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 149 genes and 3 clinical features across 139 patients, 2 significant findings detected with Q value < 0.25.

  • MUC7 mutation correlated to 'AGE'.

  • KRT26 mutation correlated to 'Time to Death'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 149 genes and 3 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER
nMutated (%) nWild-Type logrank test t-test Fisher's exact test
MUC7 11 (8%) 128 0.495
(1.00) 		0.000211
(0.0941) 		0.746
(1.00)
KRT26 7 (5%) 132 6.86e-06
(0.00307) 		0.741
(1.00) 		1
(1.00)
BRAF 69 (50%) 70 0.123
(1.00) 		0.0503
(1.00) 		1
(1.00)
NRAS 43 (31%) 96 0.8
(1.00) 		0.164
(1.00) 		0.85
(1.00)
CDKN2A 21 (15%) 118 0.638
(1.00) 		0.532
(1.00) 		1
(1.00)
TP53 25 (18%) 114 0.464
(1.00) 		0.0985
(1.00) 		0.819
(1.00)
PTEN 9 (6%) 130 0.857
(1.00) 		0.798
(1.00) 		0.725
(1.00)
ACSM2B 28 (20%) 111 0.146
(1.00) 		0.952
(1.00) 		0.00764
(1.00)
LCE1B 9 (6%) 130 0.586
(1.00) 		0.671
(1.00) 		0.725
(1.00)
CADM2 15 (11%) 124 0.792
(1.00) 		0.888
(1.00) 		1
(1.00)
NAP1L2 12 (9%) 127 0.689
(1.00) 		0.0733
(1.00) 		0.759
(1.00)
RAC1 11 (8%) 128 0.0429
(1.00) 		0.537
(1.00) 		1
(1.00)
OR51S1 16 (12%) 123 0.415
(1.00) 		0.54
(1.00) 		1
(1.00)
FUT9 16 (12%) 123 0.954
(1.00) 		0.0278
(1.00) 		1
(1.00)
PPP6C 13 (9%) 126 0.0385
(1.00) 		0.767
(1.00) 		0.768
(1.00)
USP29 25 (18%) 114 0.0456
(1.00) 		0.092
(1.00) 		0.367
(1.00)
RPTN 22 (16%) 117 0.545
(1.00) 		0.373
(1.00) 		0.81
(1.00)
TAF1A 8 (6%) 131 0.275
(1.00) 		0.577
(1.00) 		0.465
(1.00)
CDH9 25 (18%) 114 0.333
(1.00) 		0.469
(1.00) 		1
(1.00)
GRXCR1 14 (10%) 125 0.405
(1.00) 		0.0188
(1.00) 		0.573
(1.00)
HIST1H2AA 7 (5%) 132 0.901
(1.00) 		0.99
(1.00) 		0.707
(1.00)
ZNF679 14 (10%) 125 0.952
(1.00) 		0.434
(1.00) 		0.573
(1.00)
C8A 17 (12%) 122 0.00454
(1.00) 		0.00429
(1.00) 		0.0299
(1.00)
RBM11 10 (7%) 129 0.69
(1.00) 		0.288
(1.00) 		0.746
(1.00)
ZNF479 12 (9%) 127 0.36
(1.00) 		0.0896
(1.00) 		0.759
(1.00)
GFRAL 20 (14%) 119 0.473
(1.00) 		0.643
(1.00) 		1
(1.00)
DDX3X 15 (11%) 124 0.613
(1.00) 		0.467
(1.00) 		0.256
(1.00)
OR4M2 16 (12%) 123 0.65
(1.00) 		0.0859
(1.00) 		1
(1.00)
FRG2B 10 (7%) 129 0.503
(1.00) 		0.0228
(1.00) 		0.498
(1.00)
PDE1A 23 (17%) 116 0.309
(1.00) 		0.162
(1.00) 		1
(1.00)
PRB2 21 (15%) 118 0.548
(1.00) 		0.0129
(1.00) 		0.0867
(1.00)
LUZP2 12 (9%) 127 0.651
(1.00) 		0.908
(1.00) 		0.759
(1.00)
NRK 18 (13%) 121 0.34
(1.00) 		0.821
(1.00) 		0.8
(1.00)
PARM1 11 (8%) 128 0.00851
(1.00) 		0.214
(1.00) 		1
(1.00)
SLC38A4 16 (12%) 123 0.786
(1.00) 		0.352
(1.00) 		0.168
(1.00)
PRAMEF11 12 (9%) 127 0.187
(1.00) 		0.151
(1.00) 		0.759
(1.00)
USP17L2 13 (9%) 126 0.64
(1.00) 		0.928
(1.00) 		0.373
(1.00)
PRB1 12 (9%) 127 0.33
(1.00) 		0.554
(1.00) 		0.21
(1.00)
CYLC2 16 (12%) 123 0.616
(1.00) 		0.104
(1.00) 		0.785
(1.00)
DSG3 33 (24%) 106 0.649
(1.00) 		0.134
(1.00) 		0.416
(1.00)
VEGFC 11 (8%) 128 0.943
(1.00) 		0.414
(1.00) 		1
(1.00)
IL32 5 (4%) 134 0.0263
(1.00) 		0.484
(1.00) 		1
(1.00)
LILRB4 21 (15%) 118 0.24
(1.00) 		0.385
(1.00) 		0.81
(1.00)
GLRB 15 (11%) 124 0.478
(1.00) 		0.114
(1.00) 		1
(1.00)
STXBP5L 29 (21%) 110 0.12
(1.00) 		0.538
(1.00) 		0.523
(1.00)
GML 8 (6%) 131 0.932
(1.00) 		0.117
(1.00) 		0.258
(1.00)
TLL1 30 (22%) 109 0.373
(1.00) 		0.235
(1.00) 		0.522
(1.00)
DEFB118 6 (4%) 133 0.141
(1.00) 		0.435
(1.00) 		1
(1.00)
GK2 17 (12%) 122 0.199
(1.00) 		0.968
(1.00) 		1
(1.00)
OR5J2 10 (7%) 129 0.824
(1.00) 		0.942
(1.00) 		0.171
(1.00)
LIN7A 8 (6%) 131 0.412
(1.00) 		0.736
(1.00) 		0.71
(1.00)
MUM1L1 13 (9%) 126 0.357
(1.00) 		0.55
(1.00) 		0.768
(1.00)
MARCH11 7 (5%) 132 0.336
(1.00) 		0.954
(1.00) 		1
(1.00)
PSG4 15 (11%) 124 0.969
(1.00) 		0.462
(1.00) 		0.783
(1.00)
ZIM3 12 (9%) 127 0.0468
(1.00) 		0.968
(1.00) 		0.535
(1.00)
CLEC14A 14 (10%) 125 0.262
(1.00) 		0.905
(1.00) 		0.255
(1.00)
OR5H2 11 (8%) 128 0.421
(1.00) 		0.032
(1.00) 		0.532
(1.00)
TCEB3C 20 (14%) 119 0.508
(1.00) 		0.148
(1.00) 		0.0429
(1.00)
PRB4 16 (12%) 123 0.137
(1.00) 		0.263
(1.00) 		0.412
(1.00)
KLHL4 14 (10%) 125 0.147
(1.00) 		0.666
(1.00) 		0.381
(1.00)
OR52J3 8 (6%) 131 0.149
(1.00) 		0.425
(1.00) 		1
(1.00)
HBD 8 (6%) 131 0.0833
(1.00) 		0.632
(1.00) 		0.465
(1.00)
FAM19A1 7 (5%) 132 0.338
(1.00) 		0.978
(1.00) 		0.707
(1.00)
LRRIQ4 14 (10%) 125 0.449
(1.00) 		0.152
(1.00) 		0.381
(1.00)
SPINK13 4 (3%) 135 0.182
(1.00) 		0.341
(1.00) 		1
(1.00)
SNAP91 17 (12%) 122 0.913
(1.00) 		0.0687
(1.00) 		0.289
(1.00)
LONRF2 10 (7%) 129 0.0751
(1.00) 		0.888
(1.00) 		0.746
(1.00)
CLCC1 7 (5%) 132 0.127
(1.00) 		0.54
(1.00) 		1
(1.00)
KIAA1257 7 (5%) 132 0.0824
(1.00) 		0.0293
(1.00) 		0.423
(1.00)
SIGLEC14 6 (4%) 133 0.872
(1.00) 		0.165
(1.00) 		0.0854
(1.00)
SPANXN2 12 (9%) 127 0.0283
(1.00) 		0.776
(1.00) 		0.535
(1.00)
DEFB112 5 (4%) 134 0.307
(1.00) 		0.282
(1.00) 		1
(1.00)
CD2 14 (10%) 125 0.592
(1.00) 		0.357
(1.00) 		0.771
(1.00)
HTR3B 9 (6%) 130 0.0558
(1.00) 		0.889
(1.00) 		0.154
(1.00)
KIR2DL1 9 (6%) 130 0.412
(1.00) 		0.354
(1.00) 		0.725
(1.00)
OR4N2 17 (12%) 122 0.832
(1.00) 		0.373
(1.00) 		0.0299
(1.00)
ST18 27 (19%) 112 0.791
(1.00) 		0.387
(1.00) 		0.825
(1.00)
TUBB8 7 (5%) 132 0.898
(1.00) 		0.202
(1.00) 		1
(1.00)
C2ORF40 4 (3%) 135 0.732
(1.00) 		0.414
(1.00) 		0.624
(1.00)
PRR23B 9 (6%) 130 0.374
(1.00) 		0.421
(1.00) 		0.725
(1.00)
TFEC 12 (9%) 127 0.199
(1.00) 		0.0329
(1.00) 		0.759
(1.00)
SGCZ 15 (11%) 124 0.0793
(1.00) 		0.868
(1.00) 		1
(1.00)
TRAT1 9 (6%) 130 0.04
(1.00) 		0.681
(1.00) 		0.725
(1.00)
TRIM58 12 (9%) 127 0.415
(1.00) 		0.00268
(1.00) 		1
(1.00)
ANXA10 9 (6%) 130 0.346
(1.00) 		0.248
(1.00) 		0.486
(1.00)
ZNF844 4 (3%) 135 0.426
(1.00) 		0.0198
(1.00) 		0.624
(1.00)
SLC14A1 10 (7%) 129 0.693
(1.00) 		0.129
(1.00) 		0.0136
(1.00)
C9 11 (8%) 128 0.462
(1.00) 		0.897
(1.00) 		0.532
(1.00)
DSG1 21 (15%) 118 0.105
(1.00) 		0.397
(1.00) 		1
(1.00)
CCDC11 13 (9%) 126 0.783
(1.00) 		0.962
(1.00) 		1
(1.00)
MKX 10 (7%) 129 0.476
(1.00) 		0.837
(1.00) 		0.746
(1.00)
OR7D2 13 (9%) 126 0.925
(1.00) 		0.522
(1.00) 		0.373
(1.00)
STARD6 5 (4%) 134 0.848
(1.00) 		0.0446
(1.00) 		1
(1.00)
SPATA8 5 (4%) 134 0.576
(1.00) 		0.0871
(1.00) 		0.356
(1.00)
GRXCR2 11 (8%) 128 0.38
(1.00) 		0.756
(1.00) 		1
(1.00)
OR4A15 14 (10%) 125 0.983
(1.00) 		0.0485
(1.00) 		0.0827
(1.00)
C4ORF22 8 (6%) 131 0.281
(1.00) 		0.614
(1.00) 		0.71
(1.00)
CCDC54 10 (7%) 129 0.468
(1.00) 		0.699
(1.00) 		0.325
(1.00)
CRISP2 8 (6%) 131 0.955
(1.00) 		0.0943
(1.00) 		0.465
(1.00)
MOG 6 (4%) 133 0.866
(1.00) 		0.0659
(1.00) 		0.414
(1.00)
NMS 7 (5%) 132 0.948
(1.00) 		0.169
(1.00) 		0.707
(1.00)
DEFB115 5 (4%) 134 0.935
(1.00) 		0.515
(1.00) 		0.158
(1.00)
UGT2A3 12 (9%) 127 0.999
(1.00) 		0.476
(1.00) 		0.535
(1.00)
ZNF98 12 (9%) 127 0.16
(1.00) 		0.826
(1.00) 		0.759
(1.00)
ADH1C 22 (16%) 117 0.628
(1.00) 		0.242
(1.00) 		0.81
(1.00)
HBG2 6 (4%) 133 0.626
(1.00) 		0.254
(1.00) 		1
(1.00)
HHLA2 9 (6%) 130 0.649
(1.00) 		0.333
(1.00) 		1
(1.00)
IDH1 7 (5%) 132 0.802
(1.00) 		0.0116
(1.00) 		0.261
(1.00)
OR2L3 10 (7%) 129 0.477
(1.00) 		0.703
(1.00) 		0.746
(1.00)
OR4F6 10 (7%) 129 0.166
(1.00) 		0.314
(1.00) 		0.325
(1.00)
B2M 4 (3%) 135 0.685
(1.00) 		0.388
(1.00) 		0.296
(1.00)
ARID2 20 (14%) 119 0.22
(1.00) 		0.151
(1.00) 		0.319
(1.00)
LOC649330 16 (12%) 123 0.288
(1.00) 		0.0226
(1.00) 		0.785
(1.00)
OR5AC2 14 (10%) 125 0.916
(1.00) 		0.764
(1.00) 		0.573
(1.00)
OR5H14 7 (5%) 132 0.357
(1.00) 		0.83
(1.00) 		0.0472
(1.00)
SPAG16 12 (9%) 127 0.251
(1.00) 		0.511
(1.00) 		0.21
(1.00)
SPRY3 8 (6%) 131 0.273
(1.00) 		0.289
(1.00) 		1
(1.00)
STK31 22 (16%) 117 0.825
(1.00) 		0.711
(1.00) 		1
(1.00)
TACR3 13 (9%) 126 0.178
(1.00) 		0.951
(1.00) 		0.768
(1.00)
SERPINB4 18 (13%) 121 0.969
(1.00) 		0.153
(1.00) 		0.0695
(1.00)
TSGA13 6 (4%) 133 0.307
(1.00) 		0.908
(1.00) 		0.414
(1.00)
GIMAP7 11 (8%) 128 0.816
(1.00) 		0.0828
(1.00) 		0.328
(1.00)
SDR16C5 18 (13%) 121 0.603
(1.00) 		0.121
(1.00) 		0.446
(1.00)
SPOCK3 16 (12%) 123 0.739
(1.00) 		0.565
(1.00) 		0.0507
(1.00)
TRHR 15 (11%) 124 0.154
(1.00) 		0.377
(1.00) 		1
(1.00)
CD96 10 (7%) 129 0.92
(1.00) 		0.451
(1.00) 		1
(1.00)
CLEC4E 10 (7%) 129 0.447
(1.00) 		0.245
(1.00) 		0.498
(1.00)
TPTE 36 (26%) 103 0.702
(1.00) 		0.199
(1.00) 		0.691
(1.00)
MCART6 7 (5%) 132 0.763
(1.00) 		0.077
(1.00) 		1
(1.00)
OR2W1 12 (9%) 127 0.726
(1.00) 		0.0799
(1.00) 		0.357
(1.00)
MORF4 10 (7%) 129 0.527
(1.00) 		0.829
(1.00) 		0.746
(1.00)
RGS18 7 (5%) 132 0.981
(1.00) 		0.35
(1.00) 		0.0472
(1.00)
BAGE2 9 (6%) 130 0.806
(1.00) 		0.916
(1.00) 		0.725
(1.00)
KIAA1644 4 (3%) 135 0.388
(1.00) 		0.24
(1.00) 		1
(1.00)
AGXT2 14 (10%) 125 0.205
(1.00) 		0.452
(1.00) 		1
(1.00)
CLDN4 7 (5%) 132 0.914
(1.00) 		0.0532
(1.00) 		0.707
(1.00)
CDH10 21 (15%) 118 0.0274
(1.00) 		0.99
(1.00) 		0.81
(1.00)
VWC2L 11 (8%) 128 0.777
(1.00) 		0.884
(1.00) 		1
(1.00)
ABRA 10 (7%) 129 0.0738
(1.00) 		0.062
(1.00) 		0.325
(1.00)
ARPP21 23 (17%) 116 0.126
(1.00) 		0.0809
(1.00) 		0.154
(1.00)
NR1H4 8 (6%) 131 0.37
(1.00) 		0.287
(1.00) 		0.71
(1.00)
GZMA 8 (6%) 131 0.964
(1.00) 		0.376
(1.00) 		0.71
(1.00)
DGAT2L6 8 (6%) 131 0.504
(1.00) 		0.459
(1.00) 		1
(1.00)
TMCO5A 6 (4%) 133 0.392
(1.00) 		0.275
(1.00) 		0.414
(1.00)
CCNE2 7 (5%) 132 0.136
(1.00) 		0.73
(1.00) 		0.707
(1.00)
CCK 5 (4%) 134 0.128
(1.00) 		0.744
(1.00) 		0.652
(1.00)
ADAMTS20 35 (25%) 104 0.391
(1.00) 		0.13
(1.00) 		0.312
(1.00)
MPP7 17 (12%) 122 0.86
(1.00) 		0.0249
(1.00) 		0.599
(1.00)
FAM155A 9 (6%) 130 0.193
(1.00) 		0.595
(1.00) 		0.288
(1.00)
'MUC7 MUTATION STATUS' versus 'AGE'

P value = 0.000211 (t-test), Q value = 0.094

Table S1.  Gene #11: 'MUC7 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 137 56.5 (16.2)
MUC7 MUTATED 11 72.7 (10.9)
MUC7 WILD-TYPE 126 55.0 (15.8)

Figure S1.  Get High-res Image Gene #11: 'MUC7 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'KRT26 MUTATION STATUS' versus 'Time to Death'

P value = 6.86e-06 (logrank test), Q value = 0.0031

Table S2.  Gene #144: 'KRT26 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 136 67 0.2 - 346.0 (47.5)
KRT26 MUTATED 7 6 2.6 - 44.4 (18.6)
KRT26 WILD-TYPE 129 61 0.2 - 346.0 (48.9)

Figure S2.  Get High-res Image Gene #144: 'KRT26 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

Methods & Data
Input

  • Mutation data file = SKCM-TM.mutsig.cluster.txt

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

  • Number of patients = 139

  • Number of significantly mutated genes = 149

  • Number of selected clinical features = 3

  • 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)
Made with Nozzle