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

Sarcoma (Primary solid tumor)

16 April 2014 | analyses__2014_04_16

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 selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1C53JJ4

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 58 focal events and 3 clinical features across 103 patients, 4 significant findings detected with Q value < 0.25.

amp_7q31.1 cnv correlated to 'AGE'.
del_2p25.3 cnv correlated to 'GENDER'.
del_11q24.3 cnv correlated to 'AGE'.
del_18q23 cnv correlated to 'AGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 58 focal events and 3 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 4 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test
amp 7q31 1	29 (28%)	74	0.375 (1.00)	0.000268 (0.0467)	0.827 (1.00)
del 2p25 3	35 (34%)	68	0.762 (1.00)	0.32 (1.00)	0.000371 (0.0643)
del 11q24 3	42 (41%)	61	0.179 (1.00)	0.00144 (0.247)	0.694 (1.00)
del 18q23	33 (32%)	70	0.391 (1.00)	0.000482 (0.0829)	0.294 (1.00)
amp 1p32 1	31 (30%)	72	0.158 (1.00)	0.24 (1.00)	0.669 (1.00)
amp 1q24 3	40 (39%)	63	0.806 (1.00)	0.51 (1.00)	0.691 (1.00)
amp 3p11 2	23 (22%)	80	0.269 (1.00)	0.00748 (1.00)	1 (1.00)
amp 5p15 33	45 (44%)	58	0.0404 (1.00)	0.00458 (0.761)	0.427 (1.00)
amp 6p21 1	22 (21%)	81	0.192 (1.00)	0.00878 (1.00)	0.336 (1.00)
amp 6q24 3	30 (29%)	73	0.645 (1.00)	0.0381 (1.00)	0.518 (1.00)
amp 8q21 12	36 (35%)	67	0.0124 (1.00)	0.0674 (1.00)	1 (1.00)
amp 11q22 2	16 (16%)	87	0.919 (1.00)	0.56 (1.00)	1 (1.00)
amp 12p13 32	19 (18%)	84	0.0659 (1.00)	0.114 (1.00)	0.8 (1.00)
amp 12q15	42 (41%)	61	0.7 (1.00)	0.176 (1.00)	0.0176 (1.00)
amp 13q34	16 (16%)	87	0.358 (1.00)	0.452 (1.00)	0.0144 (1.00)
amp 17p11 2	34 (33%)	69	0.225 (1.00)	0.144 (1.00)	0.0957 (1.00)
amp 17q24 3	25 (24%)	78	0.0276 (1.00)	0.0358 (1.00)	0.0105 (1.00)
amp 19p13 2	34 (33%)	69	0.997 (1.00)	0.294 (1.00)	0.53 (1.00)
amp 19q12	34 (33%)	69	0.14 (1.00)	0.0287 (1.00)	0.678 (1.00)
amp 20q13 33	39 (38%)	64	0.35 (1.00)	0.0121 (1.00)	0.416 (1.00)
amp 21q21 1	26 (25%)	77	0.495 (1.00)	0.0231 (1.00)	0.502 (1.00)
amp xp21 1	31 (30%)	72	0.576 (1.00)	0.741 (1.00)	0.0534 (1.00)
amp xq21 2	14 (14%)	89	0.0802 (1.00)	0.0712 (1.00)	1 (1.00)
del 1p36 32	33 (32%)	70	0.0258 (1.00)	0.0706 (1.00)	0.0583 (1.00)
del 1p32 3	18 (17%)	85	0.0505 (1.00)	0.763 (1.00)	0.0206 (1.00)
del 1q44	27 (26%)	76	0.646 (1.00)	0.422 (1.00)	0.503 (1.00)
del 2q37 3	36 (35%)	67	0.0411 (1.00)	0.311 (1.00)	0.22 (1.00)
del 2q37 3	37 (36%)	66	0.362 (1.00)	0.106 (1.00)	0.155 (1.00)
del 3p21 31	19 (18%)	84	0.217 (1.00)	0.0678 (1.00)	0.323 (1.00)
del 3q29	24 (23%)	79	0.324 (1.00)	0.224 (1.00)	1 (1.00)
del 4q35 1	36 (35%)	67	0.122 (1.00)	0.107 (1.00)	0.414 (1.00)
del 6p25 1	36 (35%)	67	0.863 (1.00)	0.486 (1.00)	0.22 (1.00)
del 6q14 1	23 (22%)	80	0.364 (1.00)	0.257 (1.00)	0.813 (1.00)
del 7q36 3	24 (23%)	79	0.145 (1.00)	0.782 (1.00)	0.819 (1.00)
del 8p23 3	28 (27%)	75	0.945 (1.00)	0.437 (1.00)	0.272 (1.00)
del 9p24 3	39 (38%)	64	0.878 (1.00)	0.00225 (0.378)	0.549 (1.00)
del 9p21 3	45 (44%)	58	0.913 (1.00)	0.0235 (1.00)	0.427 (1.00)
del 9q34 3	21 (20%)	82	0.186 (1.00)	0.732 (1.00)	0.463 (1.00)
del 10p15 3	50 (49%)	53	0.222 (1.00)	0.191 (1.00)	0.0762 (1.00)
del 10q23 31	57 (55%)	46	0.322 (1.00)	0.699 (1.00)	0.00157 (0.266)
del 11p15 5	41 (40%)	62	0.358 (1.00)	0.00547 (0.903)	0.554 (1.00)
del 12p13 1	29 (28%)	74	0.915 (1.00)	0.348 (1.00)	0.191 (1.00)
del 12q12	21 (20%)	82	0.613 (1.00)	0.786 (1.00)	1 (1.00)
del 13q14 2	69 (67%)	34	0.216 (1.00)	0.0175 (1.00)	0.0589 (1.00)
del 14q24 1	35 (34%)	68	0.236 (1.00)	0.619 (1.00)	0.537 (1.00)
del 15q11 2	19 (18%)	84	0.334 (1.00)	0.0664 (1.00)	0.0117 (1.00)
del 16q12 1	57 (55%)	46	0.28 (1.00)	0.327 (1.00)	0.0181 (1.00)
del 17p13 1	42 (41%)	61	0.699 (1.00)	0.621 (1.00)	0.0702 (1.00)
del 17q11 2	24 (23%)	79	0.558 (1.00)	0.0556 (1.00)	1 (1.00)
del 17q25 3	25 (24%)	78	0.4 (1.00)	0.116 (1.00)	0.651 (1.00)
del 19p13 3	28 (27%)	75	0.267 (1.00)	0.302 (1.00)	0.00166 (0.28)
del 19q13 43	37 (36%)	66	0.622 (1.00)	0.612 (1.00)	0.0671 (1.00)
del 21q11 2	19 (18%)	84	0.807 (1.00)	0.211 (1.00)	0.622 (1.00)
del 21q22 3	30 (29%)	73	0.601 (1.00)	0.00242 (0.405)	0.666 (1.00)
del 22q13 31	34 (33%)	69	0.467 (1.00)	0.408 (1.00)	0.0957 (1.00)
del xp22 32	31 (30%)	72	0.256 (1.00)	0.0413 (1.00)	0.285 (1.00)
del xq21 1	52 (50%)	51	0.277 (1.00)	0.217 (1.00)	0.0104 (1.00)
del xq27 1	51 (50%)	52	0.856 (1.00)	0.93 (1.00)	0.018 (1.00)

'amp_7q31.1' versus 'AGE'

P value = 0.000268 (t-test), Q value = 0.047

Table S1. Gene #7: 'amp_7q31.1' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	103	62.4 (12.9)
AMP PEAK 7(7Q31.1) MUTATED	29	69.7 (11.8)
AMP PEAK 7(7Q31.1) WILD-TYPE	74	59.5 (12.3)

Figure S1. Get High-res Image Gene #7: 'amp_7q31.1' versus Clinical Feature #2: 'AGE'

'del_2p25.3' versus 'GENDER'

P value = 0.000371 (Fisher's exact test), Q value = 0.064

Table S2. Gene #24: 'del_2p25.3' versus Clinical Feature #3: 'GENDER'

nPatients	FEMALE	MALE
ALL	54	49
DEL PEAK 4(2P25.3) MUTATED	27	8
DEL PEAK 4(2P25.3) WILD-TYPE	27	41

Figure S2. Get High-res Image Gene #24: 'del_2p25.3' versus Clinical Feature #3: 'GENDER'

'del_11q24.3' versus 'AGE'

P value = 0.00144 (t-test), Q value = 0.25

Table S3. Gene #40: 'del_11q24.3' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	103	62.4 (12.9)
DEL PEAK 20(11Q24.3) MUTATED	42	67.2 (12.0)
DEL PEAK 20(11Q24.3) WILD-TYPE	61	59.1 (12.6)

Figure S3. Get High-res Image Gene #40: 'del_11q24.3' versus Clinical Feature #2: 'AGE'

'del_18q23' versus 'AGE'

P value = 0.000482 (t-test), Q value = 0.083

Table S4. Gene #50: 'del_18q23' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	103	62.4 (12.9)
DEL PEAK 30(18Q23) MUTATED	33	68.6 (11.3)
DEL PEAK 30(18Q23) WILD-TYPE	70	59.5 (12.7)

Figure S4. Get High-res Image Gene #50: 'del_18q23' versus Clinical Feature #2: 'AGE'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = SARC-TP.merged_data.txt
Number of patients = 103
Number of significantly focal cnvs = 58
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.

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] 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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