Correlation between copy number variation genes (focal events) and selected clinical features
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and selected clinical features.

Summary

Testing the association between copy number variation 65 focal events and 7 clinical features across 22 patients, no significant finding detected with Q value < 0.25.

  • No focal cnvs related to clinical features.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 65 focal events and 7 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, no significant finding detected.

Clinical
Features 		Time
to
Death 		AGE NEOPLASM
DISEASESTAGE 		PATHOLOGY
T
STAGE 		PATHOLOGY
N
STAGE 		GENDER NUMBERPACKYEARSSMOKED
nCNV (%) nWild-Type logrank test t-test Chi-square test Fisher's exact test Fisher's exact test Fisher's exact test t-test
amp 1p34 2 7 (32%) 15 0.374
(1.00) 		0.0718
(1.00) 		0.785
(1.00) 		0.0622
(1.00) 		0.424
(1.00) 		0.227
(1.00) 		0.67
(1.00)
amp 1q21 3 15 (68%) 7 0.593
(1.00) 		0.274
(1.00) 		0.773
(1.00) 		0.58
(1.00) 		0.586
(1.00) 		1
(1.00) 		0.623
(1.00)
amp 2q14 2 6 (27%) 16 0.582
(1.00) 		0.509
(1.00) 		0.452
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.429
(1.00)
amp 3q26 2 19 (86%) 3 0.356
(1.00) 		0.662
(1.00) 		0.282
(1.00) 		0.15
(1.00) 		0.26
(1.00) 		0.371
(1.00)
amp 5p15 33 9 (41%) 13 0.474
(1.00) 		0.393
(1.00) 		0.212
(1.00) 		1
(1.00) 		0.146
(1.00) 		0.544
(1.00) 		0.432
(1.00)
amp 6p21 1 8 (36%) 14 0.975
(1.00) 		0.815
(1.00) 		0.782
(1.00) 		0.228
(1.00) 		1
(1.00) 		0.0364
(1.00) 		0.534
(1.00)
amp 6q12 7 (32%) 15 0.181
(1.00) 		0.809
(1.00) 		0.877
(1.00) 		0.231
(1.00) 		0.842
(1.00) 		1
(1.00) 		0.704
(1.00)
amp 7p11 2 16 (73%) 6 0.721
(1.00) 		0.0608
(1.00) 		0.556
(1.00) 		0.587
(1.00) 		0.685
(1.00) 		0.532
(1.00) 		0.535
(1.00)
amp 7q21 2 15 (68%) 7 0.318
(1.00) 		0.13
(1.00) 		0.482
(1.00) 		1
(1.00) 		1
(1.00) 		0.523
(1.00) 		0.211
(1.00)
amp 8p11 21 13 (59%) 9 0.584
(1.00) 		0.054
(1.00) 		0.141
(1.00) 		0.0789
(1.00) 		0.858
(1.00) 		1
(1.00) 		0.0604
(1.00)
amp 8q24 21 19 (86%) 3 0.187
(1.00) 		0.833
(1.00) 		0.648
(1.00) 		0.75
(1.00) 		1
(1.00) 		1
(1.00)
amp 9p13 3 4 (18%) 18 0.734
(1.00) 		0.286
(1.00) 		0.688
(1.00) 		0.141
(1.00) 		0.631
(1.00) 		1
(1.00)
amp 11p13 5 (23%) 17 0.161
(1.00) 		0.722
(1.00) 		0.908
(1.00) 		0.108
(1.00) 		1
(1.00) 		1
(1.00) 		0.613
(1.00)
amp 11q13 3 11 (50%) 11 0.0805
(1.00) 		0.791
(1.00) 		0.808
(1.00) 		1
(1.00) 		0.483
(1.00) 		1
(1.00) 		0.54
(1.00)
amp 12p13 33 9 (41%) 13 0.907
(1.00) 		0.383
(1.00) 		0.24
(1.00) 		0.271
(1.00) 		0.626
(1.00) 		1
(1.00) 		0.405
(1.00)
amp 12p12 1 9 (41%) 13 0.108
(1.00) 		1
(1.00) 		0.738
(1.00) 		0.271
(1.00) 		0.332
(1.00) 		1
(1.00) 		0.0812
(1.00)
amp 14q22 1 7 (32%) 15 0.131
(1.00) 		0.228
(1.00) 		0.785
(1.00) 		0.231
(1.00) 		0.296
(1.00) 		1
(1.00) 		0.998
(1.00)
amp 17q12 11 (50%) 11 0.184
(1.00) 		0.231
(1.00) 		0.543
(1.00) 		0.725
(1.00) 		0.247
(1.00) 		1
(1.00) 		0.212
(1.00)
amp 17q24 3 12 (55%) 10 0.948
(1.00) 		0.97
(1.00) 		0.272
(1.00) 		0.453
(1.00) 		0.733
(1.00) 		0.0779
(1.00) 		0.213
(1.00)
amp 18p11 32 7 (32%) 15 0.105
(1.00) 		0.968
(1.00) 		0.15
(1.00) 		0.702
(1.00) 		0.704
(1.00) 		0.227
(1.00) 		0.635
(1.00)
amp 18q11 2 7 (32%) 15 0.893
(1.00) 		0.887
(1.00) 		0.0548
(1.00) 		0.152
(1.00) 		0.158
(1.00) 		1
(1.00) 		0.109
(1.00)
amp 19p13 2 3 (14%) 19 0.212
(1.00) 		0.568
(1.00) 		0.75
(1.00) 		0.558
(1.00) 		1
(1.00)
amp 19q12 8 (36%) 14 0.746
(1.00) 		0.00196
(0.874) 		0.413
(1.00) 		0.312
(1.00) 		0.131
(1.00) 		1
(1.00) 		0.181
(1.00)
amp xp11 4 4 (18%) 18 0.0134
(1.00) 		0.746
(1.00) 		0.807
(1.00) 		0.0511
(1.00) 		0.803
(1.00) 		0.47
(1.00) 		0.881
(1.00)
del 1p36 13 10 (45%) 12 0.948
(1.00) 		0.97
(1.00) 		0.307
(1.00) 		1
(1.00) 		0.236
(1.00) 		1
(1.00) 		0.784
(1.00)
del 1p13 2 10 (45%) 12 0.746
(1.00) 		0.593
(1.00) 		0.561
(1.00) 		0.168
(1.00) 		0.864
(1.00) 		1
(1.00) 		0.543
(1.00)
del 1q44 3 (14%) 19 0.412
(1.00) 		0.0283
(1.00) 		0.012
(1.00) 		0.257
(1.00) 		0.0026
(1.00) 		1
(1.00)
del 2q22 1 9 (41%) 13 0.904
(1.00) 		0.793
(1.00) 		0.304
(1.00) 		0.232
(1.00) 		0.332
(1.00) 		1
(1.00) 		0.188
(1.00)
del 2q33 3 5 (23%) 17 0.881
(1.00) 		0.745
(1.00) 		0.318
(1.00) 		0.649
(1.00) 		0.663
(1.00) 		1
(1.00) 		0.336
(1.00)
del 3p14 3 15 (68%) 7 0.111
(1.00) 		0.0582
(1.00) 		0.324
(1.00) 		0.702
(1.00) 		0.586
(1.00) 		1
(1.00) 		0.211
(1.00)
del 3p14 2 16 (73%) 6 0.172
(1.00) 		0.175
(1.00) 		0.475
(1.00) 		0.587
(1.00) 		0.82
(1.00) 		1
(1.00) 		0.0862
(1.00)
del 3q26 31 3 (14%) 19 0.352
(1.00) 		0.888
(1.00) 		0.799
(1.00) 		0.15
(1.00) 		0.26
(1.00) 		1
(1.00) 		0.325
(1.00)
del 4p15 2 14 (64%) 8 0.132
(1.00) 		0.331
(1.00) 		0.367
(1.00) 		0.228
(1.00) 		0.068
(1.00) 		1
(1.00) 		0.156
(1.00)
del 4q21 23 10 (45%) 12 0.357
(1.00) 		0.13
(1.00) 		0.222
(1.00) 		0.743
(1.00) 		0.624
(1.00) 		0.571
(1.00) 		0.0459
(1.00)
del 4q22 1 12 (55%) 10 0.161
(1.00) 		0.0188
(1.00) 		0.222
(1.00) 		0.453
(1.00) 		0.17
(1.00) 		1
(1.00) 		0.217
(1.00)
del 5q11 2 13 (59%) 9 0.434
(1.00) 		0.39
(1.00) 		0.619
(1.00) 		0.614
(1.00) 		0.858
(1.00) 		0.24
(1.00) 		0.875
(1.00)
del 5q12 3 13 (59%) 9 0.434
(1.00) 		0.39
(1.00) 		0.619
(1.00) 		0.614
(1.00) 		0.858
(1.00) 		0.24
(1.00) 		0.875
(1.00)
del 6p25 3 9 (41%) 13 0.137
(1.00) 		0.819
(1.00) 		0.884
(1.00) 		1
(1.00) 		0.525
(1.00) 		1
(1.00) 		0.0708
(1.00)
del 6q16 1 4 (18%) 18 0.715
(1.00) 		0.852
(1.00) 		0.602
(1.00) 		0.0148
(1.00) 		0.803
(1.00) 		1
(1.00)
del 7q31 1 9 (41%) 13 0.974
(1.00) 		0.292
(1.00) 		0.468
(1.00) 		0.139
(1.00) 		0.44
(1.00) 		1
(1.00) 		0.0966
(1.00)
del 7q36 2 9 (41%) 13 0.986
(1.00) 		0.79
(1.00) 		0.183
(1.00) 		0.0372
(1.00) 		0.146
(1.00) 		1
(1.00) 		0.447
(1.00)
del 8p23 2 12 (55%) 10 0.72
(1.00) 		0.685
(1.00) 		0.561
(1.00) 		0.236
(1.00) 		0.624
(1.00) 		0.0779
(1.00) 		0.641
(1.00)
del 9p21 3 19 (86%) 3 0.0838
(1.00) 		0.00235
(1.00) 		0.506
(1.00) 		0.75
(1.00) 		0.766
(1.00) 		1
(1.00)
del 10p11 21 6 (27%) 16 0.25
(1.00) 		0.783
(1.00) 		0.556
(1.00) 		0.587
(1.00) 		0.82
(1.00) 		0.532
(1.00) 		0.298
(1.00)
del 10q23 31 9 (41%) 13 0.764
(1.00) 		0.191
(1.00) 		0.738
(1.00) 		0.521
(1.00) 		1
(1.00) 		0.544
(1.00) 		0.953
(1.00)
del 11p15 4 6 (27%) 16 0.5
(1.00) 		0.666
(1.00) 		0.122
(1.00) 		0.105
(1.00) 		0.82
(1.00) 		0.532
(1.00) 		0.706
(1.00)
del 11q24 3 9 (41%) 13 0.313
(1.00) 		0.97
(1.00) 		0.153
(1.00) 		0.373
(1.00) 		0.626
(1.00) 		1
(1.00) 		0.216
(1.00)
del 12q23 1 6 (27%) 16 0.922
(1.00) 		0.943
(1.00) 		0.156
(1.00) 		0.309
(1.00) 		0.583
(1.00) 		0.169
(1.00) 		0.891
(1.00)
del 13q12 11 12 (55%) 10 0.974
(1.00) 		0.881
(1.00) 		0.191
(1.00) 		0.321
(1.00) 		0.00265
(1.00) 		0.571
(1.00) 		0.107
(1.00)
del 13q14 2 13 (59%) 9 0.313
(1.00) 		0.91
(1.00) 		0.124
(1.00) 		0.167
(1.00) 		0.0989
(1.00) 		0.544
(1.00) 		0.617
(1.00)
del 15q11 2 5 (23%) 17 0.137
(1.00) 		0.494
(1.00) 		0.0177
(1.00) 		0.158
(1.00) 		0.00706
(1.00) 		1
(1.00) 		0.543
(1.00)
del 16q23 1 10 (45%) 12 0.117
(1.00) 		0.0897
(1.00) 		0.467
(1.00) 		0.453
(1.00) 		0.343
(1.00) 		0.571
(1.00) 		0.558
(1.00)
del 17p11 2 9 (41%) 13 0.893
(1.00) 		0.62
(1.00) 		0.153
(1.00) 		0.861
(1.00) 		0.332
(1.00) 		1
(1.00) 		0.878
(1.00)
del 17q25 3 4 (18%) 18 0.571
(1.00) 		0.51
(1.00) 		0.211
(1.00) 		1
(1.00) 		0.347
(1.00) 		1
(1.00) 		0.573
(1.00)
del 18q12 2 12 (55%) 10 0.631
(1.00) 		0.113
(1.00) 		0.827
(1.00) 		0.2
(1.00) 		0.733
(1.00) 		0.571
(1.00) 		0.287
(1.00)
del 18q21 2 12 (55%) 10 0.975
(1.00) 		0.198
(1.00) 		0.827
(1.00) 		0.2
(1.00) 		0.733
(1.00) 		0.0779
(1.00) 		0.67
(1.00)
del 19p13 3 14 (64%) 8 0.908
(1.00) 		1
(1.00) 		0.843
(1.00) 		0.856
(1.00) 		0.194
(1.00) 		1
(1.00) 		0.792
(1.00)
del 19q13 31 6 (27%) 16 0.356
(1.00) 		0.425
(1.00) 		0.826
(1.00) 		1
(1.00) 		0.403
(1.00) 		0.169
(1.00) 		0.921
(1.00)
del 20p12 1 3 (14%) 19 0.412
(1.00) 		0.381
(1.00) 		0.17
(1.00) 		0.4
(1.00) 		0.109
(1.00) 		1
(1.00)
del 21q21 1 15 (68%) 7 0.369
(1.00) 		0.532
(1.00) 		0.383
(1.00) 		0.423
(1.00) 		0.704
(1.00) 		0.523
(1.00) 		0.197
(1.00)
del 21q22 12 13 (59%) 9 0.843
(1.00) 		0.461
(1.00) 		0.619
(1.00) 		1
(1.00) 		0.525
(1.00) 		0.24
(1.00) 		0.0403
(1.00)
del 22q11 1 11 (50%) 11 0.788
(1.00) 		0.164
(1.00) 		0.808
(1.00) 		1
(1.00) 		0.85
(1.00) 		1
(1.00) 		0.665
(1.00)
del xp21 1 12 (55%) 10 0.962
(1.00) 		0.461
(1.00) 		0.307
(1.00) 		0.321
(1.00) 		0.733
(1.00) 		0.571
(1.00) 		0.719
(1.00)
del xp11 3 13 (59%) 9 0.974
(1.00) 		0.27
(1.00) 		0.529
(1.00) 		0.167
(1.00) 		0.332
(1.00) 		0.544
(1.00) 		0.21
(1.00)
del xq21 33 4 (18%) 18 0.5
(1.00) 		0.637
(1.00) 		0.00756
(1.00) 		0.257
(1.00) 		0.0195
(1.00) 		0.47
(1.00)
Methods & Data
Input

  • Copy number data file = transformed.cor.cli.txt

  • Clinical data file = ESCA-TP.merged_data.txt

  • Number of patients = 22

  • Number of significantly focal cnvs = 65

  • Number of selected clinical features = 7

  • 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

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

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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[4] 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)
[5] 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