Correlation between copy number variation genes (focal events) and molecular subtypes

Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (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 variation genes (focal events) and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1J1021N

Overview

Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and molecular subtypes.

Summary

Testing the association between copy number variation 40 focal events and 8 molecular subtypes across 48 patients, 3 significant findings detected with P value < 0.05 and Q value < 0.25.

amp_2p16.1 cnv correlated to 'METHLYATION_CNMF'.
amp_7p22.3 cnv correlated to 'CN_CNMF'.
amp_7q21.3 cnv correlated to 'CN_CNMF'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 40 focal events and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 3 significant findings detected.


		Clinical Features	CN CNMF	METHLYATION CNMF	MRNASEQ CNMF	MRNASEQ CHIERARCHICAL	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL	MIRSEQ MATURE CNMF	MIRSEQ MATURE CHIERARCHICAL
	nCNV (%)	nWild-Type	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
amp 2p16 1	16 (33%)	32	0.124 (1.00)	0.000509 (0.158)	0.686 (1.00)	0.75 (1.00)	0.0574 (1.00)	0.0126 (1.00)	0.335 (1.00)	0.469 (1.00)
amp 7p22 3	16 (33%)	32	7.62e-05 (0.0238)	0.359 (1.00)	1 (1.00)	0.652 (1.00)	0.924 (1.00)	0.887 (1.00)	1 (1.00)	0.124 (1.00)
amp 7q21 3	15 (31%)	33	1.04e-05 (0.00325)	1 (1.00)	0.67 (1.00)	0.121 (1.00)	0.513 (1.00)	0.888 (1.00)	0.742 (1.00)	0.44 (1.00)
amp 1q24 2	16 (33%)	32	0.00524 (1.00)	1 (1.00)	0.41 (1.00)	0.226 (1.00)	0.776 (1.00)	0.458 (1.00)	1 (1.00)	1 (1.00)
amp 3q27 3	14 (29%)	34	0.008 (1.00)	0.341 (1.00)	0.396 (1.00)	0.72 (1.00)	0.71 (1.00)	0.291 (1.00)	0.516 (1.00)	0.373 (1.00)
amp 3q29	15 (31%)	33	0.00324 (0.998)	0.212 (1.00)	0.655 (1.00)	1 (1.00)	0.88 (1.00)	0.296 (1.00)	1 (1.00)	0.204 (1.00)
amp 5p13 1	8 (17%)	40	1 (1.00)	0.701 (1.00)	1 (1.00)		0.451 (1.00)	0.591 (1.00)	0.673 (1.00)	0.187 (1.00)
amp 8q24 23	14 (29%)	34	1 (1.00)	0.752 (1.00)	0.639 (1.00)	0.676 (1.00)	0.49 (1.00)	0.197 (1.00)	0.726 (1.00)	0.344 (1.00)
amp 12q21 1	14 (29%)	34	0.517 (1.00)	0.0243 (1.00)	1 (1.00)	0.123 (1.00)	0.68 (1.00)	0.0725 (1.00)	0.323 (1.00)	0.729 (1.00)
amp 16p12 2	10 (21%)	38	0.00818 (1.00)	0.0723 (1.00)	0.173 (1.00)	0.342 (1.00)	0.0693 (1.00)	0.0479 (1.00)	1 (1.00)	0.616 (1.00)
amp 18q21 2	16 (33%)	32	0.0306 (1.00)	0.76 (1.00)	0.655 (1.00)	1 (1.00)	0.215 (1.00)	0.0296 (1.00)	0.335 (1.00)	0.112 (1.00)
amp 19q13 43	10 (21%)	38	1 (1.00)	0.286 (1.00)	0.583 (1.00)	1 (1.00)	0.269 (1.00)	0.278 (1.00)	0.709 (1.00)	0.0551 (1.00)
amp xq27 3	7 (15%)	41	0.0967 (1.00)	0.0971 (1.00)	0.655 (1.00)	0.704 (1.00)	0.328 (1.00)	0.0812 (1.00)	0.682 (1.00)	0.328 (1.00)
del 1p36 32	11 (23%)	37	0.0155 (1.00)	1 (1.00)	1 (1.00)	0.518 (1.00)	0.554 (1.00)	0.703 (1.00)	1 (1.00)	0.44 (1.00)
del 1p13 1	12 (25%)	36	0.501 (1.00)	0.74 (1.00)	0.67 (1.00)	0.275 (1.00)	0.56 (1.00)	0.763 (1.00)	1 (1.00)	0.577 (1.00)
del 1q43	10 (21%)	38	0.0363 (1.00)	0.724 (1.00)	1 (1.00)	1 (1.00)	0.717 (1.00)	0.841 (1.00)	1 (1.00)	0.612 (1.00)
del 2q23 1	8 (17%)	40	0.236 (1.00)	1 (1.00)	1 (1.00)	0.516 (1.00)	0.779 (1.00)	0.526 (1.00)	0.673 (1.00)	0.62 (1.00)
del 3p21 31	8 (17%)	40	0.451 (1.00)	0.701 (1.00)	0.484 (1.00)		0.234 (1.00)	0.775 (1.00)	0.214 (1.00)	0.444 (1.00)
del 4q35 1	10 (21%)	38	0.487 (1.00)	0.724 (1.00)	0.639 (1.00)	0.544 (1.00)	0.349 (1.00)	0.153 (1.00)	0.149 (1.00)	0.371 (1.00)
del 5q33 3	4 (8%)	44	0.286 (1.00)	0.609 (1.00)	1 (1.00)	0.033 (1.00)	0.255 (1.00)	0.00756 (1.00)	0.313 (1.00)	0.742 (1.00)
del 6p21 32	6 (12%)	42	1 (1.00)	1 (1.00)	0.583 (1.00)	0.761 (1.00)	0.699 (1.00)	0.522 (1.00)	0.644 (1.00)	0.325 (1.00)
del 6q14 1	17 (35%)	31	0.221 (1.00)	0.547 (1.00)	0.435 (1.00)	0.325 (1.00)	0.195 (1.00)	0.178 (1.00)	0.00321 (0.993)	0.121 (1.00)
del 6q22 32	16 (33%)	32	0.759 (1.00)	0.0305 (1.00)	0.396 (1.00)	0.389 (1.00)	0.37 (1.00)	0.368 (1.00)	0.0494 (1.00)	0.107 (1.00)
del 6q23 3	16 (33%)	32	1 (1.00)	0.0305 (1.00)	0.0836 (1.00)	0.0221 (1.00)	0.174 (1.00)	0.168 (1.00)	0.0231 (1.00)	0.258 (1.00)
del 7q33	5 (10%)	43	0.372 (1.00)	1 (1.00)	0.464 (1.00)		0.431 (1.00)	0.18 (1.00)	0.644 (1.00)	0.346 (1.00)
del 8p23 2	12 (25%)	36	0.00616 (1.00)	0.74 (1.00)	0.311 (1.00)	0.354 (1.00)	0.601 (1.00)	0.0811 (1.00)	0.707 (1.00)	0.928 (1.00)
del 8q12 1	9 (19%)	39	0.127 (1.00)	0.461 (1.00)	0.311 (1.00)	0.357 (1.00)	0.498 (1.00)	0.407 (1.00)	1 (1.00)	0.576 (1.00)
del 9p21 3	17 (35%)	31	0.221 (1.00)	0.0145 (1.00)	0.114 (1.00)	0.328 (1.00)	0.00944 (1.00)	0.0297 (1.00)	0.0547 (1.00)	0.108 (1.00)
del 10q23 31	8 (17%)	40	0.236 (1.00)	1 (1.00)	0.639 (1.00)	0.0381 (1.00)	0.0627 (1.00)	0.678 (1.00)	0.428 (1.00)	0.0231 (1.00)
del 12p13 2	8 (17%)	40	0.0446 (1.00)	0.701 (1.00)	1 (1.00)	1 (1.00)	0.662 (1.00)	0.956 (1.00)	1 (1.00)	0.845 (1.00)
del 13q14 2	7 (15%)	41	0.0967 (1.00)	0.416 (1.00)	1 (1.00)	0.762 (1.00)	0.19 (1.00)	0.249 (1.00)	1 (1.00)	0.652 (1.00)
del 15q21 1	13 (27%)	35	0.741 (1.00)	0.517 (1.00)	1 (1.00)	0.653 (1.00)	0.49 (1.00)	0.666 (1.00)	0.726 (1.00)	0.333 (1.00)
del 16p13 13	6 (12%)	42	0.197 (1.00)	0.666 (1.00)	0.311 (1.00)	0.81 (1.00)	0.327 (1.00)	0.0281 (1.00)	0.613 (1.00)	0.63 (1.00)
del 16q23 1	5 (10%)	43	0.0724 (1.00)	1 (1.00)	0.639 (1.00)	0.448 (1.00)	0.0915 (1.00)	0.165 (1.00)	0.114 (1.00)	0.761 (1.00)
del 17p13 1	13 (27%)	35	0.00227 (0.703)	0.517 (1.00)	1 (1.00)	1 (1.00)	0.648 (1.00)	0.509 (1.00)	1 (1.00)	0.613 (1.00)
del 17q24 1	8 (17%)	40	0.236 (1.00)	0.0479 (1.00)	1 (1.00)	0.0437 (1.00)	0.637 (1.00)	0.0289 (1.00)	0.214 (1.00)	0.149 (1.00)
del 19p13 2	4 (8%)	44	1 (1.00)	1 (1.00)	0.484 (1.00)		1 (1.00)	0.427 (1.00)	1 (1.00)	0.663 (1.00)
del 19q13 2	5 (10%)	43	1 (1.00)	0.348 (1.00)	0.484 (1.00)		1 (1.00)	0.66 (1.00)	0.581 (1.00)	0.723 (1.00)
del 22q13 31	7 (15%)	41	0.0967 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.947 (1.00)	0.906 (1.00)	1 (1.00)	0.619 (1.00)
del xq28	3 (6%)	45	0.056 (1.00)	0.234 (1.00)	0.464 (1.00)		0.474 (1.00)	0.441 (1.00)	1 (1.00)

'amp_2p16.1' versus 'METHLYATION_CNMF'

P value = 0.000509 (Fisher's exact test), Q value = 0.16

Table S1. Gene #2: 'amp_2p16.1' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2
ALL	24	24
AMP PEAK 2(2P16.1) MUTATED	2	14
AMP PEAK 2(2P16.1) WILD-TYPE	22	10

Figure S1. Get High-res Image Gene #2: 'amp_2p16.1' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'amp_7p22.3' versus 'CN_CNMF'

P value = 7.62e-05 (Fisher's exact test), Q value = 0.024

Table S2. Gene #6: 'amp_7p22.3' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2
ALL	29	19
AMP PEAK 6(7P22.3) MUTATED	3	13
AMP PEAK 6(7P22.3) WILD-TYPE	26	6

Figure S2. Get High-res Image Gene #6: 'amp_7p22.3' versus Molecular Subtype #1: 'CN_CNMF'

'amp_7q21.3' versus 'CN_CNMF'

P value = 1.04e-05 (Fisher's exact test), Q value = 0.0033

Table S3. Gene #7: 'amp_7q21.3' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2
ALL	29	19
AMP PEAK 7(7Q21.3) MUTATED	2	13
AMP PEAK 7(7Q21.3) WILD-TYPE	27	6

Figure S3. Get High-res Image Gene #7: 'amp_7q21.3' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Molecular subtype file = DLBC-TP.transferedmergedcluster.txt
Number of patients = 48
Number of significantly focal cnvs = 40
Number of molecular subtypes = 8
Exclude genes that fewer than K tumors have alterations, K = 3

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] 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)

[2] 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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