Correlation between copy number variations of arm-level result and selected clinical features
Sarcoma (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1P55KV4
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 selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1P55KV4
Overview
Introduction

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

Summary

Testing the association between copy number variation 78 arm-level events and 3 clinical features across 57 patients, 5 significant findings detected with Q value < 0.25.

- 7Q GAIN MUTATION ANALYSIS cnv correlated to 'AGE'.

- 8P GAIN MUTATION ANALYSIS cnv correlated to 'Time to Death'.

- 8Q GAIN MUTATION ANALYSIS cnv correlated to 'Time to Death'.

- 12P GAIN MUTATION ANALYSIS cnv correlated to 'Time to Death' and 'AGE'.

Results
Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 78 arm-level events and 3 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 5 significant findings detected.

|  | Clinical Features | Time to Death | AGE | GENDER
| nCNV (%) | nWild-Type | logrank test | t-test | Fisher's exact test
12P GAIN MUTATION ANALYSIS | 8 (14%) | 49 | 0.00024 (0.0554) | 6.58e-05 (0.0153) | 1 (1.00)
7Q GAIN MUTATION ANALYSIS | 14 (25%) | 43 | 0.755 (1.00) | 0.000596 (0.137) | 0.23 (1.00)
8P GAIN MUTATION ANALYSIS | 12 (21%) | 45 | 2.87e-05 (0.00671) | 0.13 (1.00) | 0.53 (1.00)
8Q GAIN MUTATION ANALYSIS | 12 (21%) | 45 | 6.12e-05 (0.0143) | 0.252 (1.00) | 1 (1.00)
1P GAIN MUTATION ANALYSIS | 11 (19%) | 46 | 0.0108 (1.00) | 0.0238 (1.00) | 0.747 (1.00)
1Q GAIN MUTATION ANALYSIS | 9 (16%) | 48 | 0.796 (1.00) | 0.0322 (1.00) | 0.73 (1.00)
2P GAIN MUTATION ANALYSIS | 9 (16%) | 48 | 0.273 (1.00) | 0.0451 (1.00) | 0.73 (1.00)
2Q GAIN MUTATION ANALYSIS | 6 (11%) | 51 | 0.709 (1.00) | 0.204 (1.00) | 1 (1.00)
3P GAIN MUTATION ANALYSIS | 6 (11%) | 51 | 0.551 (1.00) | 0.426 (1.00) | 1 (1.00)
3Q GAIN MUTATION ANALYSIS | 7 (12%) | 50 | 0.14 (1.00) | 0.323 (1.00) | 0.706 (1.00)
4P GAIN MUTATION ANALYSIS | 10 (18%) | 47 | 0.823 (1.00) | 0.199 (1.00) | 0.504 (1.00)
4Q GAIN MUTATION ANALYSIS | 8 (14%) | 49 | 0.936 (1.00) | 0.337 (1.00) | 0.706 (1.00)
5P GAIN MUTATION ANALYSIS | 13 (23%) | 44 | 0.642 (1.00) | 0.0377 (1.00) | 1 (1.00)
5Q GAIN MUTATION ANALYSIS | 11 (19%) | 46 | 0.447 (1.00) | 0.161 (1.00) | 0.331 (1.00)
6P GAIN MUTATION ANALYSIS | 10 (18%) | 47 | 0.945 (1.00) | 0.00694 (1.00) | 1 (1.00)
6Q GAIN MUTATION ANALYSIS | 12 (21%) | 45 | 0.706 (1.00) | 0.0363 (1.00) | 0.747 (1.00)
7P GAIN MUTATION ANALYSIS | 16 (28%) | 41 | 0.646 (1.00) | 0.00132 (0.302) | 0.0819 (1.00)
9P GAIN MUTATION ANALYSIS | 9 (16%) | 48 | 0.621 (1.00) | 0.0144 (1.00) | 1 (1.00)
9Q GAIN MUTATION ANALYSIS | 14 (25%) | 43 | 0.225 (1.00) | 0.0452 (1.00) | 0.76 (1.00)
10P GAIN MUTATION ANALYSIS | 5 (9%) | 52 | 0.00429 (0.965) | 0.598 (1.00) | 1 (1.00)
11P GAIN MUTATION ANALYSIS | 3 (5%) | 54 | 0.43 (1.00) | 0.0642 (1.00) | 0.112 (1.00)
11Q GAIN MUTATION ANALYSIS | 3 (5%) | 54 | 0.454 (1.00) | 0.476 (1.00) | 0.112 (1.00)
12Q GAIN MUTATION ANALYSIS | 4 (7%) | 53 | 0.176 (1.00) | 0.0115 (1.00) | 1 (1.00)
14Q GAIN MUTATION ANALYSIS | 9 (16%) | 48 | 0.207 (1.00) | 0.636 (1.00) | 1 (1.00)
15Q GAIN MUTATION ANALYSIS | 12 (21%) | 45 | 0.357 (1.00) | 0.0262 (1.00) | 1 (1.00)
16P GAIN MUTATION ANALYSIS | 11 (19%) | 46 | 0.0463 (1.00) | 0.43 (1.00) | 0.747 (1.00)
16Q GAIN MUTATION ANALYSIS | 4 (7%) | 53 | 0.803 (1.00) | 0.826 (1.00) | 1 (1.00)
17P GAIN MUTATION ANALYSIS | 12 (21%) | 45 | 0.0334 (1.00) | 0.0258 (1.00) | 1 (1.00)
17Q GAIN MUTATION ANALYSIS | 10 (18%) | 47 | 0.413 (1.00) | 0.204 (1.00) | 0.179 (1.00)
18P GAIN MUTATION ANALYSIS | 10 (18%) | 47 | 0.31 (1.00) | 0.056 (1.00) | 0.179 (1.00)
18Q GAIN MUTATION ANALYSIS | 10 (18%) | 47 | 0.957 (1.00) | 0.106 (1.00) | 0.0411 (1.00)
19P GAIN MUTATION ANALYSIS | 19 (33%) | 38 | 0.0286 (1.00) | 0.00885 (1.00) | 0.576 (1.00)
19Q GAIN MUTATION ANALYSIS | 13 (23%) | 44 | 0.517 (1.00) | 0.0259 (1.00) | 1 (1.00)
20P GAIN MUTATION ANALYSIS | 17 (30%) | 40 | 0.0847 (1.00) | 0.0396 (1.00) | 0.777 (1.00)
20Q GAIN MUTATION ANALYSIS | 20 (35%) | 37 | 0.221 (1.00) | 0.174 (1.00) | 1 (1.00)
21Q GAIN MUTATION ANALYSIS | 11 (19%) | 46 | 0.0197 (1.00) | 0.118 (1.00) | 0.504 (1.00)
22Q GAIN MUTATION ANALYSIS | 9 (16%) | 48 | 0.325 (1.00) | 0.105 (1.00) | 0.0787 (1.00)
XQ GAIN MUTATION ANALYSIS | 7 (12%) | 50 | 0.704 (1.00) | 0.677 (1.00) | 1 (1.00)
1P LOSS MUTATION ANALYSIS | 10 (18%) | 47 | 0.112 (1.00) | 0.247 (1.00) | 0.0411 (1.00)
1Q LOSS MUTATION ANALYSIS | 10 (18%) | 47 | 0.604 (1.00) | 0.353 (1.00) | 0.504 (1.00)
2P LOSS MUTATION ANALYSIS | 10 (18%) | 47 | 0.902 (1.00) | 0.0102 (1.00) | 1 (1.00)
2Q LOSS MUTATION ANALYSIS | 12 (21%) | 45 | 0.209 (1.00) | 0.00209 (0.475) | 1 (1.00)
3P LOSS MUTATION ANALYSIS | 12 (21%) | 45 | 0.326 (1.00) | 0.0697 (1.00) | 1 (1.00)
3Q LOSS MUTATION ANALYSIS | 12 (21%) | 45 | 0.855 (1.00) | 0.0803 (1.00) | 1 (1.00)
4P LOSS MUTATION ANALYSIS | 11 (19%) | 46 | 0.522 (1.00) | 0.433 (1.00) | 0.331 (1.00)
4Q LOSS MUTATION ANALYSIS | 14 (25%) | 43 | 0.506 (1.00) | 0.627 (1.00) | 0.07 (1.00)
5P LOSS MUTATION ANALYSIS | 7 (12%) | 50 | 0.0773 (1.00) | 0.358 (1.00) | 1 (1.00)
5Q LOSS MUTATION ANALYSIS | 10 (18%) | 47 | 0.219 (1.00) | 0.598 (1.00) | 1 (1.00)
6P LOSS MUTATION ANALYSIS | 10 (18%) | 47 | 0.212 (1.00) | 0.796 (1.00) | 0.504 (1.00)
6Q LOSS MUTATION ANALYSIS | 5 (9%) | 52 | 0.186 (1.00) | 0.961 (1.00) | 0.194 (1.00)
7P LOSS MUTATION ANALYSIS | 4 (7%) | 53 | 0.234 (1.00) | 0.42 (1.00) | 1 (1.00)
7Q LOSS MUTATION ANALYSIS | 4 (7%) | 53 | 0.494 (1.00) | 0.0585 (1.00) | 0.611 (1.00)
8P LOSS MUTATION ANALYSIS | 13 (23%) | 44 | 0.482 (1.00) | 0.0459 (1.00) | 0.358 (1.00)
8Q LOSS MUTATION ANALYSIS | 11 (19%) | 46 | 0.482 (1.00) | 0.0137 (1.00) | 0.331 (1.00)
9P LOSS MUTATION ANALYSIS | 17 (30%) | 40 | 0.576 (1.00) | 0.00861 (1.00) | 0.395 (1.00)
9Q LOSS MUTATION ANALYSIS | 11 (19%) | 46 | 0.455 (1.00) | 0.0278 (1.00) | 0.331 (1.00)
10P LOSS MUTATION ANALYSIS | 23 (40%) | 34 | 0.712 (1.00) | 0.013 (1.00) | 0.00297 (0.675)
10Q LOSS MUTATION ANALYSIS | 25 (44%) | 32 | 0.186 (1.00) | 0.23 (1.00) | 0.0033 (0.746)
11P LOSS MUTATION ANALYSIS | 25 (44%) | 32 | 0.332 (1.00) | 0.0112 (1.00) | 0.596 (1.00)
11Q LOSS MUTATION ANALYSIS | 19 (33%) | 38 | 0.186 (1.00) | 0.0091 (1.00) | 0.576 (1.00)
12P LOSS MUTATION ANALYSIS | 12 (21%) | 45 | 0.539 (1.00) | 0.391 (1.00) | 0.747 (1.00)
12Q LOSS MUTATION ANALYSIS | 14 (25%) | 43 | 0.362 (1.00) | 0.745 (1.00) | 1 (1.00)
13Q LOSS MUTATION ANALYSIS | 25 (44%) | 32 | 0.458 (1.00) | 0.0351 (1.00) | 0.186 (1.00)
14Q LOSS MUTATION ANALYSIS | 21 (37%) | 36 | 0.192 (1.00) | 0.974 (1.00) | 0.787 (1.00)
15Q LOSS MUTATION ANALYSIS | 11 (19%) | 46 | 0.16 (1.00) | 0.0651 (1.00) | 0.331 (1.00)
16P LOSS MUTATION ANALYSIS | 15 (26%) | 42 | 0.491 (1.00) | 0.208 (1.00) | 0.379 (1.00)
16Q LOSS MUTATION ANALYSIS | 27 (47%) | 30 | 0.103 (1.00) | 0.161 (1.00) | 0.189 (1.00)
17P LOSS MUTATION ANALYSIS | 11 (19%) | 46 | 0.357 (1.00) | 0.464 (1.00) | 0.747 (1.00)
17Q LOSS MUTATION ANALYSIS | 7 (12%) | 50 | 0.495 (1.00) | 0.217 (1.00) | 0.706 (1.00)
18P LOSS MUTATION ANALYSIS | 14 (25%) | 43 | 0.728 (1.00) | 0.697 (1.00) | 0.07 (1.00)
18Q LOSS MUTATION ANALYSIS | 15 (26%) | 42 | 0.319 (1.00) | 0.0162 (1.00) | 0.379 (1.00)
19P LOSS MUTATION ANALYSIS | 4 (7%) | 53 | 0.297 (1.00) | 0.165 (1.00) | 0.352 (1.00)
19Q LOSS MUTATION ANALYSIS | 10 (18%) | 47 | 0.882 (1.00) | 0.138 (1.00) | 0.73 (1.00)
20P LOSS MUTATION ANALYSIS | 7 (12%) | 50 | 0.518 (1.00) | 0.26 (1.00) | 1 (1.00)
20Q LOSS MUTATION ANALYSIS | 5 (9%) | 52 | 0.827 (1.00) | 0.207 (1.00) | 1 (1.00)
21Q LOSS MUTATION ANALYSIS | 13 (23%) | 44 | 0.147 (1.00) | 0.207 (1.00) | 0.76 (1.00)
22Q LOSS MUTATION ANALYSIS | 21 (37%) | 36 | 0.839 (1.00) | 0.567 (1.00) | 0.787 (1.00)
XQ LOSS MUTATION ANALYSIS | 19 (33%) | 38 | 0.82 (1.00) | 0.956 (1.00) | 0.783 (1.00)

'7Q GAIN MUTATION STATUS' versus 'AGE'

P value = 0.000596 (t-test), Q value = 0.14

Table S1. Gene #14: '7Q GAIN MUTATION STATUS' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 57 | 63.4 (11.5)
7Q GAIN MUTATED | 14 | 70.5 (6.7)
7Q GAIN WILD-TYPE | 43 | 61.0 (11.9)

Figure S1. Get High-res Image Gene #14: '7Q GAIN MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'8P GAIN MUTATION STATUS' versus 'Time to Death'

P value = 2.87e-05 (logrank test), Q value = 0.0067

Table S2. Gene #15: '8P GAIN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 57 | 18 | 0.1 - 143.4 (18.5)
8P GAIN MUTATED | 12 | 7 | 0.1 - 74.7 (5.2)
8P GAIN WILD-TYPE | 45 | 11 | 0.1 - 143.4 (24.5)

Figure S2. Get High-res Image Gene #15: '8P GAIN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'8Q GAIN MUTATION STATUS' versus 'Time to Death'

P value = 6.12e-05 (logrank test), Q value = 0.014

Table S3. Gene #16: '8Q GAIN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 57 | 18 | 0.1 - 143.4 (18.5)
8Q GAIN MUTATED | 12 | 7 | 0.1 - 74.7 (5.2)
8Q GAIN WILD-TYPE | 45 | 11 | 0.1 - 143.4 (23.1)

Figure S3. Get High-res Image Gene #16: '8Q GAIN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'12P GAIN MUTATION STATUS' versus 'Time to Death'

P value = 0.00024 (logrank test), Q value = 0.055

Table S4. Gene #22: '12P GAIN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 57 | 18 | 0.1 - 143.4 (18.5)
12P GAIN MUTATED | 8 | 6 | 0.1 - 27.2 (10.9)
12P GAIN WILD-TYPE | 49 | 12 | 0.1 - 143.4 (21.4)

Figure S4. Get High-res Image Gene #22: '12P GAIN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'12P GAIN MUTATION STATUS' versus 'AGE'

P value = 6.58e-05 (t-test), Q value = 0.015

Table S5. Gene #22: '12P GAIN MUTATION STATUS' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 57 | 63.4 (11.5)
12P GAIN MUTATED | 8 | 74.9 (5.7)
12P GAIN WILD-TYPE | 49 | 61.5 (11.2)

Figure S5. Get High-res Image Gene #22: '12P GAIN MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

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

- Clinical data file = SARC-TP.clin.merged.picked.txt

- Number of patients = 57

- Number of significantly arm-level cnvs = 78

- Number of selected clinical features = 3

- Exclude regions 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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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