Correlation between copy number variation genes (focal events) and molecular subtypes
Mesothelioma (Primary solid tumor)
15 July 2014 | analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1KD1WQ1
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/C1KD1WQ1
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 23 focal events and 8 molecular subtypes across 37 patients, 2 significant findings detected with P value < 0.05 and Q value < 0.25.

- del_3p21.1 cnv correlated to 'MIRSEQ_CNMF'.

- del_9p21.3 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 23 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, 2 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
del 3p21 1 | 21 (57%) | 16 | 0.519 (1.00) | 0.746 (1.00) | 0.315 (1.00) | 0.00807 (1.00) | 0.000723 (0.129) | 0.0582 (1.00) | 0.00172 (0.305) | 0.00618 (1.00)
del 9p21 3 | 23 (62%) | 14 | 2.1e-05 (0.00378) | 1 (1.00) | 0.164 (1.00) | 0.0675 (1.00) | 1 (1.00) | 0.297 (1.00) | 1 (1.00) | 0.458 (1.00)
amp 12p11 21 | 10 (27%) | 27 | 0.00948 (1.00) | 0.46 (1.00) | 0.711 (1.00) | 0.517 (1.00) | 1 (1.00) | 0.574 (1.00) | 0.665 (1.00) | 0.914 (1.00)
amp 17q24 3 | 12 (32%) | 25 | 0.0768 (1.00) | 1 (1.00) | 0.725 (1.00) | 0.373 (1.00) | 1 (1.00) | 0.0665 (1.00) | 0.665 (1.00) | 0.418 (1.00)
amp 19q13 43 | 4 (11%) | 33 | 0.296 (1.00) | 1 (1.00) | 0.603 (1.00) | 0.178 (1.00) | 1 (1.00) | 0.597 (1.00) | 1 (1.00) | 0.412 (1.00)
amp 20p12 1 | 4 (11%) | 33 | 0.618 (1.00) | 1 (1.00) | 1 (1.00) | 1 (1.00) | 1 (1.00) |  | 1 (1.00) |
del 1p36 23 | 17 (46%) | 20 | 0.00298 (0.521) | 1 (1.00) | 1 (1.00) | 0.209 (1.00) | 0.688 (1.00) | 0.0651 (1.00) | 0.695 (1.00) | 0.0203 (1.00)
del 1p22 1 | 17 (46%) | 20 | 0.104 (1.00) | 0.0994 (1.00) | 0.738 (1.00) | 0.916 (1.00) | 1 (1.00) | 0.541 (1.00) | 1 (1.00) | 0.612 (1.00)
del 2q35 | 8 (22%) | 29 | 0.0554 (1.00) | 0.428 (1.00) | 1 (1.00) | 0.879 (1.00) | 1 (1.00) | 0.213 (1.00) | 0.598 (1.00) | 0.163 (1.00)
del 4q26 | 18 (49%) | 19 | 0.00814 (1.00) | 0.103 (1.00) | 0.0184 (1.00) | 0.0471 (1.00) | 1 (1.00) | 0.136 (1.00) | 1 (1.00) | 0.112 (1.00)
del 5q23 2 | 7 (19%) | 30 | 0.202 (1.00) | 0.416 (1.00) | 1 (1.00) | 1 (1.00) | 1 (1.00) | 0.913 (1.00) | 1 (1.00) | 0.541 (1.00)
del 6q22 31 | 20 (54%) | 17 | 0.508 (1.00) | 0.517 (1.00) | 0.315 (1.00) | 0.0996 (1.00) | 1 (1.00) | 0.0983 (1.00) | 1 (1.00) | 0.216 (1.00)
del 10p15 1 | 13 (35%) | 24 | 0.0357 (1.00) | 0.512 (1.00) | 0.164 (1.00) | 0.172 (1.00) | 1 (1.00) | 0.393 (1.00) | 0.692 (1.00) | 0.254 (1.00)
del 10q22 3 | 7 (19%) | 30 | 0.437 (1.00) | 0.68 (1.00) | 0.402 (1.00) | 0.335 (1.00) | 1 (1.00) | 0.756 (1.00) | 0.365 (1.00) | 0.14 (1.00)
del 10q24 1 | 13 (35%) | 24 | 0.489 (1.00) | 0.731 (1.00) | 1 (1.00) | 0.561 (1.00) | 0.228 (1.00) | 0.161 (1.00) | 0.0447 (1.00) | 0.0182 (1.00)
del 13q13 3 | 21 (57%) | 16 | 0.0178 (1.00) | 0.508 (1.00) | 0.176 (1.00) | 0.694 (1.00) | 1 (1.00) | 0.814 (1.00) | 1 (1.00) | 0.575 (1.00)
del 14q11 2 | 16 (43%) | 21 | 0.00896 (1.00) | 0.746 (1.00) | 1 (1.00) | 0.211 (1.00) | 0.105 (1.00) | 0.157 (1.00) | 0.431 (1.00) | 0.0261 (1.00)
del 14q32 31 | 19 (51%) | 18 | 0.00255 (0.449) | 1 (1.00) | 1 (1.00) | 0.127 (1.00) | 0.105 (1.00) | 0.157 (1.00) | 0.431 (1.00) | 0.0255 (1.00)
del 15q15 1 | 14 (38%) | 23 | 0.00157 (0.279) | 1 (1.00) | 0.305 (1.00) | 0.0788 (1.00) | 1 (1.00) | 0.465 (1.00) | 1 (1.00) | 0.25 (1.00)
del 16p13 3 | 3 (8%) | 34 | 1 (1.00) | 0.0875 (1.00) | 0.229 (1.00) | 0.479 (1.00) | 1 (1.00) |  | 1 (1.00) |
del 16q21 | 9 (24%) | 28 | 0.0239 (1.00) | 1 (1.00) | 1 (1.00) | 0.232 (1.00) | 0.664 (1.00) | 0.612 (1.00) | 0.401 (1.00) | 0.518 (1.00)
del 16q24 1 | 11 (30%) | 26 | 0.00342 (0.596) | 0.495 (1.00) | 0.146 (1.00) | 0.752 (1.00) | 1 (1.00) | 0.76 (1.00) | 1 (1.00) | 0.74 (1.00)
del 22q12 2 | 29 (78%) | 8 | 0.104 (1.00) | 0.109 (1.00) | 0.691 (1.00) | 1 (1.00) | 0.0532 (1.00) | 0.134 (1.00) | 0.0171 (1.00) | 0.00744 (1.00)

'del_3p21.1' versus 'MIRSEQ_CNMF'

P value = 0.000723 (Fisher's exact test), Q value = 0.13

Table S1. Gene #8: 'del_3p21.1' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients | CLUS_1 | CLUS_2
--- | --- | ---
ALL | 16 | 10
DEL PEAK 4(3P21.1) MUTATED | 5 | 10
DEL PEAK 4(3P21.1) WILD-TYPE | 11 | 0

Figure S1. Get High-res Image Gene #8: 'del_3p21.1' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

'del_9p21.3' versus 'CN_CNMF'

P value = 2.1e-05 (Fisher's exact test), Q value = 0.0038

Table S2. Gene #12: 'del_9p21.3' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2
--- | --- | ---
ALL | 16 | 21
DEL PEAK 8(9P21.3) MUTATED | 16 | 7
DEL PEAK 8(9P21.3) WILD-TYPE | 0 | 14

Figure S2. Get High-res Image Gene #12: 'del_9p21.3' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data
Input

- Copy number data file = transformed.cor.cli.txt

- Molecular subtype file = MESO-TP.transferedmergedcluster.txt

- Number of patients = 37

- Number of significantly focal cnvs = 23

- 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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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