Correlation between gene mutation status and selected clinical features
Overview
Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.

Summary

Testing the association between mutation status of 110 genes and 5 clinical features across 269 patients, 5 significant findings detected with Q value < 0.25.

  • IDH1 mutation correlated to 'AGE'.

  • PRB2 mutation correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

  • OR5W2 mutation correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

  • OR5P2 mutation correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

  • SHB mutation correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 110 genes and 5 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 5 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER KARNOFSKY
PERFORMANCE
SCORE 		RADIATIONS
RADIATION
REGIMENINDICATION
nMutated (%) nWild-Type logrank test t-test Fisher's exact test t-test Fisher's exact test
IDH1 13 (5%) 256 0.00204
(1.00) 		0.000245
(0.131) 		0.386
(1.00) 		0.0655
(1.00) 		0.00514
(1.00)
PRB2 5 (2%) 264 0.918
(1.00) 		0.167
(1.00) 		1
(1.00) 		0.000423
(0.226) 		1
(1.00)
OR5W2 5 (2%) 264 0.394
(1.00) 		0.0763
(1.00) 		1
(1.00) 		0.000424
(0.226) 		0.166
(1.00)
OR5P2 4 (1%) 265 0.265
(1.00) 		0.12
(1.00) 		0.3
(1.00) 		0.000423
(0.226) 		0.613
(1.00)
SHB 3 (1%) 266 0.978
(1.00) 		0.621
(1.00) 		0.301
(1.00) 		0.000424
(0.226) 		0.554
(1.00)
PIK3R1 31 (12%) 238 0.747
(1.00) 		0.596
(1.00) 		0.431
(1.00) 		0.872
(1.00) 		0.551
(1.00)
BRAF 4 (1%) 265 0.242
(1.00) 		0.198
(1.00) 		1
(1.00) 		0.158
(1.00) 		0.124
(1.00)
EGFR 72 (27%) 197 0.791
(1.00) 		0.485
(1.00) 		0.254
(1.00) 		0.512
(1.00) 		0.665
(1.00)
PTEN 85 (32%) 184 0.632
(1.00) 		0.195
(1.00) 		0.588
(1.00) 		0.98
(1.00) 		0.0542
(1.00)
TP53 77 (29%) 192 0.0321
(1.00) 		0.159
(1.00) 		0.674
(1.00) 		0.00657
(1.00) 		0.322
(1.00)
PIK3CA 28 (10%) 241 0.577
(1.00) 		0.854
(1.00) 		0.836
(1.00) 		0.98
(1.00) 		0.534
(1.00)
RB1 22 (8%) 247 0.104
(1.00) 		0.822
(1.00) 		0.818
(1.00) 		0.0179
(1.00) 		0.492
(1.00)
NF1 28 (10%) 241 0.845
(1.00) 		0.289
(1.00) 		1
(1.00) 		0.18
(1.00) 		0.677
(1.00)
SPTA1 26 (10%) 243 0.533
(1.00) 		0.176
(1.00) 		0.29
(1.00) 		0.469
(1.00) 		0.279
(1.00)
KRTAP4-11 9 (3%) 260 0.627
(1.00) 		0.406
(1.00) 		0.728
(1.00) 		0.818
(1.00) 		0.724
(1.00)
GABRA6 11 (4%) 258 0.912
(1.00) 		0.22
(1.00) 		1
(1.00) 		0.607
(1.00) 		1
(1.00)
KEL 15 (6%) 254 0.512
(1.00) 		0.404
(1.00) 		0.417
(1.00) 		0.0925
(1.00) 		0.404
(1.00)
CDH18 11 (4%) 258 0.379
(1.00) 		0.527
(1.00) 		1
(1.00) 		0.567
(1.00) 		0.523
(1.00)
RPL5 7 (3%) 262 0.994
(1.00) 		0.784
(1.00) 		0.261
(1.00) 		0.558
(1.00) 		0.427
(1.00)
SEMA3C 11 (4%) 258 0.0541
(1.00) 		0.959
(1.00) 		0.751
(1.00) 		0.77
(1.00) 		0.2
(1.00)
TPTE2 8 (3%) 261 0.256
(1.00) 		0.585
(1.00) 		1
(1.00) 		0.0232
(1.00) 		0.456
(1.00)
ZNF844 6 (2%) 263 0.579
(1.00) 		0.821
(1.00) 		0.195
(1.00) 		0.872
(1.00) 		1
(1.00)
OR8K3 6 (2%) 263 0.695
(1.00) 		0.904
(1.00) 		0.421
(1.00) 		0.544
(1.00) 		0.668
(1.00)
OR5AR1 6 (2%) 263 0.426
(1.00) 		0.0071
(1.00) 		0.671
(1.00) 		0.0605
(1.00) 		0.424
(1.00)
STAG2 12 (4%) 257 0.0148
(1.00) 		0.949
(1.00) 		0.763
(1.00) 		0.0956
(1.00) 		0.353
(1.00)
SEMG1 8 (3%) 261 0.941
(1.00) 		0.142
(1.00) 		0.715
(1.00) 		0.33
(1.00) 		0.132
(1.00)
CDC27 5 (2%) 264 0.209
(1.00) 		0.69
(1.00) 		0.358
(1.00) 		1
(1.00)
PDGFRA 11 (4%) 258 0.59
(1.00) 		0.0282
(1.00) 		1
(1.00) 		0.719
(1.00) 		0.523
(1.00)
ADAM29 9 (3%) 260 0.668
(1.00) 		0.0551
(1.00) 		0.162
(1.00) 		0.825
(1.00) 		0.502
(1.00)
SULT1B1 6 (2%) 263 0.0779
(1.00) 		0.984
(1.00) 		1
(1.00) 		0.825
(1.00) 		1
(1.00)
ABCC9 11 (4%) 258 0.968
(1.00) 		0.267
(1.00) 		0.216
(1.00) 		0.52
(1.00) 		0.523
(1.00)
NLRP5 12 (4%) 257 0.334
(1.00) 		0.964
(1.00) 		0.545
(1.00) 		0.0655
(1.00) 		1
(1.00)
LZTR1 10 (4%) 259 0.705
(1.00) 		0.285
(1.00) 		0.0989
(1.00) 		0.77
(1.00) 		0.326
(1.00)
CALCR 7 (3%) 262 0.0298
(1.00) 		0.0162
(1.00) 		1
(1.00) 		0.718
(1.00) 		1
(1.00)
QKI 5 (2%) 264 0.92
(1.00) 		0.813
(1.00) 		1
(1.00) 		0.527
(1.00) 		0.0521
(1.00)
ZPBP 5 (2%) 264 0.35
(1.00) 		0.994
(1.00) 		0.358
(1.00) 		0.872
(1.00) 		0.347
(1.00)
PSPH 5 (2%) 264 0.207
(1.00) 		0.374
(1.00) 		0.656
(1.00) 		0.932
(1.00) 		0.661
(1.00)
UGT2A3 6 (2%) 263 0.969
(1.00) 		0.841
(1.00) 		1
(1.00) 		0.872
(1.00) 		0.0945
(1.00)
WNT2 5 (2%) 264 0.36
(1.00) 		0.244
(1.00) 		0.0606
(1.00) 		0.685
(1.00) 		1
(1.00)
OR5D18 6 (2%) 263 0.174
(1.00) 		0.716
(1.00) 		0.671
(1.00) 		0.179
(1.00) 		1
(1.00)
ABCB1 10 (4%) 259 0.498
(1.00) 		0.11
(1.00) 		0.177
(1.00) 		0.455
(1.00) 		0.326
(1.00)
COL1A2 10 (4%) 259 0.751
(1.00) 		0.108
(1.00) 		1
(1.00) 		0.983
(1.00) 		0.326
(1.00)
ATRX 15 (6%) 254 0.045
(1.00) 		0.000576
(0.305) 		0.417
(1.00) 		0.0429
(1.00) 		0.0945
(1.00)
C1ORF150 3 (1%) 266 0.67
(1.00) 		0.0936
(1.00) 		1
(1.00) 		0.24
(1.00) 		1
(1.00)
LRRC55 6 (2%) 263 0.0165
(1.00) 		0.518
(1.00) 		0.671
(1.00) 		0.0451
(1.00) 		1
(1.00)
DCAF12L2 8 (3%) 261 0.536
(1.00) 		0.691
(1.00) 		0.265
(1.00) 		0.713
(1.00) 		1
(1.00)
LRFN5 7 (3%) 262 0.0282
(1.00) 		0.412
(1.00) 		0.261
(1.00) 		0.331
(1.00) 		0.00817
(1.00)
LUM 4 (1%) 265 0.0891
(1.00) 		0.845
(1.00) 		1
(1.00) 		0.752
(1.00) 		0.613
(1.00)
MMP13 6 (2%) 263 0.608
(1.00) 		0.157
(1.00) 		1
(1.00) 		0.0258
(1.00) 		0.0945
(1.00)
HEATR7B2 11 (4%) 258 0.885
(1.00) 		0.0614
(1.00) 		0.751
(1.00) 		0.979
(1.00) 		0.2
(1.00)
UGT2B28 6 (2%) 263 0.774
(1.00) 		0.828
(1.00) 		0.421
(1.00) 		0.804
(1.00) 		1
(1.00)
OR5D13 5 (2%) 264 0.461
(1.00) 		0.427
(1.00) 		0.656
(1.00) 		0.661
(1.00)
ZNF99 6 (2%) 263 0.752
(1.00) 		0.759
(1.00) 		0.421
(1.00) 		0.824
(1.00) 		1
(1.00)
SLC5A7 6 (2%) 263 0.128
(1.00) 		0.675
(1.00) 		0.421
(1.00) 		0.33
(1.00) 		1
(1.00)
SEMA3E 7 (3%) 262 0.396
(1.00) 		0.661
(1.00) 		1
(1.00) 		0.544
(1.00) 		0.1
(1.00)
TCHH 16 (6%) 253 0.351
(1.00) 		0.337
(1.00) 		0.427
(1.00) 		0.472
(1.00) 		0.188
(1.00)
SLC26A3 6 (2%) 263 0.497
(1.00) 		0.345
(1.00) 		0.421
(1.00) 		0.544
(1.00) 		0.668
(1.00)
GABRB2 6 (2%) 263 0.274
(1.00) 		0.0308
(1.00) 		0.195
(1.00) 		0.372
(1.00) 		0.188
(1.00)
CFHR4 5 (2%) 264 0.371
(1.00) 		0.996
(1.00) 		0.358
(1.00) 		0.977
(1.00) 		1
(1.00)
IL18RAP 5 (2%) 264 0.778
(1.00) 		0.195
(1.00) 		0.358
(1.00) 		0.294
(1.00) 		0.661
(1.00)
OGDH 3 (1%) 266 0.245
(1.00) 		0.317
(1.00) 		1
(1.00) 		0.297
(1.00) 		1
(1.00)
PCDH11X 8 (3%) 261 0.0982
(1.00) 		0.161
(1.00) 		0.468
(1.00) 		0.0237
(1.00) 		0.132
(1.00)
SPRYD5 6 (2%) 263 0.8
(1.00) 		0.821
(1.00) 		0.671
(1.00) 		0.544
(1.00) 		1
(1.00)
TGFA 4 (1%) 265 0.907
(1.00) 		0.378
(1.00) 		0.139
(1.00) 		1
(1.00)
UGT2B4 5 (2%) 264 0.348
(1.00) 		0.656
(1.00) 		0.656
(1.00) 		0.138
(1.00) 		0.347
(1.00)
FOXR2 5 (2%) 264 0.202
(1.00) 		0.957
(1.00) 		1
(1.00) 		0.872
(1.00) 		1
(1.00)
PSG8 6 (2%) 263 0.277
(1.00) 		0.479
(1.00) 		0.195
(1.00) 		0.865
(1.00) 		0.424
(1.00)
CNTNAP2 12 (4%) 257 0.818
(1.00) 		0.143
(1.00) 		0.364
(1.00) 		0.157
(1.00) 		1
(1.00)
PIK3C2G 9 (3%) 260 0.124
(1.00) 		0.411
(1.00) 		0.293
(1.00) 		0.544
(1.00) 		0.285
(1.00)
SCN9A 11 (4%) 258 0.0299
(1.00) 		0.26
(1.00) 		0.751
(1.00) 		0.255
(1.00) 		0.2
(1.00)
GABRA1 5 (2%) 264 0.788
(1.00) 		0.913
(1.00) 		0.656
(1.00) 		0.24
(1.00) 		1
(1.00)
DYNC1I1 7 (3%) 262 0.0997
(1.00) 		0.429
(1.00) 		1
(1.00) 		0.0853
(1.00) 		0.698
(1.00)
PODXL 3 (1%) 266 0.355
(1.00) 		0.224
(1.00) 		0.301
(1.00) 		0.126
(1.00) 		0.554
(1.00)
HCN1 10 (4%) 259 0.179
(1.00) 		0.837
(1.00) 		1
(1.00) 		0.158
(1.00) 		0.103
(1.00)
POTEF 5 (2%) 264 0.969
(1.00) 		0.702
(1.00) 		1
(1.00) 		1
(1.00)
CXORF22 8 (3%) 261 0.903
(1.00) 		0.548
(1.00) 		0.145
(1.00) 		0.455
(1.00) 		0.268
(1.00)
AFM 6 (2%) 263 0.277
(1.00) 		0.407
(1.00) 		0.671
(1.00) 		0.378
(1.00) 		1
(1.00)
KRTAP20-2 3 (1%) 266 0.519
(1.00) 		0.338
(1.00) 		1
(1.00) 		0.554
(1.00)
OTC 3 (1%) 266 0.123
(1.00) 		0.764
(1.00) 		0.301
(1.00) 		0.28
(1.00)
TRAT1 4 (1%) 265 0.141
(1.00) 		0.471
(1.00) 		1
(1.00) 		0.613
(1.00)
KLK6 3 (1%) 266 0.241
(1.00) 		0.221
(1.00) 		0.301
(1.00) 		0.554
(1.00)
OR4D5 4 (1%) 265 0.654
(1.00) 		0.0843
(1.00) 		0.3
(1.00) 		0.837
(1.00) 		0.124
(1.00)
GPX5 3 (1%) 266 0.356
(1.00) 		0.232
(1.00) 		1
(1.00) 		0.554
(1.00)
KRTAP4-7 3 (1%) 266 0.459
(1.00) 		0.317
(1.00) 		0.556
(1.00) 		0.28
(1.00)
CDH9 8 (3%) 261 0.534
(1.00) 		0.579
(1.00) 		0.468
(1.00) 		0.482
(1.00) 		1
(1.00)
CDHR3 3 (1%) 266 0.264
(1.00) 		0.553
(1.00) 		1
(1.00) 		0.294
(1.00) 		0.554
(1.00)
OR4P4 4 (1%) 265 0.952
(1.00) 		0.364
(1.00) 		1
(1.00) 		1
(1.00)
OR52M1 4 (1%) 265 0.969
(1.00) 		0.465
(1.00) 		1
(1.00) 		0.752
(1.00) 		1
(1.00)
KLF17 5 (2%) 264 0.00262
(1.00) 		0.306
(1.00) 		0.162
(1.00) 		0.469
(1.00) 		1
(1.00)
OR8J3 4 (1%) 265 0.384
(1.00) 		0.573
(1.00) 		0.624
(1.00) 		0.644
(1.00) 		0.301
(1.00)
AP3S1 3 (1%) 266 0.239
(1.00) 		0.348
(1.00) 		0.556
(1.00) 		0.24
(1.00) 		0.554
(1.00)
ST6GAL2 5 (2%) 264 0.884
(1.00) 		0.342
(1.00) 		0.0606
(1.00) 		0.0858
(1.00) 		0.661
(1.00)
CD3EAP 3 (1%) 266 0.857
(1.00) 		0.668
(1.00) 		1
(1.00) 		0.738
(1.00) 		1
(1.00)
F9 4 (1%) 265 0.0233
(1.00) 		0.541
(1.00) 		0.624
(1.00) 		1
(1.00)
DPP10 7 (3%) 262 0.585
(1.00) 		0.442
(1.00) 		0.261
(1.00) 		0.24
(1.00) 		1
(1.00)
TCN1 4 (1%) 265 0.907
(1.00) 		0.322
(1.00) 		0.624
(1.00) 		0.124
(1.00)
TRPV6 7 (3%) 262 0.822
(1.00) 		0.0725
(1.00) 		0.708
(1.00) 		0.825
(1.00) 		0.1
(1.00)
PAN3 6 (2%) 263 0.289
(1.00) 		0.462
(1.00) 		1
(1.00) 		0.777
(1.00) 		0.668
(1.00)
CDKN2C 3 (1%) 266 0.733
(1.00) 		0.559
(1.00) 		0.556
(1.00) 		1
(1.00)
AZGP1 4 (1%) 265 0.643
(1.00) 		0.822
(1.00) 		1
(1.00) 		1
(1.00)
DRD5 7 (3%) 262 0.63
(1.00) 		0.241
(1.00) 		1
(1.00) 		0.294
(1.00) 		1
(1.00)
FGA 6 (2%) 263 0.927
(1.00) 		0.369
(1.00) 		0.0893
(1.00) 		0.372
(1.00) 		0.668
(1.00)
FGG 5 (2%) 264 0.41
(1.00) 		0.074
(1.00) 		0.358
(1.00) 		0.294
(1.00) 		0.661
(1.00)
OR10G8 4 (1%) 265 0.877
(1.00) 		0.262
(1.00) 		0.624
(1.00) 		0.872
(1.00) 		0.613
(1.00)
PCMTD1 3 (1%) 266 0.874
(1.00) 		0.672
(1.00) 		0.556
(1.00) 		0.556
(1.00) 		0.554
(1.00)
PROKR2 6 (2%) 263 0.46
(1.00) 		0.0205
(1.00) 		1
(1.00) 		0.992
(1.00) 		0.668
(1.00)
CYP3A5 5 (2%) 264 0.349
(1.00) 		0.715
(1.00) 		0.358
(1.00) 		0.378
(1.00) 		1
(1.00)
FRMD7 6 (2%) 263 0.716
(1.00) 		0.583
(1.00) 		1
(1.00) 		0.908
(1.00) 		1
(1.00)
KCNB2 5 (2%) 264 0.357
(1.00) 		0.666
(1.00) 		0.358
(1.00) 		0.0521
(1.00)
KDR 7 (3%) 262 0.352
(1.00) 		0.775
(1.00) 		0.428
(1.00) 		0.877
(1.00) 		0.427
(1.00)
'IDH1 MUTATION STATUS' versus 'AGE'

P value = 0.000245 (t-test), Q value = 0.13

Table S1.  Gene #4: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 269 61.2 (12.6)
IDH1 MUTATED 13 41.5 (14.7)
IDH1 WILD-TYPE 256 62.2 (11.6)

Figure S1.  Get High-res Image Gene #4: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'PRB2 MUTATION STATUS' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 0.000423 (t-test), Q value = 0.23

Table S2.  Gene #15: 'PRB2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 194 75.9 (16.0)
PRB2 MUTATED 4 80.0 (0.0)
PRB2 WILD-TYPE 190 75.8 (16.2)

Figure S2.  Get High-res Image Gene #15: 'PRB2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

'OR5W2 MUTATION STATUS' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 0.000424 (t-test), Q value = 0.23

Table S3.  Gene #38: 'OR5W2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 194 75.9 (16.0)
OR5W2 MUTATED 3 80.0 (0.0)
OR5W2 WILD-TYPE 191 75.8 (16.1)

Figure S3.  Get High-res Image Gene #38: 'OR5W2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

'OR5P2 MUTATION STATUS' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 0.000423 (t-test), Q value = 0.23

Table S4.  Gene #63: 'OR5P2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 194 75.9 (16.0)
OR5P2 MUTATED 4 80.0 (0.0)
OR5P2 WILD-TYPE 190 75.8 (16.2)

Figure S4.  Get High-res Image Gene #63: 'OR5P2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

'SHB MUTATION STATUS' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 0.000424 (t-test), Q value = 0.23

Table S5.  Gene #106: 'SHB MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 194 75.9 (16.0)
SHB MUTATED 3 80.0 (0.0)
SHB WILD-TYPE 191 75.8 (16.1)

Figure S5.  Get High-res Image Gene #106: 'SHB MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

Methods & Data
Input

  • Mutation data file = GBM-TP.mutsig.cluster.txt

  • Clinical data file = GBM-TP.clin.merged.picked.txt

  • Number of patients = 269

  • Number of significantly mutated genes = 110

  • Number of selected clinical features = 5

  • Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' function in R

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

References
[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)
[4] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)
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