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

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 20 focal events and 5 clinical features across 191 patients, 11 significant findings detected with Q value < 0.25.

amp_1q43 cnv correlated to 'YEARS_TO_BIRTH'.
amp_11q23.3 cnv correlated to 'YEARS_TO_BIRTH'.
amp_21q22.2 cnv correlated to 'Time to Death' and 'YEARS_TO_BIRTH'.
del_3p13 cnv correlated to 'Time to Death'.
del_5q31.2 cnv correlated to 'Time to Death' and 'YEARS_TO_BIRTH'.
del_12p13.2 cnv correlated to 'Time to Death'.
del_17q11.2 cnv correlated to 'Time to Death'.
del_18p11.21 cnv correlated to 'Time to Death'.
del_20q13.13 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 20 focal events and 5 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 11 significant findings detected.


		Clinical Features	Time to Death	YEARS TO BIRTH	GENDER	RACE	ETHNICITY
	nCNV (%)	nWild-Type	logrank test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Fisher's exact test
amp 21q22 2	14 (7%)	177	0.00622 (0.19)	0.0236 (0.215)	0.0922 (0.464)	0.383 (0.782)	1 (1.00)
del 5q31 2	18 (9%)	173	0.0179 (0.209)	0.0108 (0.19)	0.0464 (0.357)	1 (1.00)	1 (1.00)
amp 1q43	7 (4%)	184	0.194 (0.613)	0.0209 (0.209)	1 (1.00)	1 (1.00)	1 (1.00)
amp 11q23 3	17 (9%)	174	0.137 (0.527)	0.0171 (0.209)	0.45 (0.865)	1 (1.00)	0.249 (0.663)
del 3p13	8 (4%)	183	0.000606 (0.0606)	0.112 (0.485)	0.295 (0.74)	0.0976 (0.464)	1 (1.00)
del 12p13 2	10 (5%)	181	0.00127 (0.0636)	0.367 (0.781)	0.351 (0.781)	1 (1.00)	1 (1.00)
del 17q11 2	13 (7%)	178	0.0103 (0.19)	0.321 (0.764)	0.775 (1.00)	0.652 (1.00)	1 (1.00)
del 18p11 21	9 (5%)	182	0.0199 (0.209)	0.427 (0.838)	0.185 (0.613)	0.557 (0.963)	1 (1.00)
del 20q13 13	4 (2%)	187	0.0114 (0.19)	0.0674 (0.397)	0.627 (1.00)	0.3 (0.74)	1 (1.00)
amp 1p33	7 (4%)	184	0.202 (0.613)	0.119 (0.497)	1 (1.00)	1 (1.00)	1 (1.00)
amp 13q31 3	7 (4%)	184	0.84 (1.00)	0.0648 (0.397)	1 (1.00)	1 (1.00)	1 (1.00)
amp 19p13 2	6 (3%)	185	0.701 (1.00)	0.793 (1.00)	0.223 (0.655)	1 (1.00)	1 (1.00)
amp 20q11 21	3 (2%)	188	0.184 (0.613)	0.346 (0.781)	0.252 (0.663)	0.234 (0.663)	1 (1.00)
del 7p12 1	16 (8%)	175	0.166 (0.613)	0.484 (0.914)	0.604 (1.00)	1 (1.00)	1 (1.00)
del 7q34	24 (13%)	167	0.102 (0.464)	0.197 (0.613)	0.512 (0.917)	0.769 (1.00)	1 (1.00)
del 7q34	24 (13%)	167	0.102 (0.464)	0.197 (0.613)	0.512 (0.917)	0.769 (1.00)	1 (1.00)
del 9q21 32	5 (3%)	186	0.735 (1.00)	0.417 (0.834)	0.378 (0.782)	0.364 (0.781)	1 (1.00)
del 12q21 33	3 (2%)	188	0.367 (0.781)	0.0366 (0.305)	0.252 (0.663)	1 (1.00)	1 (1.00)
del 16q23 1	9 (5%)	182	0.0992 (0.464)	0.304 (0.74)	0.513 (0.917)	0.559 (0.963)	1 (1.00)
del 17p13 2	15 (8%)	176	0.0528 (0.377)	0.129 (0.516)	0.0565 (0.377)	0.671 (1.00)	1 (1.00)

'amp_1q43' versus 'YEARS_TO_BIRTH'

P value = 0.0209 (Wilcoxon-test), Q value = 0.21

Table S1. Gene #2: 'amp_1q43' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	191	55.2 (16.1)
AMP PEAK 2(1Q43) MUTATED	7	67.6 (11.3)
AMP PEAK 2(1Q43) WILD-TYPE	184	54.8 (16.1)

Figure S1. Get High-res Image Gene #2: 'amp_1q43' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'amp_11q23.3' versus 'YEARS_TO_BIRTH'

P value = 0.0171 (Wilcoxon-test), Q value = 0.21

Table S2. Gene #3: 'amp_11q23.3' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	191	55.2 (16.1)
AMP PEAK 3(11Q23.3) MUTATED	17	63.3 (12.1)
AMP PEAK 3(11Q23.3) WILD-TYPE	174	54.4 (16.2)

Figure S2. Get High-res Image Gene #3: 'amp_11q23.3' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'amp_21q22.2' versus 'Time to Death'

P value = 0.00622 (logrank test), Q value = 0.19

Table S3. Gene #7: 'amp_21q22.2' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	178	116	0.0 - 94.1 (11.0)
AMP PEAK 7(21Q22.2) MUTATED	12	10	1.0 - 24.0 (5.5)
AMP PEAK 7(21Q22.2) WILD-TYPE	166	106	0.0 - 94.1 (12.0)

Figure S3. Get High-res Image Gene #7: 'amp_21q22.2' versus Clinical Feature #1: 'Time to Death'

'amp_21q22.2' versus 'YEARS_TO_BIRTH'

P value = 0.0236 (Wilcoxon-test), Q value = 0.21

Table S4. Gene #7: 'amp_21q22.2' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	191	55.2 (16.1)
AMP PEAK 7(21Q22.2) MUTATED	14	63.7 (16.7)
AMP PEAK 7(21Q22.2) WILD-TYPE	177	54.6 (15.9)

Figure S4. Get High-res Image Gene #7: 'amp_21q22.2' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'del_3p13' versus 'Time to Death'

P value = 0.000606 (logrank test), Q value = 0.061

Table S5. Gene #8: 'del_3p13' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	178	116	0.0 - 94.1 (11.0)
DEL PEAK 2(3P13) MUTATED	8	7	0.0 - 14.0 (1.5)
DEL PEAK 2(3P13) WILD-TYPE	170	109	0.0 - 94.1 (12.0)

Figure S5. Get High-res Image Gene #8: 'del_3p13' versus Clinical Feature #1: 'Time to Death'

'del_5q31.2' versus 'Time to Death'

P value = 0.0179 (logrank test), Q value = 0.21

Table S6. Gene #9: 'del_5q31.2' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	178	116	0.0 - 94.1 (11.0)
DEL PEAK 3(5Q31.2) MUTATED	17	15	1.0 - 73.0 (10.0)
DEL PEAK 3(5Q31.2) WILD-TYPE	161	101	0.0 - 94.1 (12.0)

Figure S6. Get High-res Image Gene #9: 'del_5q31.2' versus Clinical Feature #1: 'Time to Death'

'del_5q31.2' versus 'YEARS_TO_BIRTH'

P value = 0.0108 (Wilcoxon-test), Q value = 0.19

Table S7. Gene #9: 'del_5q31.2' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	191	55.2 (16.1)
DEL PEAK 3(5Q31.2) MUTATED	18	64.3 (13.0)
DEL PEAK 3(5Q31.2) WILD-TYPE	173	54.3 (16.1)

Figure S7. Get High-res Image Gene #9: 'del_5q31.2' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'del_12p13.2' versus 'Time to Death'

P value = 0.00127 (logrank test), Q value = 0.064

Table S8. Gene #14: 'del_12p13.2' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	178	116	0.0 - 94.1 (11.0)
DEL PEAK 10(12P13.2) MUTATED	9	9	0.0 - 22.1 (7.0)
DEL PEAK 10(12P13.2) WILD-TYPE	169	107	0.0 - 94.1 (12.0)

Figure S8. Get High-res Image Gene #14: 'del_12p13.2' versus Clinical Feature #1: 'Time to Death'

'del_17q11.2' versus 'Time to Death'

P value = 0.0103 (logrank test), Q value = 0.19

Table S9. Gene #18: 'del_17q11.2' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	178	116	0.0 - 94.1 (11.0)
DEL PEAK 14(17Q11.2) MUTATED	12	11	0.0 - 49.0 (4.5)
DEL PEAK 14(17Q11.2) WILD-TYPE	166	105	0.0 - 94.1 (11.5)

Figure S9. Get High-res Image Gene #18: 'del_17q11.2' versus Clinical Feature #1: 'Time to Death'

'del_18p11.21' versus 'Time to Death'

P value = 0.0199 (logrank test), Q value = 0.21

Table S10. Gene #19: 'del_18p11.21' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	178	116	0.0 - 94.1 (11.0)
DEL PEAK 15(18P11.21) MUTATED	8	8	1.0 - 17.0 (9.5)
DEL PEAK 15(18P11.21) WILD-TYPE	170	108	0.0 - 94.1 (11.5)

Figure S10. Get High-res Image Gene #19: 'del_18p11.21' versus Clinical Feature #1: 'Time to Death'

'del_20q13.13' versus 'Time to Death'

P value = 0.0114 (logrank test), Q value = 0.19

Table S11. Gene #20: 'del_20q13.13' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	178	116	0.0 - 94.1 (11.0)
DEL PEAK 16(20Q13.13) MUTATED	4	4	0.0 - 10.0 (7.0)
DEL PEAK 16(20Q13.13) WILD-TYPE	174	112	0.0 - 94.1 (12.0)

Figure S11. Get High-res Image Gene #20: 'del_20q13.13' versus Clinical Feature #1: 'Time to Death'

Methods & Data

Input

Copy number data file = all_lesions.txt from GISTIC pipeline
Processed Copy number data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/LAML-TB/19782150/transformed.cor.cli.txt
Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/LAML-TB/19775300/LAML-TB.merged_data.txt
Number of patients = 191
Number of significantly focal cnvs = 20
Number of selected clinical features = 5
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.

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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