Correlation between copy number variations of arm-level result and molecular subtypes
Cervical Squamous Cell Carcinoma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1RB72S4
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between copy number variations of arm-level result and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1RB72S4
Overview
Introduction

This pipeline computes the correlation between significant arm-level copy number variations (cnvs) and subtypes.

Summary

Testing the association between copy number variation 73 arm-level results and 6 molecular subtypes across 114 patients, 3 significant findings detected with Q value < 0.25.

  • 4q loss cnv correlated to 'CN_CNMF'.

  • 7q loss cnv correlated to 'MRNASEQ_CHIERARCHICAL'.

  • 21q loss 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 73 arm-level results and 6 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.

Molecular
subtypes 		CN
CNMF 		METHLYATION
CNMF 		MRNASEQ
CNMF 		MRNASEQ
CHIERARCHICAL 		MIRSEQ
CNMF 		MIRSEQ
CHIERARCHICAL
nCNV (%) nWild-Type Fisher's exact test Chi-square test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
4q loss 23 (20%) 91 3e-07
(0.00013) 		0.239
(1.00) 		0.0661
(1.00) 		0.164
(1.00) 		0.474
(1.00) 		0.501
(1.00)
7q loss 13 (11%) 101 0.324
(1.00) 		0.175
(1.00) 		0.00803
(1.00) 		0.000251
(0.108) 		0.0136
(1.00) 		0.0909
(1.00)
21q loss 13 (11%) 101 0.00011
(0.0477) 		0.0152
(1.00) 		0.731
(1.00) 		0.598
(1.00) 		1
(1.00) 		0.868
(1.00)
1p gain 30 (26%) 84 0.925
(1.00) 		0.51
(1.00) 		0.335
(1.00) 		0.104
(1.00) 		0.668
(1.00) 		0.655
(1.00)
1q gain 41 (36%) 73 0.182
(1.00) 		0.771
(1.00) 		0.403
(1.00) 		0.117
(1.00) 		0.185
(1.00) 		0.634
(1.00)
2p gain 16 (14%) 98 0.108
(1.00) 		0.0917
(1.00) 		0.0371
(1.00) 		0.23
(1.00) 		0.0943
(1.00) 		0.0418
(1.00)
2q gain 4 (4%) 110 0.0917
(1.00) 		0.374
(1.00) 		0.16
(1.00) 		0.418
(1.00) 		1
(1.00) 		1
(1.00)
3p gain 20 (18%) 94 0.312
(1.00) 		0.0889
(1.00) 		0.378
(1.00) 		0.378
(1.00) 		0.748
(1.00) 		0.667
(1.00)
3q gain 57 (50%) 57 0.00857
(1.00) 		0.0156
(1.00) 		0.00217
(0.923) 		0.000921
(0.397) 		0.633
(1.00) 		0.0309
(1.00)
4q gain 3 (3%) 111 0.313
(1.00) 		0.32
(1.00) 		0.458
(1.00) 		0.278
(1.00) 		0.203
(1.00) 		0.343
(1.00)
5p gain 37 (32%) 77 0.00806
(1.00) 		0.934
(1.00) 		0.706
(1.00) 		0.921
(1.00) 		0.0819
(1.00) 		0.293
(1.00)
5q gain 13 (11%) 101 1
(1.00) 		0.532
(1.00) 		1
(1.00) 		0.711
(1.00) 		0.325
(1.00) 		0.451
(1.00)
6p gain 14 (12%) 100 0.221
(1.00) 		0.019
(1.00) 		0.00456
(1.00) 		0.0609
(1.00) 		0.0237
(1.00) 		0.0619
(1.00)
6q gain 8 (7%) 106 0.803
(1.00) 		0.259
(1.00) 		0.161
(1.00) 		0.0414
(1.00) 		0.309
(1.00) 		0.0708
(1.00)
7p gain 6 (5%) 108 0.564
(1.00) 		0.0623
(1.00) 		0.139
(1.00) 		0.0763
(1.00) 		0.366
(1.00) 		0.281
(1.00)
7q gain 10 (9%) 104 0.175
(1.00) 		0.527
(1.00) 		0.223
(1.00) 		0.266
(1.00) 		0.71
(1.00) 		0.918
(1.00)
8p gain 11 (10%) 103 0.656
(1.00) 		0.467
(1.00) 		0.144
(1.00) 		0.0303
(1.00) 		0.725
(1.00) 		0.919
(1.00)
8q gain 21 (18%) 93 0.249
(1.00) 		0.515
(1.00) 		0.0684
(1.00) 		0.103
(1.00) 		0.32
(1.00) 		0.319
(1.00)
9p gain 10 (9%) 104 0.836
(1.00) 		0.8
(1.00) 		0.741
(1.00) 		0.259
(1.00) 		0.844
(1.00) 		0.0911
(1.00)
9q gain 10 (9%) 104 0.356
(1.00) 		0.248
(1.00) 		0.318
(1.00) 		0.0613
(1.00) 		0.772
(1.00) 		0.272
(1.00)
10p gain 7 (6%) 107 1
(1.00) 		0.946
(1.00) 		0.651
(1.00) 		0.542
(1.00) 		0.296
(1.00) 		1
(1.00)
10q gain 4 (4%) 110 0.812
(1.00) 		0.522
(1.00) 		1
(1.00) 		1
(1.00) 		0.387
(1.00) 		0.693
(1.00)
12p gain 14 (12%) 100 0.26
(1.00) 		0.471
(1.00) 		0.219
(1.00) 		0.166
(1.00) 		0.163
(1.00) 		0.334
(1.00)
12q gain 10 (9%) 104 0.391
(1.00) 		0.505
(1.00) 		0.895
(1.00) 		0.618
(1.00) 		0.545
(1.00) 		0.838
(1.00)
13q gain 4 (4%) 110 0.256
(1.00) 		0.256
(1.00) 		0.464
(1.00) 		0.693
(1.00)
14q gain 9 (8%) 105 0.737
(1.00) 		0.393
(1.00) 		0.258
(1.00) 		0.0974
(1.00) 		0.289
(1.00) 		0.739
(1.00)
15q gain 13 (11%) 101 0.193
(1.00) 		0.398
(1.00) 		0.477
(1.00) 		0.744
(1.00) 		0.933
(1.00) 		0.931
(1.00)
16p gain 13 (11%) 101 0.193
(1.00) 		0.332
(1.00) 		0.646
(1.00) 		0.891
(1.00) 		0.21
(1.00) 		0.267
(1.00)
16q gain 9 (8%) 105 0.236
(1.00) 		0.45
(1.00) 		1
(1.00) 		1
(1.00) 		0.208
(1.00) 		0.287
(1.00)
17p gain 4 (4%) 110 0.555
(1.00) 		0.217
(1.00) 		1
(1.00) 		1
(1.00) 		0.159
(1.00) 		0.029
(1.00)
17q gain 11 (10%) 103 0.77
(1.00) 		0.275
(1.00) 		0.161
(1.00) 		0.0414
(1.00) 		0.348
(1.00) 		0.099
(1.00)
18p gain 11 (10%) 103 0.77
(1.00) 		0.0219
(1.00) 		0.52
(1.00) 		0.548
(1.00) 		0.23
(1.00) 		0.19
(1.00)
18q gain 6 (5%) 108 1
(1.00) 		0.00157
(0.673) 		0.616
(1.00) 		0.783
(1.00) 		0.316
(1.00) 		0.136
(1.00)
19p gain 8 (7%) 106 0.361
(1.00) 		0.555
(1.00) 		0.619
(1.00) 		0.576
(1.00) 		0.146
(1.00) 		0.894
(1.00)
19q gain 20 (18%) 94 0.0384
(1.00) 		0.077
(1.00) 		0.463
(1.00) 		0.262
(1.00) 		0.0068
(1.00) 		0.094
(1.00)
20p gain 30 (26%) 84 0.00308
(1.00) 		0.398
(1.00) 		1
(1.00) 		0.632
(1.00) 		0.413
(1.00) 		0.562
(1.00)
20q gain 35 (31%) 79 0.0595
(1.00) 		0.482
(1.00) 		0.918
(1.00) 		0.144
(1.00) 		0.548
(1.00) 		0.432
(1.00)
21q gain 14 (12%) 100 0.87
(1.00) 		0.4
(1.00) 		0.0714
(1.00) 		0.18
(1.00) 		0.163
(1.00) 		0.504
(1.00)
22q gain 7 (6%) 107 0.0485
(1.00) 		0.0034
(1.00) 		0.237
(1.00) 		0.0763
(1.00) 		0.0298
(1.00) 		0.884
(1.00)
Xq gain 6 (5%) 108 0.0422
(1.00) 		0.569
(1.00) 		0.268
(1.00) 		0.705
(1.00) 		0.161
(1.00) 		0.761
(1.00)
1q loss 3 (3%) 111 0.21
(1.00) 		0.183
(1.00) 		0.103
(1.00) 		0.0595
(1.00) 		0.647
(1.00) 		1
(1.00)
2p loss 3 (3%) 111 0.792
(1.00) 		0.268
(1.00) 		0.773
(1.00) 		0.792
(1.00)
2q loss 5 (4%) 109 0.299
(1.00) 		0.0193
(1.00) 		0.124
(1.00) 		0.172
(1.00) 		1
(1.00) 		1
(1.00)
3p loss 26 (23%) 88 0.594
(1.00) 		0.00335
(1.00) 		0.688
(1.00) 		0.0852
(1.00) 		0.0127
(1.00) 		0.00406
(1.00)
4p loss 37 (32%) 77 0.00304
(1.00) 		0.308
(1.00) 		0.795
(1.00) 		0.96
(1.00) 		0.11
(1.00) 		0.763
(1.00)
5p loss 3 (3%) 111 0.792
(1.00) 		0.238
(1.00) 		0.787
(1.00) 		0.278
(1.00) 		1
(1.00) 		0.616
(1.00)
5q loss 17 (15%) 97 0.0193
(1.00) 		0.359
(1.00) 		0.888
(1.00) 		0.352
(1.00) 		0.116
(1.00) 		0.0474
(1.00)
6p loss 13 (11%) 101 0.275
(1.00) 		0.532
(1.00) 		0.223
(1.00) 		0.266
(1.00) 		0.71
(1.00) 		0.805
(1.00)
6q loss 23 (20%) 91 0.912
(1.00) 		0.18
(1.00) 		0.504
(1.00) 		0.503
(1.00) 		0.434
(1.00) 		0.66
(1.00)
7p loss 6 (5%) 108 0.261
(1.00) 		0.514
(1.00) 		0.0124
(1.00) 		0.058
(1.00) 		0.0958
(1.00) 		0.483
(1.00)
8p loss 27 (24%) 87 0.41
(1.00) 		0.175
(1.00) 		0.219
(1.00) 		0.819
(1.00) 		0.925
(1.00) 		0.921
(1.00)
8q loss 7 (6%) 107 0.413
(1.00) 		0.231
(1.00) 		0.0398
(1.00) 		0.121
(1.00) 		0.339
(1.00) 		0.00487
(1.00)
9p loss 9 (8%) 105 0.143
(1.00) 		0.639
(1.00) 		0.318
(1.00) 		0.482
(1.00) 		0.289
(1.00) 		0.287
(1.00)
9q loss 10 (9%) 104 0.356
(1.00) 		0.0416
(1.00) 		0.35
(1.00) 		0.153
(1.00) 		0.844
(1.00) 		0.0534
(1.00)
10p loss 20 (18%) 94 0.135
(1.00) 		0.36
(1.00) 		0.398
(1.00) 		0.691
(1.00) 		0.583
(1.00) 		0.397
(1.00)
10q loss 22 (19%) 92 0.195
(1.00) 		0.66
(1.00) 		0.802
(1.00) 		0.463
(1.00) 		0.279
(1.00) 		1
(1.00)
11p loss 23 (20%) 91 0.0718
(1.00) 		0.46
(1.00) 		0.368
(1.00) 		0.9
(1.00) 		0.312
(1.00) 		0.66
(1.00)
11q loss 25 (22%) 89 0.00105
(0.452) 		0.0151
(1.00) 		0.802
(1.00) 		0.889
(1.00) 		0.313
(1.00) 		0.457
(1.00)
12p loss 15 (13%) 99 0.185
(1.00) 		0.142
(1.00) 		0.127
(1.00) 		1
(1.00) 		0.326
(1.00) 		0.355
(1.00)
12q loss 4 (4%) 110 0.0218
(1.00) 		0.188
(1.00) 		0.285
(1.00) 		0.655
(1.00) 		1
(1.00) 		0.809
(1.00)
13q loss 21 (18%) 93 0.605
(1.00) 		0.121
(1.00) 		0.836
(1.00) 		0.562
(1.00) 		0.911
(1.00) 		0.191
(1.00)
14q loss 7 (6%) 107 0.413
(1.00) 		0.231
(1.00) 		0.00515
(1.00) 		0.0416
(1.00) 		0.0373
(1.00) 		0.00487
(1.00)
15q loss 8 (7%) 106 0.144
(1.00) 		0.444
(1.00) 		0.28
(1.00) 		1
(1.00) 		0.905
(1.00) 		0.807
(1.00)
16p loss 7 (6%) 107 0.886
(1.00) 		0.173
(1.00) 		0.595
(1.00) 		0.602
(1.00) 		0.794
(1.00) 		0.169
(1.00)
16q loss 13 (11%) 101 1
(1.00) 		0.0376
(1.00) 		0.0603
(1.00) 		0.0414
(1.00) 		0.614
(1.00) 		0.00792
(1.00)
17p loss 26 (23%) 88 0.0115
(1.00) 		0.604
(1.00) 		0.293
(1.00) 		0.86
(1.00) 		0.0282
(1.00) 		0.111
(1.00)
17q loss 5 (4%) 109 1
(1.00) 		0.37
(1.00) 		0.219
(1.00) 		1
(1.00) 		0.37
(1.00) 		0.519
(1.00)
18p loss 16 (14%) 98 0.316
(1.00) 		0.112
(1.00) 		0.0244
(1.00) 		0.0827
(1.00) 		0.367
(1.00) 		0.0642
(1.00)
18q loss 22 (19%) 92 0.392
(1.00) 		0.00179
(0.763) 		0.00162
(0.691) 		0.00262
(1.00) 		0.103
(1.00) 		0.00237
(1.00)
19p loss 11 (10%) 103 0.461
(1.00) 		0.0944
(1.00) 		0.141
(1.00) 		0.356
(1.00) 		0.195
(1.00) 		0.00108
(0.465)
19q loss 6 (5%) 108 0.406
(1.00) 		0.569
(1.00) 		0.482
(1.00) 		1
(1.00) 		0.596
(1.00) 		0.0298
(1.00)
20p loss 5 (4%) 109 0.299
(1.00) 		0.789
(1.00) 		0.616
(1.00) 		0.783
(1.00) 		1
(1.00) 		0.595
(1.00)
22q loss 12 (11%) 102 0.668
(1.00) 		0.0597
(1.00) 		0.526
(1.00) 		0.0879
(1.00) 		1
(1.00) 		0.926
(1.00)
'4q loss mutation analysis' versus 'CN_CNMF'

P value = 3e-07 (Fisher's exact test), Q value = 0.00013

Table S1.  Gene #43: '4q loss mutation analysis' versus Clinical Feature #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 35 25 54
4Q LOSS MUTATED 5 15 3
4Q LOSS WILD-TYPE 30 10 51

Figure S1.  Get High-res Image Gene #43: '4q loss mutation analysis' versus Clinical Feature #1: 'CN_CNMF'

'7q loss mutation analysis' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.000251 (Fisher's exact test), Q value = 0.11

Table S2.  Gene #49: '7q loss mutation analysis' versus Clinical Feature #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 24 49
7Q LOSS MUTATED 7 5 1
7Q LOSS WILD-TYPE 13 19 48

Figure S2.  Get High-res Image Gene #49: '7q loss mutation analysis' versus Clinical Feature #4: 'MRNASEQ_CHIERARCHICAL'

'21q loss mutation analysis' versus 'CN_CNMF'

P value = 0.00011 (Fisher's exact test), Q value = 0.048

Table S3.  Gene #72: '21q loss mutation analysis' versus Clinical Feature #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 35 25 54
21Q LOSS MUTATED 6 7 0
21Q LOSS WILD-TYPE 29 18 54

Figure S3.  Get High-res Image Gene #72: '21q loss mutation analysis' versus Clinical Feature #1: 'CN_CNMF'

Methods & Data
Input

  • Mutation data file = broad_values_by_arm.mutsig.cluster.txt

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

  • Number of patients = 114

  • Number of significantly arm-level cnvs = 73

  • Number of molecular subtypes = 6

  • Exclude genes that fewer than K tumors have mutations, 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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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)
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