK2 IDI1 RBBP7 RP11-529H2.2 AC010889.1 HS1BP3 MANFLIFR PROS1 BBX BBS10 ASCC1 CYorf15B ACSL3 RRASNSDHL RP11-125K10.4 DGCR2 DDIT4 COPS3 VEZF1 SHISA2 C6orf62TEDDM1 RCL1 STRBP HSD17B2 JAG1 EZR ELMOD2 IFRD1PHACTR3 FAM105A ZFP36 RNASE11 PSMD8 LIN7B AC044860.3 SLC22A5CAP2 PPAP2A PLXNB2 FAM65B YWHAQ TP53BP2 ELK1 UBE2Q2P2ST3GAL4 SLC31A2 CA12 C3orf70 TRAPPC2P1 APEX2 AMDHD2 RAB40AQSOX1 TSC22D3 ACSL1 TPM1 OSBPL11 CAB39 PCYOX1L CAP1LEPREL1 CRYAB TBC1D8 MIPEP CNN2 SORT1 C1orf85 BRP44CDC42EP4 SCNN1G LASS6 EPHB6 GOT1 BZW1P2 USP3 AACSGBAP1 FAM129B NPC1 TMEM43 PYGB STEAP4 GBP1 ZDHHC9SPSB1 OVGP1 GOLGA5 PTGER4 SPON2 ENPP1 LTV1AL358252.1 STK35 SSR3 SEC23B AC063976.6 IGF2R VILLRNASE12 ZDHHC8P1 AP1S2 TTLL12 PPP1R14C FTH1P11 CLMNANO6 TDRD9 ACAA1 Z82214.1 MYH10 ANXA5 GPSM2

6.4 Gene set: fcsiFx fcUnder


POLB RP11-1280N14.4 MT1F RP11-611D20.2 GFOD1 EFNB3 IMMP2L GPT2LRRTM4 RP11-98J23.2 CXCR7 PIM1 CGNL1 INSL5 CRABP2 CCDC28BCOLEC12 RP11-497H16.5 C4orf11 TSPAN9 RPSA RP3-470B24.5 ELL3 SIPA1L2DEPTOR GUSBP1 LYSMD2 GOLIM4 PLAT CCDC85A SCNN1D NLGN1RP11-181C21.4 RP11-1415C14.3 NAP1L3 DHRS13 SELENBP1 CDK1 SLC39A8 MBLAC2

11

HOXC13 AC108108.1 FAM174B TYMS RXRA LUZP2 FLOT2 AC093510.1BAMBI RP11-823P9.1 SH3RF1 NOTCH1 KLHDC5 NCRNA00219 DHRS4L2 CPNE3RP11-543B16.1 SEMA3F SLPI PRMT3 RP11-31K13.1 NUPR1 DKC1 MEF2CAP3M2 PRPH PPP1R14B VDAC3 ADA CMBL HCP5 ZMYND15ASS1 CLDN3 PSMB10 WDR54 AMACR SLC7A5 HCP5 GINS2AC010170.1 CBLN2 HTR3A HIST3H2A ZBTB43 LMO4 HCP5 SNORD14DTMEM158 FAM47E FOLH1 PIK3IP1 HOXA5 SLC16A14 HCP5 SLC25A19MYC STBD1 ABCC4 TBL1XR1 AIDA TARS RP11-781P14.3 ANKRD46LRRC26 CAMK2N1 GLDC ACOX2 ELF3 TOP2A FAM102A TMEM123MESP1 NETO2 PAQR4 MYO6 C1orf115 CSPG5 C5orf30 SLC2A4RGZG16B GUSBL1 FKBP1A EFCAB4A C1orf116 PRR7 SPTBN5 SOX9VASN TLL2 LINGO1 PIK3AP1 KBTBD11 SDC4 RP11-497H16.8 ADORA2BZ83851.1 SYT17 IRF2BPL DEGS2 PPP2R2A NDUFAF4 XXbac-BPG55C20.1 SERPINI1PRKD1 COL16A1 AC008738.2 TUBA4A AC012621.2 CACNB3 MSRB2 ANKRD43ACPP RP11-510N19.5 CEBPA LGALS4 PARD6A GDF15 ZNF467 NFKBIZGATA2 ADRA2C CFD CXCL16 NEFH HIBADH RAI14 TMEM117SLITRK3 TRIB1 HBQ1 AIF1L CITED2 BRIX1 MCM6 ADAP2RP11-1198D22.1 C12orf48 RP11-589F5.4 CGN MANEA GPT ABHD11 CDCA5FOXA1 GUSBP3 RP11-1415C14.4 CHTF18 IL1RAPL1 PRAC PROM2 AQP11LRRN1 CBLB FKBP1C TGIF2 CDK5R2 TP53INP1 AC016712.2 TCEA2F12 TSPAN15 HOXC9 PODXL YPEL2 ATP12A CCDC14 HNRNPA1P10ZNF503 C9orf140 CCDC59 GDE1 H2AFY2 FERMT1 PCBD1 MUC13MT1A ENPP4 MOSC2 SDSL KLHL35 GFOD2 GULP1 NKD2HLX DDC ILDR1 C19orf48 EFR3B RAP1GAP SHROOM1 HJURPNUP54 TOB1 RSL24D1 SNORD88B MAPKAPK3 RIT2 TLCD1 BARD1SEPT3 MAL2 FAM65A PRR15L MOSC1 ISG15 THNSL1 GRAMD1CODAM HIST1H4C TSPAN8 TRIB2 ADAMTS1 RALYL PPP1R16ACCNG2 TOX3 HSD3B7 PPFIA2 YEATS4 RNF144A LIN7ABCHE PELI2 CYFIP2 SERHL2 RHPN2 HS3ST1 MYLK

Table 13: Pathway effects of AR DTH (S1) and siFOXA1 DHT (S2) as predicted by SPIA.

ID Name S1 p S1 status S2 p S2 status

hsa05221 Acute myeloid leukemia 0.7815 Activated 0.9992 Inhibitedhsa04920 Adipocytokine signaling pathway 0.3595 Inhibited 0.9992 Inhibitedhsa05143 African trypanosomiasis 0.7537 Activatedhsa04960 Aldosterone-regulated sodium reabsorption 0.3595 Activated 0.2230 Activatedhsa05010 Alzheimer’s disease 0.8946 Inhibited 0.9992 Activatedhsa05146 Amoebiasis 0.9992 Inhibitedhsa04612 Antigen processing and presentation 0.6735 Inhibitedhsa04210 Apoptosis 0.9998 Inhibited 0.9992 Inhibitedhsa04360 Axon guidance 0.9998 Activated 0.9992 Inhibitedhsa04662 B cell receptor signaling pathway 0.9998 Inhibited 0.9992 Inhibitedhsa05100 Bacterial invasion of epithelial cells 0.9998 Inhibited 0.4870 Activatedhsa05217 Basal cell carcinoma 0.5737 Inhibited 0.9992 Activatedhsa04976 Bile secretion 0.5803 Inhibited 0.9992 Inhibitedhsa05219 Bladder cancer 0.9992 Inhibitedhsa04020 Calcium signaling pathway 0.9998 Inhibited 0.9992 Inhibitedhsa04973 Carbohydrate digestion and absorption 0.9998 Inhibited 0.9992 Inhibitedhsa04110 Cell cycle 0.9992 Inhibitedhsa05142 Chagas disease (American trypanosomiasis) 0.9998 Inhibited 0.5575 Activatedhsa04062 Chemokine signaling pathway 0.9998 Inhibited 0.9992 Activatedhsa05220 Chronic myeloid leukemia 0.9998 Inhibited 0.4870 Inhibitedhsa05210 Colorectal cancer 0.7537 Activatedhsa04610 Complement and coagulation cascades 0.9998 Inhibited 0.9992 Inhibitedhsa04060 Cytokine-cytokine receptor interaction 0.9998 Inhibited 0.9992 Inhibitedhsa04623 Cytosolic DNA-sensing pathway 0.9998 Inhibited 0.9992 Inhibitedhsa05414 Dilated cardiomyopathy 0.9992 Inhibitedhsa04320 Dorso-ventral axis formation 0.9992 Inhibitedhsa04512 ECM-receptor interaction 0.9998 Activatedhsa05213 Endometrial cancer 0.9992 Inhibitedhsa05120 Epithelial cell signaling in Helicobacter pylori infection 0.9998 Inhibited 0.9992 Activatedhsa04012 ErbB signaling pathway 0.9998 Activated 0.7525 Activatedhsa04664 Fc epsilon RI signaling pathway 0.9992 Activatedhsa04666 Fc gamma R-mediated phagocytosis 0.9998 Inhibited 0.9216 Activatedhsa04510 Focal adhesion 0.9998 Activated 0.6440 Activatedhsa04540 Gap junction 0.9998 Inhibited 0.9992 Inhibitedhsa04971 Gastric acid secretion 0.9998 Inhibited 0.9992 Inhibitedhsa05214 Glioma 0.9998 Inhibited 0.9992 Activatedhsa04912 GnRH signaling pathway 0.9992 Inhibitedhsa04340 Hedgehog signaling pathway 0.9998 Inhibitedhsa05160 Hepatitis C 0.9998 Inhibited 0.8857 Activatedhsa05016 Huntington’s disease 0.9998 Inhibited 0.9992 Inhibitedhsa04910 Insulin signaling pathway 0.5737 Inhibited 0.0803 Inhibitedhsa04630 Jak-STAT signaling pathway 0.6000 Inhibited 0.4870 Inhibitedhsa05140 Leishmaniasis 0.9998 Inhibited 0.9992 Inhibitedhsa04670 Leukocyte transendothelial migration 0.9998 Inhibited 0.9992 Activatedhsa04730 Long-term depression 0.9998 Inhibited 0.9992 Inhibitedhsa04720 Long-term potentiation 0.9992 Inhibitedhsa04142 Lysosome 0.9998 Inhibited 0.9992 Inhibitedhsa04010 MAPK signaling pathway 0.9998 Inhibited 0.9992 Activatedhsa05144 Malaria 0.9998 Inhibitedhsa04950 Maturity onset diabetes of the young 0.3595 Inhibited 0.7537 Inhibitedhsa04916 Melanogenesis 0.6735 Inhibited 0.9992 Activatedhsa05218 Melanoma 0.9992 Inhibitedhsa04621 NOD-like receptor signaling pathway 0.9998 Inhibited 0.9992 Inhibitedhsa04650 Natural killer cell mediated cytotoxicity 0.9992 Activatedhsa04080 Neuroactive ligand-receptor interaction 0.5737 Inhibited 0.9992 Inhibitedhsa04722 Neurotrophin signaling pathway 0.9998 Activated 0.7525 Activatedhsa05223 Non-small cell lung cancer 0.9992 Inhibitedhsa04330 Notch signaling pathway 0.8036 Inhibited 0.8561 Inhibitedhsa04114 Oocyte meiosis 0.9992 Inhibitedhsa04380 Osteoclast differentiation 0.9998 Inhibited 0.9992 Activatedhsa03320 PPAR signaling pathway 0.9133 Inhibited 0.9992 Inhibitedhsa05212 Pancreatic cancer 0.9992 Activatedhsa04972 Pancreatic secretion 0.8036 Inhibited 0.9992 Inhibitedhsa05012 Parkinson’s disease 0.9998 Inhibited 0.9992 Inhibitedhsa05130 Pathogenic Escherichia coli infection 0.3595 Activated 0.4870 Activatedhsa05200 Pathways in cancer 0.9998 Inhibited 0.8857 Inhibitedhsa05020 Prion diseases 0.9992 Inhibitedhsa04914 Progesterone-mediated oocyte maturation 0.9992 Activatedhsa05215 Prostate cancer 0.5737 Inhibited 0.7537 Inhibitedhsa04141 Protein processing in endoplasmic reticulum 0.9998 Inhibited 0.9992 Activatedhsa04622 RIG-I-like receptor signaling pathway 0.9998 Inhibited 0.9992 Inhibitedhsa03018 RNA degradation 0.9998 Inhibited 0.9992 Inhibited

Continued on next page. . .

12

ID Name S1 p S1 status S2 p S2 status

hsa03013 RNA transport 0.9992 Inhibitedhsa04810 Regulation of actin cytoskeleton 0.9992 Activatedhsa05211 Renal cell carcinoma 0.7537 Activatedhsa05323 Rheumatoid arthritis 0.7525 Activatedhsa04970 Salivary secretion 0.3595 Activated 0.7903 Inhibitedhsa05131 Shigellosis 0.9998 Inhibited 0.9992 Inhibitedhsa05222 Small cell lung cancer 0.9998 Inhibited 0.9992 Inhibitedhsa05150 Staphylococcus aureus infection 0.9992 Inhibitedhsa05322 Systemic lupus erythematosus 0.0003 Inhibitedhsa04660 T cell receptor signaling pathway 0.9998 Inhibited 0.9992 Activatedhsa04350 TGF-beta signaling pathway 0.9998 Inhibited 0.9992 Activatedhsa04742 Taste transduction 0.9992 Inhibitedhsa04530 Tight junction 0.9310 Activated 0.4870 Activatedhsa04620 Toll-like receptor signaling pathway 0.8210 Inhibited 0.9992 Inhibitedhsa05145 Toxoplasmosis 0.9998 Inhibited 0.9992 Activatedhsa04930 Type II diabetes mellitus 0.3595 Inhibited 0.5575 Inhibitedhsa04370 VEGF signaling pathway 0.9998 Inhibited 0.9992 Inhibitedhsa04270 Vascular smooth muscle contraction 0.5761 Activated 0.8406 Inhibitedhsa04962 Vasopressin-regulated water reabsorption 0.9799 Activated 0.9992 Activatedhsa04310 Wnt signaling pathway 0.9998 Inhibited 0.9992 Inhibitedhsa04150 mTOR signaling pathway 0.7815 Inhibited 0.9992 Inhibitedhsa04115 p53 signaling pathway 0.9992 Inhibited

13

7 Gene set overlaps

AR

upAR siFOXA1

10029 1329

1601

10766 4

149

(a)

FOXA1

upAR siFOXA1

4043 2124

5830

16719 10

187

(b)

AR

downAR siFOXA1

10025 1833

1599

10866 6

49

(c)

FOXA1

downAR siFOXA1

4053 1214

5818

16779 22

127

(d)

Figure 1: Intersections of sets: (a) AR, up and AR siFOXA1 (b) FOXA1, up and AR siFOXA1 (c) AR, down and ARsiFOXA1 (d) FOXA1, down and AR siFOXA1.

14

DHT upDHT up (siFOXA1)

154107 88

(a)

DHT down

DHT down (siFOXA1)

13162 44

(b)

DEX upDEX up (siFOXA1)

207146 325

(c)

DEX down

DEX up (siFOXA1)

19243 77

(d)

Figure 2: Intersections of sets: (a) DHT up and DHT up (siFOXA1) (b) DHT down and DHT down (siFOXA1) (c) DEX upand DEX up (siFOXA1) (d) DEX down and DEX up (siFOXA1).

15

GRGR siFOXA1

67042385 8675

(a)

GR AR

49823522 7538

(b)

GR siFOXA1 uniqueAR siFOXA1 unique

42042691 2005

(c)

Figure 3: Intersections of sets: (a) GR and GR siFOXA1 (b) GR and AR (c) GR siFOXA1 unique and AR siFOXA1 unique.

16

8 Gene set comparison

Unique DEGs for AR

Common DEGs for AR and siFOXA1Unique DEGs for AR with siFOXA1

283 1320

167

2 0

0

(a)

red

bluegreen

56 260

29

1 0

0

(b)

Figure 4: Intersections of sets: (a) Unique DEGs for AR, Common DEGs for AR and siFOXA1 and Unique DEGs for ARwith siFOXA1 (b) red, blue and green.

Vertex fill colors:

no matching annotations

Unique DEGs for AR

Unique DEGs for AR and Unique DEGs for AR with siFOXA1

Unique DEGs for AR with siFOXA1

Unique DEGs for AR with siFOXA1 and Common DEGs for AR and siFOXA1

Common DEGs for AR and siFOXA1

Unique DEGs for AR and Common DEGs for AR and siFOXA1

Unique DEGs for AR and Unique DEGs for AR with siFOXA1 and Common DEGs for AR and siFOXA1

dephosphorylat iong e n e

expressiong e n e

repressionp a t h w a y

precedencephosphorylat ion

prote inactivation

prote inbinding

prote indissociation

prote ininhibition

Figure 5: Descriptions of the edge types and the gene colors used in the candidate pathway shown in Figure 6. Green andblue borders are referring to up and down regulated genes, respectively. Light grey is used to emphasize stably expressedgenes. Known regulations are shown with bold borders whereas the predictions are kept thin.

17

ABAT

ALDH3A2

CARNS1

GAD1

GAD2

HIBADH

ABL1

GRB2

RAC1

SHC1

STAT5A

STAT5B

ABP1

AGMAT

ODC1

SAT1

SRM

AC008810 .1

ACACA

ACACB

MTOR

AC023024 .1 ,MARCH6

UBE2G1

ACAA1

ALDH6A1

EHHADH

HADH

ACAD8

ACADL

ACSL3

ACTB

ACTN1,ACTN2,ACTN3,ACTN4

CTNNA1,CTNNA2,CTNNA3

EZR

MYH1,MYH11,MYH13,MYH15,MYH2,MYH3,MYH4,

MYH7B,MYH8

MYH10,MYH14

MYH6

MYH7

MYH9

MYL10,MYL12A,MYL12B,

MYL5,MYL7,MYL9,MYLPF

MYL2

PFN1,PFN2,PFN3,PFN4

TJP1

TJP2

TJP3

VCL

ACTC1

TPM1

ACTG1

AD000685 .1 ,CYP4F11,

CYP4F2

ALOX12

ALOX15ALOX15B

ALOX5

CYP2E1

CYP2J2

JMJD7-PLA2G4B,PLA2G10,

PLA2G12A,PLA2G1B,PLA2G2A,PLA2G2F,PLA2G3,

PLA2G4A,PLA2G4B,PLA2G4E,PLA2G5,PLA2G6

PLA2G12B,PLA2G2C,PLA2G2D,PLA2G2E

PLB1

P T G S 1

P T G S 2

ADCY1,ADCY3,ADCY8

ENTPD1

ENTPD3

ENTPD8NME1,

NME1-NME2,NME2,NME3,NME4,NME5,NME6,NME7

PDE2A

PKLR,PKM2

POLR3GL

ADCY10

ADCY2,ADCY5,ADCY6,ADCY7,ADCY9

ADCY4

ADH1A,ADH1C,ADH4,ADH5,ADH6,ADH7

ALDH1A3

ALDH3B2

COMT

DGAT1

MAOA

MAOB

ADH1B

ADRB2

ARRB1,ARRB2

AGPAT1,AGPAT2

AGPAT6,AGPAT9,

GPAM

DGKA,DGKH,DGKZ

DGKB,DGKD,DGKE,DGKG,DGKI,DGKQ

PPAP2A

PPAP2B

PPAP2C

C17orf48

AKR1B1

SORD

AKR1C4

HSD11B2

UGT1A1,UGT1A10,UGT1A3,UGT1A4,UGT1A7,UGT1A8,UGT1A9,UGT2A1,

UGT2B10,UGT2B11,UGT2B15,UGT2B4,UGT2B7

UGT1A5,UGT1A6,UGT2A3

UGT2B17,UGT2B28

AKR1D1

HSD17B2,HSD17B6,HSD17B8

HSD3B1,HSD3B2

AKT1,AKT2

FOXO1

GSK3B

MAP2K4

NFKBIA

AKT3

ALAS1

GLDC

ALAS2

ALCAMCD6

ALDH18A1

ALDH4A1

GLUD1

NAGS

AOC2,AOC3

CYP4A11

CYP4A22

GATM

GLS,GLS2

GLUL

PRODH

ALOX12B

CYP2U1

AMD1

SMS

AMT

DLD

AMY1A,AMY1B,AMY1C

PYGB

PYGL

AMY2A,AMY2B

APBB1,NAE1

APP

ASAH1,ASAH2

DEGS2

ASS1

GOT1,GOT2

IL4I1

OTC

ATP1A1

ATP1B1

B3GALT4

B4GALNT1

ST3GAL1,ST3GAL2

B3GNT6

GALNTL4

BCAP31

SSR3

BCAR1

CRK

PTK2

BTG1

CNOT7,CNOT8

PABPC1,PABPC1L,

PABPC1L2B,PABPC4,

PABPC4L,PABPC5

PABPC1L2A,PABPC3

BTG2

CALD1

CALM1,CALM2,CALM3,CALML3,CALML5,CALML6

HRAS,NRAS

KRAS

PHKA1

CAMKK2

PRKAA2

PRKAB1,PRKAB2,PRKAG1,PRKAG3

PRKAG2

DDC

CBLB

FYN

IL2RA,IL2RG

IL2RB

IL6R

JAK1

JAK2

JAK3

LCK

LEPR

PIK3CA,PIK3CB,PIK3CG

PIK3CD

PIK3R1

PIK3R2,PIK3R3,PIK3R5

RAPGEF1

TYK2

ZAP70

CCND3

CEBPG

CEL

DHCR24

LIPC

LIPFLIPG

PNLIPPNLIPRP1

PNLIPRP2

PNLIPRP3

PNPLA3

SOAT1,SOAT2

CEPT1

CHPT1

EPT1

MBOAT2

PLD1

PLD2

CGN

CLDN1

CLDN10

CLDN11

CLDN14

CLDN15

CLDN16

CLDN17

CLDN18

CLDN19

CLDN2

CLDN20

CLDN22

CLDN23

CLDN3

CLDN4

CLDN5

CLDN6

CLDN7 CLDN8

CLDN9 ESAM

INADL

MPDZ

OCLN

CREB3L4DOCK2

FCGR1A,FCGR2A,FCGR2C

FCGR3A

FRS2,KIDINS220

MAPK10,MAPK8,MAPK9

PTK2B

CTNNB1

CTPS,CTPS2

ITPA

CYP11A1

CYP17A1

CYP21A2

CYP1A1

CYP2B6

CYP3A4,CYP3A5,CYP3A7

CYP3A43

EPHX1

GSTA1

GSTA2

GSTA3

GSTA4

GSTK1

GSTM1

GSTM2

GSTM3

GSTM4

GSTM5

G S T O 1

G S T O 2

G S T P 1

G S T T 1

G S T T 2

G S T Z 1

MGST1

MGST2

MGST3

CYP1A2

CYP2D6

CYP2F1

DCXR

IDO1

IDO2

TAT

TH

TPH1,TPH2

TYR

ENPP7,SMPD1,SMPD3

SMPD2

SMPD4

DGAT2

PLCB1

PLCB2

PLCB3PLCB4

PLCD1 PLCD3

PLCD4

PLCE1

PLCG1

PLCG2

PLCZ1

DHCR7

LIPA

SC5DL

OGDHL

DLST

DPYSL2

DUSP1

MAPK1,MAPK3

MAPK11,MAPK12,MAPK13,MAPK14

DYNC1H1,DYNC1I1,DYNC1I2,

DYNC1LI1,DYNC1LI2,DYNC2H1

TUBA3D

EGFR

ERBB2

NTPCRPNPT1

ETS2

ICAM1

VCAM1

F12

PLG

F2RL1

FADS2

FASN

OLAH

OXSM

FLT1

FLT4

PPARGC1A

GAB2

FZD2

GNAO1

LRP5,LRP6

FZD8

GAB1

PTPN11

GGT1,GGT5,GGT6,GGT7

GCAT

GNMT

GBE1

GJA1

RP11-631M21.2

TUBB,TUBB1,

TUBB2B,TUBB2C,TUBB3,TUBB4,

TUBB4Q,TUBB6

GLI1

GLI2

GLI3

WNT5A

ZIC2

HAL

LAT

PDGFRA,PDGFRB

GRM1

HOMER1

HOMER2

HOMER3

GRM5

GYS1,GYS2

GUCY1A3

GUSB

HIF1A

PGF

HK1,HK2,HK3,

HKDC1

PFKFB2

PGM1,PGM2

ITPR1,ITPR2

ITPR3

SHANK1,SHANK3

SHANK2

HSD3B7

IDH1

IDH3A,IDH3B,IDH3G

IGF1R

INPP4A

PIK3C2A

PIK3C2B

PIK3C2G

PIK3C3

PIKFYVE

INPP4B

INSR

IRS1,IRS4

IRS2

STAT1STAT2

STAT3

STAT4,STAT6

JUN

KDR

KL

L1CAM

NCAM1

NCAM2

MAPKAPK3

PPP2R2A

MET

MPZ

MPZL1

PRNP

NFKB1,RELA

NFKB2

NUDT5

PRPS2

NUP54NUP62

PDPK1

PRKCZ

SGK1

UGP2

PIAS1

PIK3AP1

PIP4K2A,PIP4K2B,PIP4K2C

PIP5K1A,PIP5K1B

PIP5K1CPTEN

PIM1

WAS,WASL

PLXNB1

SMG1,SMG5

SMG6

PRKCH

PRSS1

PTGES

PTPN1

SEC61A1,SEC61A2,S E C 6 1 B ,S E C 6 1 G

SEMA4A

SOCS2

SORBS1,TLN1,TLN2

ST3GAL5

ST6GALNAC1

TGFBR1

TGFBR2

TNNT2

UGDH

Figure 6: Candidate pathway for Gene set comparison. Graph notations are described in Figure 5.

18

9 Candidate report for Unique DEGs for AR

9.1 Moksiskaan candidate pathway

AC008810 .1 ,PRKAA2

ACACA

ACACBMTOR

AC023024 .1 ,MARCH6

UBE2G1

CPT1A,CPT1B,CPT1C

ACSL3

ADRB2ARRB1,ARRB2

AKT1,AKT2,AKT3

PIK3CA,PIK3CB,PIK3CD,PIK3CG

PIK3R1,PIK3R2,PIK3R3,PIK3R5

AMD1 SMS

SRM

APBB1,NAE1

APP

ASAH1,ASAH2 DEGS2

ATP1B1

B3GNT6 GALNTL4BTG1 CNOT7,CNOT8

PABPC1,PABPC1L,

PABPC1L2A,PABPC1L2B,

PABPC3,PABPC4,

PABPC4L,PABPC5

CAMKK2

PRKAB1,PRKAB2,PRKAG1,PRKAG2,PRKAG3

CYP11A1

CYP17A1

CYP21A2HSD3B1,HSD3B2

CYP1A1

CYP3A4,CYP3A43,CYP3A5,CYP3A7

HSD17B2,HSD17B6,HSD17B8

UGT2B17

UGT2B28

CYP2D6SMPD2

FZD2

LRP5,LRP6

GLI1

GLI2

GLI3

WNT5A

ZIC2

GUSB,UGDH

IDH1 IDH3A,IDH3B,IDH3G

INPP4B

PIK3C2A,PIK3C2B,PIK3C2G

PIK3C3

PIKFYVE

KL

ST6GALNAC1

g e n eexpression

g e n erepression

p a t h w a yprecedence

phosphorylat ionprote in

activationprote inbinding

prote indissociation

protein-proteininteract ion

Figure 7: Known relationships between the candidate genes. Candidate genes are shown in red if they have only outputconnections. The ratio of input and output connections determines how light they are. Completely white genes have onlyinput connections. The maximum of 1 other gene step(s) are allowed between the candidate genes and these intermediategenes are shown on gray. Green and blue borders are referring to up and down regulated genes, respectively. Light grey isused to emphasize stably expressed genes. Known regulations are shown with bold borders whereas the predictions are keptthin.

Table 14: Descriptions of the intermediated genes between the candidate genes. Studies that have reported results about thecandidate genes are listed so that those with negative evidence have been prefixed with a hyphen. This table has 72 rows.

name description studies

AC008810.1 5’-AMP-activated protein kinase catalytic subunit alpha-1 [Source:UniProtKB/Swiss-Prot;Acc:Q13131]locus=5:40759481-40798476

AC023024.1 Selenoprotein S [Source:UniProtKB/Swiss-Prot;Acc:Q9BQE4] locus=15:101811022-101817705 tcgaGliomaGEACACB acetyl-CoA carboxylase beta [Source:HGNC Symbol;Acc:85] locus=12:109554400-109706031AKT1 v-akt murine thymoma viral oncogene homolog 1 [Source:HGNC Symbol;Acc:391] locus=14:105235689-105262080 cosmicRecurrent, tcgaGliomaGE,

tscapeMelanomadAKT2 v-akt murine thymoma viral oncogene homolog 2 [Source:HGNC Symbol;Acc:392] locus=19:40736224-40791302 tcgaGliomaGEAKT3 v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [Source:HGNC Symbol;Acc:393]

locus=1:243651535-244013430tcgaGliomaGE, tscapeBCa,tscapeMelanomaa, tscapeNSCLCa,tscapeOvariana

AMD1 adenosylmethionine decarboxylase 1 [Source:HGNC Symbol;Acc:457] locus=6:111195973-111216916 tscapeCRCd, tscapeOvariandAPBB1 amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65) [Source:HGNC Symbol;Acc:581]

locus=11:6416354-6440644tcgaGliomaGE, tscapeBCd

ARRB1 arrestin, beta 1 [Source:HGNC Symbol;Acc:711] locus=11:74975226-75062873 tcgaGliomaGEARRB2 arrestin, beta 2 [Source:HGNC Symbol;Acc:712] locus=17:4613784-4624795 snp3dMetastasis, tcgaGliomaGEASAH1 N-acylsphingosine amidohydrolase (acid ceramidase) 1 [Source:HGNC Symbol;Acc:735] locus=8:17913934-17942494 tcgaGliomaGEASAH2 N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2 [Source:HGNC Symbol;Acc:18860]

locus=10:51884446-52039568


19

http://www.ensembl.org/id/ENSG00000132356http://www.ensembl.org/id/ENSG00000131871http://www.ensembl.org/id/ENSG00000076555http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000123505http://www.ensembl.org/id/ENSG00000166313http://www.ensembl.org/id/ENSG00000137486http://www.ensembl.org/id/ENSG00000141480http://www.ensembl.org/id/ENSG00000104763http://www.ensembl.org/id/ENSG00000188611

name description studies

B3GNT6 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase) [Source:HGNC Symbol;Acc:24141]locus=11:76745385-76753096

tscapeOvariana

CNOT7 CCR4-NOT transcription complex, subunit 7 [Source:HGNC Symbol;Acc:14101] locus=8:17086737-17104387CNOT8 CCR4-NOT transcription complex, subunit 8 [Source:HGNC Symbol;Acc:9207] locus=5:154237113-154256353 tscapeRCCaCPT1A carnitine palmitoyltransferase 1A (liver) [Source:HGNC Symbol;Acc:2328] locus=11:68522088-68609399 tcgaBreastGE, tscapeSCLCaCPT1B carnitine palmitoyltransferase 1B (muscle) [Source:HGNC Symbol;Acc:2329] locus=22:51007290-51017899 tscapeBCd, tscapeHCCd,

tscapeNSCLCd, tscapeOvariand,tscapeSCLCd

CPT1C carnitine palmitoyltransferase 1C [Source:HGNC Symbol;Acc:18540] locus=19:50194373-50216988 tcgaGliomaGE, tscapeNSCLCd,tscapeOvariand

CYP17A1 cytochrome P450, family 17, subfamily A, polypeptide 1 [Source:HGNC Symbol;Acc:2593] locus=10:104590288-104597290 tscapeBCd, tscapeCRCd,tscapeOvariand

CYP1A1 cytochrome P450, family 1, subfamily A, polypeptide 1 [Source:HGNC Symbol;Acc:2595] locus=15:75011883-75017951 snp3dLungCCYP21A2 cytochrome P450, family 21, subfamily A, polypeptide 2 [Source:HGNC Symbol;Acc:2600] locus=6:32006042-32009447CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [Source:HGNC Symbol;Acc:2625] locus=22:42522501-42540472 tscapeGliomadCYP3A4 cytochrome P450, family 3, subfamily A, polypeptide 4 [Source:HGNC Symbol;Acc:2637] locus=7:99354604-99381888 tscapeNSCLCaCYP3A43 cytochrome P450, family 3, subfamily A, polypeptide 43 [Source:HGNC Symbol;Acc:17450] locus=7:99425636-99463718 tscapeNSCLCaCYP3A5 cytochrome P450, family 3, subfamily A, polypeptide 5 [Source:HGNC Symbol;Acc:2638] locus=7:99245817-99277621 tcgaBreastGE, tscapeNSCLCaCYP3A7 cytochrome P450, family 3, subfamily A, polypeptide 7 [Source:HGNC Symbol;Acc:2640] locus=7:99293368-99332819 tscapeNSCLCaGLI1 GLI family zinc finger 1 [Source:HGNC Symbol;Acc:4317] locus=12:57853918-57866045GLI2 GLI family zinc finger 2 [Source:HGNC Symbol;Acc:4318] locus=2:121493199-121750229 tcgaBreastGE, tscapeProstated,

tscapeRCCaGLI3 GLI family zinc finger 3 [Source:HGNC Symbol;Acc:4319] locus=7:42000548-42277469GUSB glucuronidase, beta [Source:HGNC Symbol;Acc:4696] locus=7:65425671-65447301 tcgaGliomaGEHSD17B2 hydroxysteroid (17-beta) dehydrogenase 2 [Source:HGNC Symbol;Acc:5211] locus=16:82068866-82132139HSD17B6 hydroxysteroid (17-beta) dehydrogenase 6 homolog (mouse) [Source:HGNC Symbol;Acc:23316] locus=12:57157108-57181574 tcgaBreastGE, tcgaGliomaGEHSD17B8 hydroxysteroid (17-beta) dehydrogenase 8 [Source:HGNC Symbol;Acc:3554] locus=6:33172419-33174608HSD3B1 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 [Source:HGNC Symbol;Acc:5217]

locus=1:120049821-120057681tscapeBCa, tscapeNSCLCd,tscapeSCLCd

HSD3B2 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 [Source:HGNC Symbol;Acc:5218]locus=1:119957554-119965658

tscapeBCa, tscapeNSCLCd,tscapeSCLCd

IDH3A isocitrate dehydrogenase 3 (NAD+) alpha [Source:HGNC Symbol;Acc:5384] locus=15:78441663-78464291 tcgaGliomaGEIDH3B isocitrate dehydrogenase 3 (NAD+) beta [Source:HGNC Symbol;Acc:5385] locus=20:2639041-2644865IDH3G isocitrate dehydrogenase 3 (NAD+) gamma [Source:HGNC Symbol;Acc:5386] locus=X:153051221-153059978 tcgaGliomaGE, tscapeBCa,

tscapeNSCLCaKL klotho [Source:HGNC Symbol;Acc:6344] locus=13:33590207-33640282 tcgaGliomaGE, tscapeBCd,

tscapeHCCd, tscapeOvariand,tscapeSCLCd

LRP5 low density lipoprotein receptor-related protein 5 [Source:HGNC Symbol;Acc:6697] locus=11:68080077-68216743 snp3dDiabetes, tcgaGliomaGE,tscapeSCLCa

LRP6 low density lipoprotein receptor-related protein 6 [Source:HGNC Symbol;Acc:6698] locus=12:12268959-12419946 cosmicMetastasis, tscapeProstatedMARCH6 membrane-associated ring finger (C3HC4) 6 [Source:HGNC Symbol;Acc:30550] locus=5:10353815-10435491 tcgaGliomaGENAE1 NEDD8 activating enzyme E1 subunit 1 [Source:HGNC Symbol;Acc:621] locus=16:66836778-66864900 tscapeOvariandPABPC1 poly(A) binding protein, cytoplasmic 1 [Source:HGNC Symbol;Acc:8554] locus=8:101698044-101735037 tcgaGliomaGE, tscapeNSCLCaPABPC1L poly(A) binding protein, cytoplasmic 1-like [Source:HGNC Symbol;Acc:15797] locus=20:43538703-43587676 tcgaGliomaGEPABPC1L2A poly(A) binding protein, cytoplasmic 1-like 2A [Source:HGNC Symbol;Acc:27989] locus=X:72297115-72299351 tcgaGliomaGEPABPC1L2B poly(A) binding protein, cytoplasmic 1-like 2B [Source:HGNC Symbol;Acc:31852] locus=X:72223352-72225551 tcgaBreastGEPABPC3 poly(A) binding protein, cytoplasmic 3 [Source:HGNC Symbol;Acc:8556] locus=13:25670300-25673389 tscapeBCd, tscapeHCCd,

tscapeSCLCdPABPC4 poly(A) binding protein, cytoplasmic 4 (inducible form) [Source:HGNC Symbol;Acc:8557] locus=1:40026488-40042462 tcgaGliomaGE, tscapeNSCLCa,

tscapeOvarianaPABPC4L poly(A) binding protein, cytoplasmic 4-like [Source:HGNC Symbol;Acc:31955] locus=4:135121062-135122903PABPC5 poly(A) binding protein, cytoplasmic 5 [Source:HGNC Symbol;Acc:13629] locus=X:90689594-90693583PIK3C2A phosphoinositide-3-kinase, class 2, alpha polypeptide [Source:HGNC Symbol;Acc:8971] locus=11:17099277-17229530 cosmicRecurrentPIK3C2B phosphoinositide-3-kinase, class 2, beta polypeptide [Source:HGNC Symbol;Acc:8972] locus=1:204391756-204463852 tcgaGliomaGE, tscapeBCa,

tscapeGliomaa, tscapeProstateaPIK3C2G phosphoinositide-3-kinase, class 2, gamma polypeptide [Source:HGNC Symbol;Acc:8973] locus=12:18400548-18801348 tscapeHCCdPIK3C3 phosphoinositide-3-kinase, class 3 [Source:HGNC Symbol;Acc:8974] locus=18:39535171-39667794PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide [Source:HGNC Symbol;Acc:8975] locus=3:178865902-178957881 cosmicPrimary, tcgaOvarianGE,

tscapeBCa, tscapeOvarianaPIK3CB phosphoinositide-3-kinase, catalytic, beta polypeptide [Source:HGNC Symbol;Acc:8976] locus=3:138372860-138553780 tcgaGliomaGEPIK3CD phosphoinositide-3-kinase, catalytic, delta polypeptide [Source:HGNC Symbol;Acc:8977] locus=1:9711790-9789172 tscapeBCd, tscapeCRCd,

tscapeHCCd, tscapeNSCLCd,tscapeOvariana, tscapeOvariand,tscapeRCCd

PIK3CG phosphoinositide-3-kinase, catalytic, gamma polypeptide [Source:HGNC Symbol;Acc:8978] locus=7:106505723-106547590 cosmicMetastasis, cosmicRecurrent,tcgaGliomaGE

PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [Source:HGNC Symbol;Acc:8979] locus=5:67511548-67597649 tcgaBreastGE, tcgaGliomaGE,tscapeBCd, tscapeCRCd,tscapeNSCLCd, tscapeOvariand,tscapeProstated, tscapeSCLCd

PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 (beta) [Source:HGNC Symbol;Acc:8980] locus=19:18263928-18281343 tcgaBreastGEPIK3R3 phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [Source:HGNC Symbol;Acc:8981] locus=1:46505812-46642160 tcgaBreastGE, tscapeSCLCaPIK3R5 phosphoinositide-3-kinase, regulatory subunit 5 [Source:HGNC Symbol;Acc:30035] locus=17:8782228-8869024 tcgaGliomaGEPIKFYVE phosphoinositide kinase, FYVE finger containing [Source:HGNC Symbol;Acc:23785] locus=2:209130991-209223475 tcgaOvarianGEPRKAA2 protein kinase, AMP-activated, alpha 2 catalytic subunit [Source:HGNC Symbol;Acc:9377] locus=1:57110995-57181008 tcgaGliomaGEPRKAB1 protein kinase, AMP-activated, beta 1 non-catalytic subunit [Source:HGNC Symbol;Acc:9378]

locus=12:120105558-120119435tcgaGliomaGE

PRKAB2 protein kinase, AMP-activated, beta 2 non-catalytic subunit [Source:HGNC Symbol;Acc:9379]locus=1:146626685-146644129

tscapeCRCa

PRKAG1 protein kinase, AMP-activated, gamma 1 non-catalytic subunit [Source:HGNC Symbol;Acc:9385]locus=12:49396058-49412592

tscapeRCCa


tcgaGliomaGE, tscapeMelanomaa,tscapeOvariana, tscapeOvariand


tscapeRCCd

SRM spermidine synthase [Source:HGNC Symbol;Acc:11296] locus=1:11114641-11120081 tscapeBCd, tscapeCRCd,tscapeHCCd, tscapeNSCLCd,tscapeOvariana, tscapeOvariand,tscapeRCCd

UGDH UDP-glucose 6-dehydrogenase [Source:HGNC Symbol;Acc:12525] locus=4:39500375-39529931 tcgaGliomaGE

Table 15: List of KEGG [2] pathways supporting the relationships between the genes shown in Figure 7. Number of edgestaken from each pathway is shown on edges column.

name edges genes

Steroid hormone biosynthesis 96 CYP11A1, CYP17A1, CYP1A1, CYP21A2, CYP3A4, CYP3A43, CYP3A5, CYP3A7, HSD17B2,HSD17B6, HSD17B8, HSD3B1, HSD3B2, UGT2B17, UGT2B28

Prostate cancer 78 AKT1, AKT2, AKT3, MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3,PIK3R5

Non-small cell lung cancer 72 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Melanoma 72 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Influenza A 72 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Measles 72 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Chagas disease (American trypanosomiasis) 72 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Neurotrophin signaling pathway 72 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Fc gamma R-mediated phagocytosis 72 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5VEGF signaling pathway 72 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Chemokine signaling pathway 72 AKT1, AKT2, AKT3, ARRB1, ARRB2, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2,

PIK3R3, PIK3R5Insulin signaling pathway 58 AC008810.1, ACACA, ACACB, AKT1, AKT2, AKT3, MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG,

PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3Acute myeloid leukemia 54 AKT1, AKT2, AKT3, MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3,

PIK3R5ErbB signaling pathway 54 AKT1, AKT2, AKT3, MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3,

PIK3R5Small cell lung cancer 48 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Chronic myeloid leukemia 48 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Cholinergic synapse 48 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5


20

http://www.ensembl.org/id/ENSG00000198488http://www.ensembl.org/id/ENSG00000198791http://www.ensembl.org/id/ENSG00000155508http://www.ensembl.org/id/ENSG00000110090http://www.ensembl.org/id/ENSG00000205560http://www.ensembl.org/id/ENSG00000169169http://www.ensembl.org/id/ENSG00000148795http://www.ensembl.org/id/ENSG00000140465http://www.ensembl.org/id/ENSG00000231852http://www.ensembl.org/id/ENSG00000100197http://www.ensembl.org/id/ENSG00000160868http://www.ensembl.org/id/ENSG00000021461http://www.ensembl.org/id/ENSG00000106258http://www.ensembl.org/id/ENSG00000160870http://www.ensembl.org/id/ENSG00000111087http://www.ensembl.org/id/ENSG00000074047http://www.ensembl.org/id/ENSG00000106571http://www.ensembl.org/id/ENSG00000169919http://www.ensembl.org/id/ENSG00000086696http://www.ensembl.org/id/ENSG00000025423http://www.ensembl.org/id/ENSG00000204228http://www.ensembl.org/id/ENSG00000203857http://www.ensembl.org/id/ENSG00000203859http://www.ensembl.org/id/ENSG00000166411http://www.ensembl.org/id/ENSG00000101365http://www.ensembl.org/id/ENSG00000067829http://www.ensembl.org/id/ENSG00000133116http://www.ensembl.org/id/ENSG00000162337http://www.ensembl.org/id/ENSG00000070018http://www.ensembl.org/id/ENSG00000145495http://www.ensembl.org/id/ENSG00000159593http://www.ensembl.org/id/ENSG00000070756http://www.ensembl.org/id/ENSG00000101104http://www.ensembl.org/id/ENSG00000186288http://www.ensembl.org/id/ENSG00000184388http://www.ensembl.org/id/ENSG00000151846http://www.ensembl.org/id/ENSG00000090621http://www.ensembl.org/id/ENSG00000254535http://www.ensembl.org/id/ENSG00000174740http://www.ensembl.org/id/ENSG00000011405http://www.ensembl.org/id/ENSG00000133056http://www.ensembl.org/id/ENSG00000139144http://www.ensembl.org/id/ENSG00000078142http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.ensembl.org/id/ENSG00000115020http://www.ensembl.org/id/ENSG00000162409http://www.ensembl.org/id/ENSG00000111725http://www.ensembl.org/id/ENSG00000131791http://www.ensembl.org/id/ENSG00000181929http://www.ensembl.org/id/ENSG00000106617http://www.ensembl.org/id/ENSG00000115592http://www.ensembl.org/id/ENSG00000116649http://www.ensembl.org/id/ENSG00000109814http://www.genome.jp/dbget-bin/www_bget?path:hsa00140http://www.ensembl.org/id/ENSG00000140459http://www.ensembl.org/id/ENSG00000148795http://www.ensembl.org/id/ENSG00000140465http://www.ensembl.org/id/ENSG00000231852http://www.ensembl.org/id/ENSG00000160868http://www.ensembl.org/id/ENSG00000021461http://www.ensembl.org/id/ENSG00000106258http://www.ensembl.org/id/ENSG00000160870http://www.ensembl.org/id/ENSG00000086696http://www.ensembl.org/id/ENSG00000025423http://www.ensembl.org/id/ENSG00000204228http://www.ensembl.org/id/ENSG00000203857http://www.ensembl.org/id/ENSG00000203859http://www.ensembl.org/id/ENSG00000197888http://www.ensembl.org/id/ENSG00000135226http://www.genome.jp/dbget-bin/www_bget?path:hsa05215http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000198793http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa05223http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa05218http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa05164http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa05162http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa05142http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa04722http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa04666http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa04370http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa04062http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000137486http://www.ensembl.org/id/ENSG00000141480http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa04910http://www.ensembl.org/id/ENSG00000132356http://www.ensembl.org/id/ENSG00000132142http://www.ensembl.org/id/ENSG00000076555http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000198793http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.ensembl.org/id/ENSG00000162409http://www.ensembl.org/id/ENSG00000111725http://www.ensembl.org/id/ENSG00000131791http://www.ensembl.org/id/ENSG00000181929http://www.ensembl.org/id/ENSG00000106617http://www.ensembl.org/id/ENSG00000115592http://www.genome.jp/dbget-bin/www_bget?path:hsa05221http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000198793http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa04012http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000198793http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa05222http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa05220http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa04725http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506

name edges genes

T cell receptor signaling pathway 48 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Focal adhesion 48 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5RNA degradation 36 BTG1, CNOT7, CNOT8, PABPC1, PABPC1L, PABPC1L2A, PABPC1L2B, PABPC3, PABPC4,

PABPC4L, PABPC5Adipocytokine signaling pathway 33 AC008810.1, ACACB, ACSL3, AKT1, AKT2, AKT3, CAMKK2, CPT1A, CPT1B, CPT1C, MTOR,

PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3Colorectal cancer 24 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Jak-STAT signaling pathway 24 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Osteoclast differentiation 24 AKT1, AKT2, AKT3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5Drug metabolism - cytochrome P450 20 CYP2D6, CYP3A4, CYP3A43, CYP3A5, CYP3A7, UGT2B17, UGT2B28Phosphatidylinositol signaling system 18 INPP4B, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1,

PIK3R2, PIK3R3, PIK3R5, PIKFYVERetinol metabolism 18 CYP1A1, CYP3A4, CYP3A43, CYP3A5, CYP3A7, UGT2B17, UGT2B28Pathways in cancer 12 AKT1, AKT2, AKT3, FZD2, GLI1, GLI2, GLI3, MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG,

PIK3R1, PIK3R2, PIK3R3, PIK3R5, WNT5ABasal cell carcinoma 10 FZD2, GLI1, GLI2, GLI3, WNT5AHedgehog signaling pathway 9 GLI1, GLI2, GLI3, WNT5A, ZIC2mTOR signaling pathway 7 AC008810.1, AKT1, AKT2, AKT3, MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2,

PIK3R3, PIK3R5, PRKAA2Sphingolipid metabolism 7 ASAH1, ASAH2, DEGS2, SMPD2Glioma 6 AKT1, AKT2, AKT3, MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3,

PIK3R5Inositol phosphate metabolism 6 INPP4B, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIKFYVEStarch and sucrose metabolism 6 GUSB, KL, UGDH, UGT2B17, UGT2B28Pentose and glucuronate interconversions 6 GUSB, KL, UGDH, UGT2B17, UGT2B28Citrate cycle (TCA cycle) 6 IDH1, IDH3A, IDH3B, IDH3GWnt signaling pathway 5 FZD2, LRP5, LRP6, WNT5AAlzheimer’s disease 4 APBB1, APP, NAE1Endocytosis 4 ADRB2, ARRB1, ARRB2Protein processing in endoplasmic reticulum 4 AC023024.1, MARCH6, UBE2G1Arginine and proline metabolism 4 AMD1, SMS, SRMMucin type O-Glycan biosynthesis 3 B3GNT6, GALNTL4, ST6GALNAC1Fatty acid metabolism 3 ACSL3, CPT1A, CPT1B, CPT1CMelanogenesis 2 FZD2, WNT5ADrug metabolism - other enzymes 2 CYP3A4, CYP3A43, CYP3A5, CYP3A7, GUSB, UGT2B17, UGT2B28Porphyrin and chlorophyll metabolism 2 GUSB, UGT2B17, UGT2B28Cysteine and methionine metabolism 2 AMD1, SMS, SRMFatty acid biosynthesis 2 ACACA, ACACBEndocrine and other factor-regulated calciumreabsorption

1 ATP1B1, KL

Glutathione metabolism 1 IDH1, SMS, SRM

21

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ttp://www.ensembl.org/id/ENSG00000197888http://www.ensembl.org/id/ENSG00000135226http://www.genome.jp/dbget-bin/www_bget?path:hsa05200http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000180340http://www.ensembl.org/id/ENSG00000111087http://www.ensembl.org/id/ENSG00000074047http://www.ensembl.org/id/ENSG00000106571http://www.ensembl.org/id/ENSG00000198793http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.ensembl.org/id/ENSG00000114251http://www.genome.jp/dbget-bin/www_bget?path:hsa05217http://www.ensembl.org/id/ENSG00000180340http://www.ensembl.org/id/ENSG00000111087http://www.ensembl.org/id/ENSG00000074047http://www.ensembl.org/id/ENSG00000106571http://www.ensembl.org/id/ENSG00000114251http://www.genome.jp/dbget-bin/www_bget?path:hsa04340http://www.ensembl.org/id/ENSG00000111087http://www.ensembl.org/id/ENSG00000074047http://www.ensembl.org/id/ENSG00000106571http://www.ensembl.org/id/ENSG00000114251http://www.ensembl.org/id/ENSG00000043355http://www.genome.jp/dbget-bin/www_bget?path:hsa04150http://www.ensembl.org/id/ENSG00000132356http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000198793http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.ensembl.org/id/ENSG00000162409http://www.genome.jp/dbget-bin/www_bget?path:hsa00600http://www.ensembl.org/id/ENSG00000104763http://www.ensembl.org/id/ENSG00000188611http://www.ensembl.org/id/ENSG00000168350http://www.ensembl.org/id/ENSG00000135587http://www.genome.jp/dbget-bin/www_bget?path:hsa05214http://www.ensembl.org/id/ENSG00000142208http://www.ensembl.org/id/ENSG00000105221http://www.ensembl.org/id/ENSG00000117020http://www.ensembl.org/id/ENSG00000198793http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000145675http://www.ensembl.org/id/ENSG00000105647http://www.ensembl.org/id/ENSG00000117461http://www.ensembl.org/id/ENSG00000141506http://www.genome.jp/dbget-bin/www_bget?path:hsa00562http://www.ensembl.org/id/ENSG00000109452http://www.ensembl.org/id/ENSG00000011405http://www.ensembl.org/id/ENSG00000133056http://www.ensembl.org/id/ENSG00000139144http://www.ensembl.org/id/ENSG00000078142http://www.ensembl.org/id/ENSG00000121879http://www.ensembl.org/id/ENSG00000051382http://www.ensembl.org/id/ENSG00000171608http://www.ensembl.org/id/ENSG00000105851http://www.ensembl.org/id/ENSG00000115020http://www.genome.jp/dbget-bin/www_bget?path:hsa00500http://www.ensembl.org/id/ENSG00000169919http://www.ensembl.org/id/ENSG00000133116http://www.ensembl.org/id/ENSG00000109814http://www.ensembl.org/id/ENSG00000197888http://www.ensembl.org/id/ENSG00000135226http://www.genome.jp/dbget-bin/www_bget?path:hsa00040http://www.ensembl.org/id/ENSG00000169919http://www.ensembl.org/id/ENSG00000133116http://www.ensembl.org/id/ENSG00000109814http://www.ensembl.org/id/ENSG00000197888http://www.ensembl.org/id/ENSG00000135226http://www.genome.jp/dbget-bin/www_bget?path:hsa00020http://www.ensembl.org/id/ENSG00000138413http://www.ensembl.org/id/ENSG00000166411http://www.ensembl.org/id/ENSG00000101365http://www.ensembl.org/id/ENSG00000067829http://www.genome.jp/dbget-bin/www_bget?path:hsa04310http://www.ensembl.org/id/ENSG00000180340http://www.ensembl.org/id/ENSG00000162337http://www.ensembl.org/id/ENSG00000070018http://www.ensembl.org/id/ENSG00000114251http://www.genome.jp/dbget-bin/www_bget?path:hsa05010http://www.ensembl.org/id/ENSG00000166313http://www.ensembl.org/id/ENSG00000142192http://www.ensembl.org/id/ENSG00000159593http://www.genome.jp/dbget-bin/www_bget?path:hsa04144http://www.ensembl.org/id/ENSG00000169252http://www.ensembl.org/id/ENSG00000137486http://www.ensembl.org/id/ENSG00000141480http://www.genome.jp/dbget-bin/www_bget?path:hsa04141http://www.ensembl.org/id/ENSG00000131871http://www.ensembl.org/id/ENSG00000145495http://www.ensembl.org/id/ENSG00000132388http://www.genome.jp/dbget-bin/www_bget?path:hsa00330http://www.ensembl.org/id/ENSG00000123505http://www.ensembl.org/id/ENSG00000102172http://www.ensembl.org/id/ENSG00000116649http://www.genome.jp/dbget-bin/www_bget?path:hsa00512http://www.ensembl.org/id/ENSG00000198488http://www.ensembl.org/id/ENSG00000110328http://www.ensembl.org/id/ENSG00000070526http://www.genome.jp/dbget-bin/www_bget?path:hsa00071http://www.ensembl.org/id/ENSG00000123983http://www.ensembl.org/id/ENSG00000110090http://www.ensembl.org/id/ENSG00000205560http://www.ensembl.org/id/ENSG00000169169http://www.genome.jp/dbget-bin/www_bget?path:hsa04916http://www.ensembl.org/id/ENSG00000180340http://www.ensembl.org/id/ENSG00000114251http://www.genome.jp/dbget-bin/www_bget?path:hsa00983http://www.ensembl.org/id/ENSG00000160868http://www.ensembl.org/id/ENSG00000021461http://www.ensembl.org/id/ENSG00000106258http://www.ensembl.org/id/ENSG00000160870http://www.ensembl.org/id/ENSG00000169919http://www.ensembl.org/id/ENSG00000197888http://www.ensembl.org/id/ENSG00000135226http://www.genome.jp/dbget-bin/www_bget?path:hsa00860http://www.ensembl.org/id/ENSG00000169919http://www.ensembl.org/id/ENSG00000197888http://www.ensembl.org/id/ENSG00000135226http://www.genome.jp/dbget-bin/www_bget?path:hsa00270http://www.ensembl.org/id/ENSG00000123505http://www.ensembl.org/id/ENSG00000102172http://www.ensembl.org/id/ENSG00000116649http://www.genome.jp/dbget-bin/www_bget?path:hsa00061http://www.ensembl.org/id/ENSG00000132142http://www.ensembl.org/id/ENSG00000076555http://www.genome.jp/dbget-bin/www_bget?path:hsa04961http://www.genome.jp/dbget-bin/www_bget?path:hsa04961http://www.ensembl.org/id/ENSG00000143153http://www.ensembl.org/id/ENSG00000133116http://www.genome.jp/dbget-bin/www_bget?path:hsa00480http://www.ensembl.org/id/ENSG00000138413http://www.ensembl.org/id/ENSG00000102172http://www.ensembl.org/id/ENSG00000116649

9.1.1 GO enrichment of the candidate pathway

Table 16: Enriched Gene Ontology terms [1] (FDR corrected p ≤ 0.01). Ratio is the proportion of the annotated genes amongthe whole gene set. List is sorted based on the FDR corrected p-values. Green and blue borders are referring to up and downregulated genes, respectively.

Ratio Type Description Genes

0.500 BP lipid metabolic process AC008810.1, ACACA, ACACB, ACSL3, AKT1, AKT2, ASAH1, ASAH2, CPT1A, CPT1B, CPT1C,CYP11A1, CYP17A1, CYP1A1, CYP21A2, CYP2D6, CYP3A4, CYP3A5, DEGS2, HSD17B2, HSD17B6,HSD17B8, HSD3B1, HSD3B2, IDH1, MTOR, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB,PIK3CD, PIK3CG, PIK3R1, PIKFYVE, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3,SMPD2, UGT2B17

0.250 BP lipid modification AC008810.1, ACACB, AKT1, AKT2, CPT1A, CPT1B, MTOR, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3,PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2,PRKAG3

0.138 CC phosphatidylinositol 3-kinase complex MTOR, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2,PIK3R3

0.148 BP regulation of fatty acid oxidation AC008810.1, ACACB, AKT1, AKT2, CPT1A, CPT1B, MTOR, PRKAA2, PRKAB1, PRKAB2, PRKAG1,PRKAG2, PRKAG3

0.109 MF 1-phosphatidylinositol-3-kinase activity PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R2, PIK3R30.375 BP cellular response to chemical stimulus AC008810.1, AC023024.1, AKT1, AKT2, ARRB2, CYP11A1, CYP17A1, CYP1A1, CYP2D6, CYP3A4,

CYP3A43, CYP3A5, CYP3A7, FZD2, GLI2, KL, LRP6, MTOR, PIK3C3, PIK3CA, PIK3CB, PIK3R1,PIK3R2, PIK3R3, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3, UGDH, UGT2B28,WNT5A

0.193 BP insulin receptor signaling pathway AC008810.1, AKT1, AKT2, KL, MTOR, PIK3C3, PIK3CA, PIK3CB, PIK3R1, PIK3R2, PIK3R3, PRKAA2,PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3

0.368 CC cell fraction ACACA, ACSL3, ADRB2, AKT1, AKT2, APP, ARRB1, CPT1A, CPT1B, CYP1A1, CYP2D6, CYP3A4,CYP3A43, CYP3A5, CYP3A7, GLI2, GUSB, HSD17B6, HSD17B8, HSD3B1, HSD3B2, IDH1, KL, LRP6,MTOR, NAE1, PIK3C2B, PIK3R1, SMPD2,

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