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

Sarcoma (Primary solid tumor)

15 July 2014 | analyses__2014_07_15

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/C14748N2

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 61 focal events and 4 clinical features across 114 patients, 3 significant findings detected with Q value < 0.25.

amp_7q31.1 cnv correlated to 'AGE'.
del_2p25.3 cnv correlated to 'GENDER'.
del_19p13.3 cnv correlated to 'GENDER'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 61 focal events and 4 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER	RACE
	nCNV (%)	nWild-Type	logrank test	Wilcoxon-test	Fisher's exact test	Fisher's exact test
amp 7q31 1	31 (27%)	83	0.371 (1.00)	1.77e-05 (0.00433)	1 (1.00)	0.556 (1.00)
del 2p25 3	38 (33%)	76	0.409 (1.00)	0.145 (1.00)	0.000275 (0.0668)	0.429 (1.00)
del 19p13 3	33 (29%)	81	0.321 (1.00)	0.418 (1.00)	0.000897 (0.217)	1 (1.00)
amp 1p32 1	36 (32%)	78	0.126 (1.00)	0.52 (1.00)	0.55 (1.00)	0.461 (1.00)
amp 1q24 3	45 (39%)	69	0.937 (1.00)	0.4 (1.00)	0.571 (1.00)	0.898 (1.00)
amp 3p11 2	25 (22%)	89	0.229 (1.00)	0.0186 (1.00)	0.502 (1.00)	1 (1.00)
amp 5p15 2	47 (41%)	67	0.0155 (1.00)	0.0201 (1.00)	0.252 (1.00)	0.347 (1.00)
amp 6p21 1	26 (23%)	88	0.119 (1.00)	0.0102 (1.00)	0.263 (1.00)	0.438 (1.00)
amp 6q24 3	32 (28%)	82	0.435 (1.00)	0.0245 (1.00)	0.209 (1.00)	1 (1.00)
amp 8q21 12	42 (37%)	72	0.0253 (1.00)	0.124 (1.00)	1 (1.00)	0.138 (1.00)
amp 11q22 2	17 (15%)	97	0.984 (1.00)	0.968 (1.00)	1 (1.00)	0.746 (1.00)
amp 12p13 32	21 (18%)	93	0.0961 (1.00)	0.0897 (1.00)	0.629 (1.00)	1 (1.00)
amp 12p12 1	25 (22%)	89	0.169 (1.00)	0.00162 (0.391)	1 (1.00)	1 (1.00)
amp 12q15	46 (40%)	68	0.68 (1.00)	0.0888 (1.00)	0.0233 (1.00)	0.088 (1.00)
amp 13q34	19 (17%)	95	0.333 (1.00)	0.629 (1.00)	0.0797 (1.00)	0.315 (1.00)
amp 17p11 2	38 (33%)	76	0.208 (1.00)	0.151 (1.00)	0.111 (1.00)	0.374 (1.00)
amp 17q24 3	29 (25%)	85	0.0114 (1.00)	0.0805 (1.00)	0.00227 (0.545)	0.568 (1.00)
amp 19p13 2	39 (34%)	75	0.829 (1.00)	0.568 (1.00)	0.694 (1.00)	0.6 (1.00)
amp 19q12	37 (32%)	77	0.131 (1.00)	0.00866 (1.00)	0.841 (1.00)	1 (1.00)
amp 20q13 33	42 (37%)	72	0.314 (1.00)	0.0319 (1.00)	0.0794 (1.00)	0.886 (1.00)
amp 21q21 1	33 (29%)	81	0.325 (1.00)	0.0926 (1.00)	0.534 (1.00)	1 (1.00)
amp xp21 2	36 (32%)	78	0.716 (1.00)	0.985 (1.00)	0.225 (1.00)	0.676 (1.00)
amp xq21 2	18 (16%)	96	0.0132 (1.00)	0.807 (1.00)	1 (1.00)	0.773 (1.00)
del 1p36 32	36 (32%)	78	0.0217 (1.00)	0.37 (1.00)	0.105 (1.00)	0.7 (1.00)
del 1p32 3	18 (16%)	96	0.0344 (1.00)	0.547 (1.00)	0.039 (1.00)	0.0186 (1.00)
del 1q44	31 (27%)	83	0.486 (1.00)	0.42 (1.00)	0.404 (1.00)	0.485 (1.00)
del 2q37 3	41 (36%)	73	0.0429 (1.00)	0.561 (1.00)	0.331 (1.00)	0.793 (1.00)
del 2q37 3	43 (38%)	71	0.216 (1.00)	0.33 (1.00)	0.179 (1.00)	0.798 (1.00)
del 3p21 31	21 (18%)	93	0.257 (1.00)	0.0143 (1.00)	0.478 (1.00)	0.048 (1.00)
del 3q29	26 (23%)	88	0.351 (1.00)	0.723 (1.00)	0.658 (1.00)	0.613 (1.00)
del 4q35 1	38 (33%)	76	0.114 (1.00)	0.0635 (1.00)	0.691 (1.00)	0.206 (1.00)
del 6p25 1	40 (35%)	74	0.731 (1.00)	0.445 (1.00)	0.433 (1.00)	0.181 (1.00)
del 6q14 1	26 (23%)	88	0.115 (1.00)	0.845 (1.00)	0.824 (1.00)	0.657 (1.00)
del 6q16 1	23 (20%)	91	0.385 (1.00)	0.385 (1.00)	0.349 (1.00)	0.729 (1.00)
del 7q36 3	25 (22%)	89	0.221 (1.00)	0.468 (1.00)	0.823 (1.00)	0.353 (1.00)
del 8p23 3	34 (30%)	80	0.508 (1.00)	0.906 (1.00)	0.546 (1.00)	1 (1.00)
del 9p23	37 (32%)	77	0.81 (1.00)	0.0437 (1.00)	0.548 (1.00)	1 (1.00)
del 9p21 3	47 (41%)	67	0.764 (1.00)	0.0097 (1.00)	0.445 (1.00)	0.484 (1.00)
del 9q34 3	27 (24%)	87	0.0374 (1.00)	0.936 (1.00)	0.379 (1.00)	0.0551 (1.00)
del 10p15 3	58 (51%)	56	0.579 (1.00)	0.372 (1.00)	0.132 (1.00)	0.712 (1.00)
del 10q23 31	64 (56%)	50	0.298 (1.00)	0.587 (1.00)	0.00813 (1.00)	0.38 (1.00)
del 11p15 5	47 (41%)	67	0.287 (1.00)	0.00508 (1.00)	0.703 (1.00)	0.624 (1.00)
del 11q24 3	46 (40%)	68	0.138 (1.00)	0.0117 (1.00)	0.451 (1.00)	0.63 (1.00)
del 12p13 1	33 (29%)	81	0.843 (1.00)	0.628 (1.00)	0.3 (1.00)	1 (1.00)
del 12q12	22 (19%)	92	0.899 (1.00)	0.682 (1.00)	1 (1.00)	0.67 (1.00)
del 13q14 2	79 (69%)	35	0.129 (1.00)	0.0137 (1.00)	0.0445 (1.00)	0.271 (1.00)
del 14q24 1	37 (32%)	77	0.153 (1.00)	0.781 (1.00)	0.548 (1.00)	1 (1.00)
del 15q11 2	19 (17%)	95	0.396 (1.00)	0.164 (1.00)	0.0797 (1.00)	0.594 (1.00)
del 16q12 1	63 (55%)	51	0.151 (1.00)	0.266 (1.00)	0.038 (1.00)	0.891 (1.00)
del 16q23 1	64 (56%)	50	0.298 (1.00)	0.049 (1.00)	0.0593 (1.00)	1 (1.00)
del 17p13 1	50 (44%)	64	0.897 (1.00)	0.664 (1.00)	0.0371 (1.00)	0.717 (1.00)
del 17q11 2	28 (25%)	86	0.129 (1.00)	0.323 (1.00)	0.828 (1.00)	1 (1.00)
del 17q25 3	29 (25%)	85	0.31 (1.00)	0.158 (1.00)	0.282 (1.00)	0.413 (1.00)
del 18q23	35 (31%)	79	0.34 (1.00)	0.0147 (1.00)	0.541 (1.00)	0.764 (1.00)
del 19q13 43	41 (36%)	73	0.704 (1.00)	0.694 (1.00)	0.0793 (1.00)	0.552 (1.00)
del 21q11 2	20 (18%)	94	0.944 (1.00)	0.293 (1.00)	0.629 (1.00)	0.173 (1.00)
del 21q22 3	31 (27%)	83	0.69 (1.00)	0.00334 (0.799)	0.677 (1.00)	1 (1.00)
del 22q13 31	38 (33%)	76	0.443 (1.00)	0.449 (1.00)	0.0458 (1.00)	0.531 (1.00)
del xp22 33	35 (31%)	79	0.157 (1.00)	0.0337 (1.00)	0.153 (1.00)	0.468 (1.00)
del xq21 1	57 (50%)	57	0.198 (1.00)	0.215 (1.00)	0.0141 (1.00)	0.628 (1.00)
del xq27 1	57 (50%)	57	0.501 (1.00)	0.881 (1.00)	0.0381 (1.00)	0.4 (1.00)

'amp_7q31.1' versus 'AGE'

P value = 1.77e-05 (Wilcoxon-test), Q value = 0.0043

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

	nPatients	Mean (Std.Dev)
ALL	114	61.3 (14.1)
AMP PEAK 7(7Q31.1) MUTATED	31	69.6 (11.4)
AMP PEAK 7(7Q31.1) WILD-TYPE	83	58.2 (13.8)

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

'del_2p25.3' versus 'GENDER'

P value = 0.000275 (Fisher's exact test), Q value = 0.067

Table S2. Gene #25: 'del_2p25.3' versus Clinical Feature #3: 'GENDER'

nPatients	FEMALE	MALE
ALL	62	52
DEL PEAK 4(2P25.3) MUTATED	30	8
DEL PEAK 4(2P25.3) WILD-TYPE	32	44

Figure S2. Get High-res Image Gene #25: 'del_2p25.3' versus Clinical Feature #3: 'GENDER'

'del_19p13.3' versus 'GENDER'

P value = 0.000897 (Fisher's exact test), Q value = 0.22

Table S3. Gene #54: 'del_19p13.3' versus Clinical Feature #3: 'GENDER'

nPatients	FEMALE	MALE
ALL	62	52
DEL PEAK 33(19P13.3) MUTATED	26	7
DEL PEAK 33(19P13.3) WILD-TYPE	36	45

Figure S3. Get High-res Image Gene #54: 'del_19p13.3' versus Clinical Feature #3: 'GENDER'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = SARC-TP.merged_data.txt
Number of patients = 114
Number of significantly focal cnvs = 61
Number of selected clinical features = 4
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

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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