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

Acute Myeloid Leukemia (Primary blood derived cancer - Peripheral blood)

23 September 2013 | analyses__2013_09_23

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 (2013): Correlation between copy number variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C18G8J2X

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 30 arm-level events and 3 clinical features across 191 patients, 6 significant findings detected with Q value < 0.25.

3P LOSS MUTATION ANALYSIS cnv correlated to 'AGE'.
3Q LOSS MUTATION ANALYSIS cnv correlated to 'AGE'.
5Q LOSS MUTATION ANALYSIS cnv correlated to 'Time to Death'.
18P LOSS MUTATION ANALYSIS cnv correlated to 'Time to Death'.
18Q LOSS 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 30 arm-level events and 3 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 6 significant findings detected.


		Clinical Features	Time to Death	AGE	GENDER
	nCNV (%)	nWild-Type	logrank test	t-test	Fisher's exact test
18Q LOSS MUTATION ANALYSIS	4 (2%)	187	0.000715 (0.0586)	0.003 (0.234)	0.127 (1.00)
3P LOSS MUTATION ANALYSIS	3 (2%)	188		0.00241 (0.193)	0.252 (1.00)
3Q LOSS MUTATION ANALYSIS	3 (2%)	188		0.00241 (0.193)	0.252 (1.00)
5Q LOSS MUTATION ANALYSIS	6 (3%)	185	0.000679 (0.0563)	0.0601 (1.00)	0.0325 (1.00)
18P LOSS MUTATION ANALYSIS	5 (3%)	186	0.00184 (0.149)	0.355 (1.00)	0.0642 (1.00)
1P GAIN MUTATION ANALYSIS	3 (2%)	188		0.0913 (1.00)	0.592 (1.00)
4P GAIN MUTATION ANALYSIS	4 (2%)	187	0.599 (1.00)	0.425 (1.00)	0.627 (1.00)
4Q GAIN MUTATION ANALYSIS	4 (2%)	187	0.599 (1.00)	0.425 (1.00)	0.627 (1.00)
8P GAIN MUTATION ANALYSIS	22 (12%)	169	0.479 (1.00)	0.072 (1.00)	0.0734 (1.00)
8Q GAIN MUTATION ANALYSIS	23 (12%)	168	0.523 (1.00)	0.106 (1.00)	0.0723 (1.00)
10Q GAIN MUTATION ANALYSIS	3 (2%)	188		0.947 (1.00)	0.252 (1.00)
11P GAIN MUTATION ANALYSIS	4 (2%)	187		0.188 (1.00)	1 (1.00)
11Q GAIN MUTATION ANALYSIS	7 (4%)	184	0.553 (1.00)	0.0154 (1.00)	1 (1.00)
13Q GAIN MUTATION ANALYSIS	6 (3%)	185	0.802 (1.00)	0.143 (1.00)	0.69 (1.00)
17Q GAIN MUTATION ANALYSIS	3 (2%)	188	0.713 (1.00)	0.29 (1.00)	1 (1.00)
19P GAIN MUTATION ANALYSIS	6 (3%)	185	0.958 (1.00)	0.99 (1.00)	0.223 (1.00)
19Q GAIN MUTATION ANALYSIS	6 (3%)	185	0.958 (1.00)	0.99 (1.00)	0.223 (1.00)
21Q GAIN MUTATION ANALYSIS	8 (4%)	183	0.0165 (1.00)	0.616 (1.00)	0.0732 (1.00)
22Q GAIN MUTATION ANALYSIS	9 (5%)	182	0.707 (1.00)	0.0339 (1.00)	0.513 (1.00)
XQ GAIN MUTATION ANALYSIS	3 (2%)	188		0.0894 (1.00)	1 (1.00)
7P LOSS MUTATION ANALYSIS	17 (9%)	174	0.0748 (1.00)	0.171 (1.00)	0.802 (1.00)
7Q LOSS MUTATION ANALYSIS	20 (10%)	171	0.0352 (1.00)	0.18 (1.00)	1 (1.00)
12P LOSS MUTATION ANALYSIS	4 (2%)	187		0.752 (1.00)	0.627 (1.00)
15Q LOSS MUTATION ANALYSIS	4 (2%)	187	0.656 (1.00)	0.277 (1.00)	1 (1.00)
16Q LOSS MUTATION ANALYSIS	4 (2%)	187	0.0587 (1.00)	0.365 (1.00)	0.627 (1.00)
17P LOSS MUTATION ANALYSIS	13 (7%)	178	0.0993 (1.00)	0.783 (1.00)	0.147 (1.00)
17Q LOSS MUTATION ANALYSIS	7 (4%)	184	0.385 (1.00)	0.164 (1.00)	0.458 (1.00)
19P LOSS MUTATION ANALYSIS	4 (2%)	187	0.0509 (1.00)	0.0534 (1.00)	1 (1.00)
19Q LOSS MUTATION ANALYSIS	4 (2%)	187	0.0509 (1.00)	0.0534 (1.00)	1 (1.00)
XQ LOSS MUTATION ANALYSIS	5 (3%)	186	0.174 (1.00)	0.0197 (1.00)	0.0642 (1.00)

'3P LOSS MUTATION STATUS' versus 'AGE'

P value = 0.00241 (t-test), Q value = 0.19

Table S1. Gene #16: '3P LOSS MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	191	55.2 (16.1)
3P LOSS MUTATED	3	74.0 (3.6)
3P LOSS WILD-TYPE	188	54.9 (16.0)

Figure S1. Get High-res Image Gene #16: '3P LOSS MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'3Q LOSS MUTATION STATUS' versus 'AGE'

P value = 0.00241 (t-test), Q value = 0.19

Table S2. Gene #17: '3Q LOSS MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	191	55.2 (16.1)
3Q LOSS MUTATED	3	74.0 (3.6)
3Q LOSS WILD-TYPE	188	54.9 (16.0)

Figure S2. Get High-res Image Gene #17: '3Q LOSS MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'5Q LOSS MUTATION STATUS' versus 'Time to Death'

P value = 0.000679 (logrank test), Q value = 0.056

Table S3. Gene #18: '5Q LOSS MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	166	104	0.9 - 94.1 (12.0)
5Q LOSS MUTATED	6	6	1.0 - 12.0 (7.0)
5Q LOSS WILD-TYPE	160	98	0.9 - 94.1 (12.5)

Figure S3. Get High-res Image Gene #18: '5Q LOSS MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'18P LOSS MUTATION STATUS' versus 'Time to Death'

P value = 0.00184 (logrank test), Q value = 0.15

Table S4. Gene #26: '18P LOSS MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	166	104	0.9 - 94.1 (12.0)
18P LOSS MUTATED	5	5	1.0 - 12.0 (7.0)
18P LOSS WILD-TYPE	161	99	0.9 - 94.1 (12.0)

Figure S4. Get High-res Image Gene #26: '18P LOSS MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'18Q LOSS MUTATION STATUS' versus 'Time to Death'

P value = 0.000715 (logrank test), Q value = 0.059

Table S5. Gene #27: '18Q LOSS MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	166	104	0.9 - 94.1 (12.0)
18Q LOSS MUTATED	4	4	1.0 - 10.0 (4.5)
18Q LOSS WILD-TYPE	162	100	0.9 - 94.1 (12.0)

Figure S5. Get High-res Image Gene #27: '18Q LOSS MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'18Q LOSS MUTATION STATUS' versus 'AGE'

P value = 0.003 (t-test), Q value = 0.23

Table S6. Gene #27: '18Q LOSS MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	191	55.2 (16.1)
18Q LOSS MUTATED	4	72.8 (5.4)
18Q LOSS WILD-TYPE	187	54.8 (16.0)

Figure S6. Get High-res Image Gene #27: '18Q LOSS MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = LAML-TB.clin.merged.picked.txt
Number of patients = 191
Number of significantly arm-level cnvs = 30
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.

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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