Correlation between copy number variations of arm-level result and selected clinical features

Mesothelioma (Primary solid tumor)

17 October 2014 | analyses__2014_10_17

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 variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C16H4G9F

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 55 arm-level events and 7 clinical features across 39 patients, 2 significant findings detected with Q value < 0.25.

11q loss cnv correlated to 'Time to Death'.
17q loss cnv correlated to 'Time to Death'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 55 arm-level events and 7 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.


		Clinical Features	Time to Death	AGE	NEOPLASM DISEASESTAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	GENDER
	nCNV (%)	nWild-Type	logrank test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
11q loss	4 (10%)	35	4.41e-05 (0.0168)	0.186 (1.00)	0.0304 (1.00)	0.0567 (1.00)	1 (1.00)	0.618 (1.00)	0.556 (1.00)
17q loss	3 (8%)	36	0.000236 (0.0896)	0.279 (1.00)	0.187 (1.00)	0.28 (1.00)		0.51 (1.00)	1 (1.00)
1p gain	5 (13%)	34	0.236 (1.00)	0.866 (1.00)	0.315 (1.00)	1 (1.00)	0.613 (1.00)	0.672 (1.00)	1 (1.00)
1q gain	12 (31%)	27	0.351 (1.00)	0.703 (1.00)	0.282 (1.00)	0.434 (1.00)	0.483 (1.00)	0.181 (1.00)	1 (1.00)
3p gain	10 (26%)	29	0.715 (1.00)	0.872 (1.00)	0.459 (1.00)	0.344 (1.00)	0.73 (1.00)	1 (1.00)	0.696 (1.00)
3q gain	12 (31%)	27	0.543 (1.00)	0.988 (1.00)	0.369 (1.00)	0.278 (1.00)	0.745 (1.00)	0.538 (1.00)	0.693 (1.00)
5p gain	9 (23%)	30	0.647 (1.00)	0.0916 (1.00)	0.617 (1.00)	0.336 (1.00)	0.847 (1.00)	0.774 (1.00)	0.669 (1.00)
5q gain	5 (13%)	34	0.865 (1.00)	0.199 (1.00)	0.313 (1.00)	0.379 (1.00)	1 (1.00)	0.376 (1.00)	0.587 (1.00)
7p gain	10 (26%)	29	0.258 (1.00)	0.43 (1.00)	0.695 (1.00)	0.346 (1.00)	0.0953 (1.00)	1 (1.00)	1 (1.00)
7q gain	9 (23%)	30	0.417 (1.00)	0.151 (1.00)	1 (1.00)	0.12 (1.00)	0.0581 (1.00)	1 (1.00)	1 (1.00)
8p gain	7 (18%)	32	0.111 (1.00)	0.322 (1.00)	0.737 (1.00)	0.0351 (1.00)	0.157 (1.00)	1 (1.00)	0.653 (1.00)
8q gain	8 (21%)	31	0.0302 (1.00)	0.577 (1.00)	0.359 (1.00)	0.0528 (1.00)	0.156 (1.00)	0.742 (1.00)	0.653 (1.00)
11q gain	3 (8%)	36	0.257 (1.00)	0.0162 (1.00)	0.795 (1.00)	0.387 (1.00)	0.677 (1.00)	0.102 (1.00)	1 (1.00)
12p gain	11 (28%)	28	0.985 (1.00)	0.888 (1.00)	0.36 (1.00)	0.409 (1.00)	0.0947 (1.00)	1 (1.00)	0.228 (1.00)
12q gain	11 (28%)	28	0.985 (1.00)	0.888 (1.00)	0.357 (1.00)	0.409 (1.00)	0.0944 (1.00)	1 (1.00)	0.228 (1.00)
15q gain	4 (10%)	35	0.107 (1.00)	0.0461 (1.00)	0.375 (1.00)	0.654 (1.00)	0.551 (1.00)	1 (1.00)	1 (1.00)
16p gain	7 (18%)	32	0.679 (1.00)	0.133 (1.00)	0.497 (1.00)	1 (1.00)	0.228 (1.00)	1 (1.00)	1 (1.00)
16q gain	8 (21%)	31	0.377 (1.00)	0.0647 (1.00)	0.494 (1.00)	0.875 (1.00)	0.367 (1.00)	1 (1.00)	0.399 (1.00)
17p gain	3 (8%)	36	0.519 (1.00)	0.0813 (1.00)	0.0631 (1.00)	0.0379 (1.00)	0.428 (1.00)	1 (1.00)	0.556 (1.00)
17q gain	10 (26%)	29	0.682 (1.00)	0.747 (1.00)	0.693 (1.00)	1 (1.00)	0.0101 (1.00)	1 (1.00)	0.402 (1.00)
18p gain	3 (8%)	36	0.0881 (1.00)	0.937 (1.00)	0.233 (1.00)	0.778 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
18q gain	3 (8%)	36	0.0881 (1.00)	0.937 (1.00)	0.236 (1.00)	0.776 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
19p gain	5 (13%)	34	0.236 (1.00)	0.983 (1.00)	0.35 (1.00)	1 (1.00)	0.615 (1.00)	0.671 (1.00)	1 (1.00)
19q gain	4 (10%)	35	0.125 (1.00)	0.889 (1.00)	0.283 (1.00)	0.652 (1.00)	0.766 (1.00)	1 (1.00)	1 (1.00)
20p gain	5 (13%)	34	0.00108 (0.408)	0.333 (1.00)	0.313 (1.00)	1 (1.00)	0.767 (1.00)	1 (1.00)	1 (1.00)
20q gain	6 (15%)	33	0.404 (1.00)	0.969 (1.00)	0.254 (1.00)	1 (1.00)	0.616 (1.00)	0.462 (1.00)	0.308 (1.00)
21q gain	4 (10%)	35	0.0146 (1.00)	0.219 (1.00)	0.87 (1.00)	1 (1.00)	0.768 (1.00)	1 (1.00)	1 (1.00)
1p loss	6 (15%)	33	0.779 (1.00)	0.815 (1.00)	0.817 (1.00)	0.528 (1.00)	0.317 (1.00)	1 (1.00)	0.636 (1.00)
2p loss	3 (8%)	36	0.151 (1.00)	0.979 (1.00)	1 (1.00)	0.776 (1.00)	1 (1.00)	1 (1.00)	0.156 (1.00)
2q loss	3 (8%)	36	0.14 (1.00)	0.224 (1.00)	1 (1.00)	0.779 (1.00)	1 (1.00)	1 (1.00)	0.0131 (1.00)
3p loss	3 (8%)	36	0.0313 (1.00)	0.526 (1.00)	0.233 (1.00)	0.776 (1.00)		0.506 (1.00)	0.556 (1.00)
4p loss	18 (46%)	21	0.147 (1.00)	0.247 (1.00)	0.266 (1.00)	0.911 (1.00)	0.451 (1.00)	0.488 (1.00)	0.465 (1.00)
4q loss	16 (41%)	23	0.235 (1.00)	0.241 (1.00)	0.391 (1.00)	0.909 (1.00)	0.594 (1.00)	0.209 (1.00)	0.264 (1.00)
5q loss	3 (8%)	36	0.3 (1.00)	0.692 (1.00)	1 (1.00)	1 (1.00)	0.431 (1.00)	1 (1.00)	0.556 (1.00)
6p loss	5 (13%)	34	0.00205 (0.776)	0.023 (1.00)	0.0535 (1.00)	0.305 (1.00)	1 (1.00)	1 (1.00)	0.302 (1.00)
6q loss	13 (33%)	26	0.826 (1.00)	1 (1.00)	0.0634 (1.00)	0.746 (1.00)	0.101 (1.00)	0.835 (1.00)	0.445 (1.00)
8p loss	4 (10%)	35	0.11 (1.00)	0.43 (1.00)	0.0284 (1.00)	0.218 (1.00)	0.764 (1.00)	0.619 (1.00)	1 (1.00)
9p loss	14 (36%)	25	0.0492 (1.00)	0.271 (1.00)	0.34 (1.00)	0.121 (1.00)	0.748 (1.00)	0.832 (1.00)	0.279 (1.00)
9q loss	12 (31%)	27	0.111 (1.00)	0.626 (1.00)	0.327 (1.00)	0.669 (1.00)	0.2 (1.00)	1 (1.00)	0.693 (1.00)
10p loss	10 (26%)	29	0.0666 (1.00)	0.772 (1.00)	0.567 (1.00)	0.343 (1.00)	1 (1.00)	0.137 (1.00)	0.402 (1.00)
10q loss	9 (23%)	30	0.0258 (1.00)	0.581 (1.00)	0.62 (1.00)	0.69 (1.00)	0.589 (1.00)	0.443 (1.00)	1 (1.00)
11p loss	3 (8%)	36	0.095 (1.00)	0.0175 (1.00)	0.0122 (1.00)	0.0763 (1.00)		0.508 (1.00)	0.556 (1.00)
13q loss	20 (51%)	19	0.114 (1.00)	0.278 (1.00)	0.801 (1.00)	0.7 (1.00)	0.0976 (1.00)	0.0733 (1.00)	0.48 (1.00)
14q loss	15 (38%)	24	0.273 (1.00)	0.347 (1.00)	0.512 (1.00)	0.39 (1.00)	0.88 (1.00)	0.365 (1.00)	0.141 (1.00)
15q loss	7 (18%)	32	0.0547 (1.00)	0.7 (1.00)	0.137 (1.00)	0.649 (1.00)	0.639 (1.00)	0.543 (1.00)	0.653 (1.00)
16p loss	5 (13%)	34	0.0153 (1.00)	0.0882 (1.00)	0.207 (1.00)	0.303 (1.00)	0.447 (1.00)	1 (1.00)	1 (1.00)
16q loss	6 (15%)	33	0.0274 (1.00)	0.507 (1.00)	0.254 (1.00)	0.619 (1.00)	0.803 (1.00)	1 (1.00)	0.636 (1.00)
17p loss	9 (23%)	30	0.676 (1.00)	0.867 (1.00)	0.619 (1.00)	1 (1.00)	0.0657 (1.00)	0.777 (1.00)	0.4 (1.00)
18p loss	5 (13%)	34	0.203 (1.00)	0.628 (1.00)	0.637 (1.00)	0.829 (1.00)	0.45 (1.00)	1 (1.00)	1 (1.00)
18q loss	7 (18%)	32	0.282 (1.00)	0.769 (1.00)	0.944 (1.00)	0.41 (1.00)	0.408 (1.00)	1 (1.00)	0.344 (1.00)
19q loss	3 (8%)	36	0.371 (1.00)	0.476 (1.00)	0.0447 (1.00)	0.384 (1.00)		0.00297 (1.00)	0.556 (1.00)
20p loss	7 (18%)	32	0.365 (1.00)	0.409 (1.00)	0.251 (1.00)	0.748 (1.00)	0.275 (1.00)	0.541 (1.00)	0.653 (1.00)
21q loss	5 (13%)	34	0.127 (1.00)	0.72 (1.00)	0.0437 (1.00)	0.375 (1.00)	0.765 (1.00)	0.381 (1.00)	1 (1.00)
22q loss	31 (79%)	8	0.768 (1.00)	0.486 (1.00)	0.532 (1.00)	0.259 (1.00)	0.681 (1.00)	0.209 (1.00)	1 (1.00)
xq loss	12 (31%)	27	0.361 (1.00)	0.807 (1.00)	0.438 (1.00)	0.203 (1.00)	0.565 (1.00)	0.679 (1.00)	0.693 (1.00)

'11q loss' versus 'Time to Death'

P value = 4.41e-05 (logrank test), Q value = 0.017

Table S1. Gene #41: '11q loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	39	29	0.2 - 91.7 (13.3)
11Q LOSS MUTATED	4	4	0.2 - 6.1 (4.4)
11Q LOSS WILD-TYPE	35	25	1.6 - 91.7 (14.3)

Figure S1. Get High-res Image Gene #41: '11q loss' versus Clinical Feature #1: 'Time to Death'

'17q loss' versus 'Time to Death'

P value = 0.000236 (logrank test), Q value = 0.09

Table S2. Gene #48: '17q loss' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	39	29	0.2 - 91.7 (13.3)
17Q LOSS MUTATED	3	3	0.2 - 8.0 (2.5)
17Q LOSS WILD-TYPE	36	26	1.6 - 91.7 (13.9)

Figure S2. Get High-res Image Gene #48: '17q loss' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = MESO-TP.merged_data.txt
Number of patients = 39
Number of significantly arm-level cnvs = 55
Number of selected clinical features = 7
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

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] 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)

[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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