Correlation between copy number variation genes (focal events) and molecular subtypes
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between copy number variation genes (focal events) and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C19C6VT1
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and molecular subtypes.

Summary

Testing the association between copy number variation 40 focal events and 8 molecular subtypes across 171 patients, 10 significant findings detected with P value < 0.05 and Q value < 0.25.

  • 4p cnv correlated to 'CN_CNMF'.

  • 4q cnv correlated to 'CN_CNMF'.

  • 5p cnv correlated to 'CN_CNMF'.

  • 5q cnv correlated to 'CN_CNMF'.

  • 7q cnv correlated to 'MIRSEQ_CNMF' and 'MIRSEQ_MATURE_CNMF'.

  • 16q cnv correlated to 'MIRSEQ_CHIERARCHICAL'.

  • 17p cnv correlated to 'CN_CNMF'.

  • 19p cnv correlated to 'CN_CNMF'.

  • 19q cnv correlated to 'CN_CNMF'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 40 focal events and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 10 significant findings detected.

Clinical
Features
CN
CNMF
METHLYATION
CNMF
MRNASEQ
CNMF
MRNASEQ
CHIERARCHICAL
MIRSEQ
CNMF
MIRSEQ
CHIERARCHICAL
MIRSEQ
MATURE
CNMF
MIRSEQ
MATURE
CHIERARCHICAL
nCNV (%) nWild-Type Fisher's exact test Chi-square test Chi-square test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
7q 43 (25%) 128 0.0123
(1.00)
0.684
(1.00)
0.416
(1.00)
0.821
(1.00)
0.000572
(0.178)
0.399
(1.00)
0.000326
(0.102)
0.533
(1.00)
4p 73 (43%) 98 1.47e-05
(0.00463)
0.231
(1.00)
0.704
(1.00)
0.00218
(0.671)
0.34
(1.00)
0.335
(1.00)
0.329
(1.00)
0.183
(1.00)
4q 52 (30%) 119 1.86e-05
(0.00587)
0.501
(1.00)
0.361
(1.00)
0.141
(1.00)
0.698
(1.00)
0.0608
(1.00)
0.377
(1.00)
0.53
(1.00)
5p 69 (40%) 102 7.6e-09
(2.43e-06)
0.0584
(1.00)
0.82
(1.00)
0.223
(1.00)
0.189
(1.00)
0.438
(1.00)
0.31
(1.00)
0.598
(1.00)
5q 57 (33%) 114 1.78e-08
(5.68e-06)
0.0201
(1.00)
0.946
(1.00)
1
(1.00)
0.191
(1.00)
0.178
(1.00)
0.219
(1.00)
0.826
(1.00)
16q 44 (26%) 127 0.289
(1.00)
0.00863
(1.00)
0.0813
(1.00)
0.0188
(1.00)
0.00975
(1.00)
0.000267
(0.0835)
0.0433
(1.00)
0.00898
(1.00)
17p 60 (35%) 111 6.59e-07
(0.00021)
0.674
(1.00)
0.532
(1.00)
0.742
(1.00)
0.61
(1.00)
0.62
(1.00)
0.259
(1.00)
0.208
(1.00)
19p 56 (33%) 115 3.94e-05
(0.0124)
0.178
(1.00)
0.251
(1.00)
0.273
(1.00)
0.0148
(1.00)
0.109
(1.00)
0.0266
(1.00)
0.119
(1.00)
19q 55 (32%) 116 4.45e-06
(0.00141)
0.175
(1.00)
0.693
(1.00)
0.686
(1.00)
0.0015
(0.463)
0.272
(1.00)
0.0143
(1.00)
0.148
(1.00)
1p 61 (36%) 110 0.382
(1.00)
0.0952
(1.00)
0.108
(1.00)
0.167
(1.00)
0.799
(1.00)
0.693
(1.00)
0.858
(1.00)
0.532
(1.00)
1q 87 (51%) 84 0.0341
(1.00)
0.049
(1.00)
0.268
(1.00)
0.381
(1.00)
1
(1.00)
0.425
(1.00)
0.724
(1.00)
0.874
(1.00)
2p 45 (26%) 126 0.00203
(0.624)
0.0573
(1.00)
0.384
(1.00)
0.318
(1.00)
0.118
(1.00)
0.0283
(1.00)
0.637
(1.00)
0.294
(1.00)
2q 40 (23%) 131 0.026
(1.00)
0.123
(1.00)
0.787
(1.00)
0.852
(1.00)
0.323
(1.00)
0.27
(1.00)
0.711
(1.00)
0.729
(1.00)
3p 81 (47%) 90 0.351
(1.00)
0.346
(1.00)
0.815
(1.00)
0.0506
(1.00)
0.107
(1.00)
0.434
(1.00)
0.00359
(1.00)
0.0296
(1.00)
3q 108 (63%) 63 0.0032
(0.972)
0.0127
(1.00)
0.0329
(1.00)
0.00445
(1.00)
0.363
(1.00)
0.00487
(1.00)
0.185
(1.00)
0.00695
(1.00)
6p 55 (32%) 116 0.275
(1.00)
0.25
(1.00)
0.315
(1.00)
0.671
(1.00)
0.932
(1.00)
0.338
(1.00)
0.738
(1.00)
0.458
(1.00)
6q 59 (35%) 112 0.149
(1.00)
0.23
(1.00)
0.346
(1.00)
0.892
(1.00)
0.795
(1.00)
0.451
(1.00)
0.476
(1.00)
0.807
(1.00)
7p 34 (20%) 137 0.0848
(1.00)
0.6
(1.00)
0.434
(1.00)
0.712
(1.00)
0.00538
(1.00)
0.709
(1.00)
0.00281
(0.861)
0.618
(1.00)
8p 71 (42%) 100 0.0193
(1.00)
0.082
(1.00)
0.501
(1.00)
0.742
(1.00)
0.889
(1.00)
0.681
(1.00)
1
(1.00)
0.497
(1.00)
8q 59 (35%) 112 0.0386
(1.00)
0.308
(1.00)
0.565
(1.00)
0.244
(1.00)
0.304
(1.00)
0.0975
(1.00)
0.535
(1.00)
0.286
(1.00)
9p 58 (34%) 113 0.0459
(1.00)
0.953
(1.00)
0.557
(1.00)
0.704
(1.00)
0.97
(1.00)
0.453
(1.00)
0.77
(1.00)
1
(1.00)
9q 53 (31%) 118 0.0555
(1.00)
0.977
(1.00)
0.305
(1.00)
0.335
(1.00)
0.897
(1.00)
0.435
(1.00)
0.706
(1.00)
0.422
(1.00)
10p 50 (29%) 121 0.026
(1.00)
0.642
(1.00)
0.39
(1.00)
0.412
(1.00)
0.545
(1.00)
0.117
(1.00)
0.706
(1.00)
0.531
(1.00)
10q 51 (30%) 120 0.0362
(1.00)
0.465
(1.00)
0.142
(1.00)
0.221
(1.00)
0.401
(1.00)
0.0497
(1.00)
0.329
(1.00)
0.355
(1.00)
11p 58 (34%) 113 0.0271
(1.00)
0.361
(1.00)
0.378
(1.00)
0.421
(1.00)
0.73
(1.00)
0.231
(1.00)
0.356
(1.00)
0.675
(1.00)
11q 71 (42%) 100 0.0038
(1.00)
0.609
(1.00)
0.852
(1.00)
0.752
(1.00)
0.57
(1.00)
0.939
(1.00)
0.582
(1.00)
0.279
(1.00)
12p 51 (30%) 120 0.00778
(1.00)
0.601
(1.00)
0.834
(1.00)
0.51
(1.00)
0.449
(1.00)
0.69
(1.00)
0.462
(1.00)
0.746
(1.00)
12q 34 (20%) 137 0.0453
(1.00)
0.405
(1.00)
0.0888
(1.00)
0.636
(1.00)
0.129
(1.00)
0.607
(1.00)
0.354
(1.00)
0.67
(1.00)
13q 58 (34%) 113 0.168
(1.00)
0.296
(1.00)
0.39
(1.00)
0.122
(1.00)
0.228
(1.00)
0.556
(1.00)
0.0626
(1.00)
0.329
(1.00)
14q 44 (26%) 127 0.0198
(1.00)
0.458
(1.00)
0.175
(1.00)
0.0878
(1.00)
0.101
(1.00)
0.015
(1.00)
0.069
(1.00)
0.0786
(1.00)
15q 52 (30%) 119 0.077
(1.00)
0.576
(1.00)
0.979
(1.00)
0.219
(1.00)
0.228
(1.00)
0.164
(1.00)
0.297
(1.00)
0.859
(1.00)
16p 42 (25%) 129 0.0916
(1.00)
0.0762
(1.00)
0.302
(1.00)
0.181
(1.00)
0.0077
(1.00)
0.0143
(1.00)
0.0416
(1.00)
0.0862
(1.00)
17q 42 (25%) 129 0.00525
(1.00)
0.627
(1.00)
0.375
(1.00)
0.509
(1.00)
0.453
(1.00)
0.726
(1.00)
0.736
(1.00)
0.611
(1.00)
18p 53 (31%) 118 0.0555
(1.00)
0.966
(1.00)
0.34
(1.00)
1
(1.00)
0.698
(1.00)
0.673
(1.00)
0.715
(1.00)
1
(1.00)
18q 55 (32%) 116 0.0429
(1.00)
0.239
(1.00)
0.00496
(1.00)
0.151
(1.00)
0.512
(1.00)
0.0536
(1.00)
0.476
(1.00)
0.212
(1.00)
20p 67 (39%) 104 0.00135
(0.418)
0.0598
(1.00)
0.204
(1.00)
0.0476
(1.00)
0.572
(1.00)
0.0731
(1.00)
0.428
(1.00)
0.249
(1.00)
20q 67 (39%) 104 0.0175
(1.00)
0.0582
(1.00)
0.404
(1.00)
0.212
(1.00)
0.809
(1.00)
0.182
(1.00)
0.645
(1.00)
0.563
(1.00)
21q 51 (30%) 120 0.0443
(1.00)
0.823
(1.00)
0.128
(1.00)
0.39
(1.00)
0.906
(1.00)
1
(1.00)
0.77
(1.00)
0.887
(1.00)
22q 59 (35%) 112 0.00721
(1.00)
0.248
(1.00)
0.273
(1.00)
0.73
(1.00)
0.0241
(1.00)
0.128
(1.00)
0.0487
(1.00)
0.215
(1.00)
xq 59 (35%) 112 0.533
(1.00)
0.0192
(1.00)
0.207
(1.00)
0.0242
(1.00)
0.00444
(1.00)
0.118
(1.00)
0.00298
(0.908)
0.00974
(1.00)
'4p' versus 'CN_CNMF'

P value = 1.47e-05 (Fisher's exact test), Q value = 0.0046

Table S1.  Gene #7: '4p' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 58 36 77
4P MUTATED 27 26 20
4P WILD-TYPE 31 10 57

Figure S1.  Get High-res Image Gene #7: '4p' versus Molecular Subtype #1: 'CN_CNMF'

'4q' versus 'CN_CNMF'

P value = 1.86e-05 (Fisher's exact test), Q value = 0.0059

Table S2.  Gene #8: '4q' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 58 36 77
4Q MUTATED 17 22 13
4Q WILD-TYPE 41 14 64

Figure S2.  Get High-res Image Gene #8: '4q' versus Molecular Subtype #1: 'CN_CNMF'

'5p' versus 'CN_CNMF'

P value = 7.6e-09 (Fisher's exact test), Q value = 2.4e-06

Table S3.  Gene #9: '5p' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 58 36 77
5P MUTATED 24 29 16
5P WILD-TYPE 34 7 61

Figure S3.  Get High-res Image Gene #9: '5p' versus Molecular Subtype #1: 'CN_CNMF'

'5q' versus 'CN_CNMF'

P value = 1.78e-08 (Fisher's exact test), Q value = 5.7e-06

Table S4.  Gene #10: '5q' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 58 36 77
5Q MUTATED 16 27 14
5Q WILD-TYPE 42 9 63

Figure S4.  Get High-res Image Gene #10: '5q' versus Molecular Subtype #1: 'CN_CNMF'

'7q' versus 'MIRSEQ_CNMF'

P value = 0.000572 (Fisher's exact test), Q value = 0.18

Table S5.  Gene #14: '7q' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 57 44 54
7Q MUTATED 22 3 16
7Q WILD-TYPE 35 41 38

Figure S5.  Get High-res Image Gene #14: '7q' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

'7q' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.000326 (Fisher's exact test), Q value = 0.1

Table S6.  Gene #14: '7q' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 57 47 51
7Q MUTATED 21 3 17
7Q WILD-TYPE 36 44 34

Figure S6.  Get High-res Image Gene #14: '7q' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

'16q' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.000267 (Fisher's exact test), Q value = 0.084

Table S7.  Gene #29: '16q' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 48 20 37 50
16Q MUTATED 5 7 19 11
16Q WILD-TYPE 43 13 18 39

Figure S7.  Get High-res Image Gene #29: '16q' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

'17p' versus 'CN_CNMF'

P value = 6.59e-07 (Fisher's exact test), Q value = 0.00021

Table S8.  Gene #30: '17p' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 58 36 77
17P MUTATED 25 23 12
17P WILD-TYPE 33 13 65

Figure S8.  Get High-res Image Gene #30: '17p' versus Molecular Subtype #1: 'CN_CNMF'

'19p' versus 'CN_CNMF'

P value = 3.94e-05 (Fisher's exact test), Q value = 0.012

Table S9.  Gene #34: '19p' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 58 36 77
19P MUTATED 17 23 16
19P WILD-TYPE 41 13 61

Figure S9.  Get High-res Image Gene #34: '19p' versus Molecular Subtype #1: 'CN_CNMF'

'19q' versus 'CN_CNMF'

P value = 4.45e-06 (Fisher's exact test), Q value = 0.0014

Table S10.  Gene #35: '19q' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 58 36 77
19Q MUTATED 16 24 15
19Q WILD-TYPE 42 12 62

Figure S10.  Get High-res Image Gene #35: '19q' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data
Input
  • Copy number data file = transformed.cor.cli.txt

  • Molecular subtype file = CESC-TP.transferedmergedcluster.txt

  • Number of patients = 171

  • Number of significantly focal cnvs = 40

  • Number of molecular subtypes = 8

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

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

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.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.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References
[1] 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)
[2] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[3] 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)