Correlation between copy number variations of arm-level result and molecular subtypes
Pancreatic Adenocarcinoma (Primary solid tumor)
23 May 2013 | analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1833Q3R
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 molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1833Q3R
Overview
Introduction

This pipeline computes the correlation between significant arm-level copy number variations (cnvs) and subtypes.

Summary

Testing the association between copy number variation 19 arm-level results and 8 molecular subtypes across 50 patients, 5 significant findings detected with Q value < 0.25.

- 6q loss cnv correlated to 'METHLYATION_CNMF'.

- 9p loss cnv correlated to 'CN_CNMF'.

- 17p loss cnv correlated to 'CN_CNMF'.

- 18q loss cnv correlated to 'CN_CNMF'.

- 21q loss 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 19 arm-level results and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 5 significant findings detected.

|  | Molecular subtypes | 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 | Chi-square test | Fisher's exact test | Fisher's exact test | Fisher's exact test
6q loss | 0 (0%) | 42 | 0.014 (1.00) | 0.000163 (0.0228) | 0.0212 (1.00) | 0.0341 (1.00) | 0.00374 (0.49) | 0.00756 (0.944) | 0.0211 (1.00) | 0.00756 (0.944)
9p loss | 0 (0%) | 42 | 0.0014 (0.192) | 0.00254 (0.343) | 0.186 (1.00) | 0.0341 (1.00) | 0.0649 (1.00) | 0.119 (1.00) | 0.0211 (1.00) | 0.119 (1.00)
17p loss | 0 (0%) | 40 | 1.83e-05 (0.00258) | 0.00202 (0.275) | 0.412 (1.00) | 0.0101 (1.00) | 0.184 (1.00) | 0.0367 (1.00) | 0.0212 (1.00) | 0.0367 (1.00)
18q loss | 0 (0%) | 43 | 0.000968 (0.135) | 0.00694 (0.882) | 0.664 (1.00) | 0.0341 (1.00) | 0.0461 (1.00) | 0.396 (1.00) | 0.185 (1.00) | 0.396 (1.00)
21q loss | 0 (0%) | 43 | 0.000968 (0.135) | 0.00694 (0.882) | 0.0212 (1.00) | 0.0341 (1.00) | 0.0625 (1.00) | 0.119 (1.00) | 0.0211 (1.00) | 0.119 (1.00)
1q gain | 0 (0%) | 47 | 0.0449 (1.00) | 0.0562 (1.00) | 0.488 (1.00) |  |  |  | 0.488 (1.00) |
8q gain | 0 (0%) | 43 | 0.00605 (0.774) | 0.0405 (1.00) | 0.186 (1.00) | 0.258 (1.00) | 0.219 (1.00) | 0.0305 (1.00) | 0.0946 (1.00) | 0.0305 (1.00)
18p gain | 0 (0%) | 45 | 0.0105 (1.00) | 0.12 (1.00) | 0.233 (1.00) | 0.313 (1.00) | 0.404 (1.00) | 0.0637 (1.00) | 0.108 (1.00) | 0.0637 (1.00)
20q gain | 0 (0%) | 46 | 0.00306 (0.41) | 0.538 (1.00) | 1 (1.00) | 1 (1.00) | 0.353 (1.00) | 0.515 (1.00) | 0.607 (1.00) | 0.515 (1.00)
6p loss | 0 (0%) | 45 | 0.0152 (1.00) | 0.00491 (0.638) | 0.0486 (1.00) | 0.0605 (1.00) | 0.0184 (1.00) | 0.018 (1.00) | 0.0485 (1.00) | 0.018 (1.00)
9q loss | 0 (0%) | 47 | 0.237 (1.00) | 0.0562 (1.00) | 1 (1.00) |  |  |  | 1 (1.00) |
10p loss | 0 (0%) | 47 | 0.0173 (1.00) | 0.0562 (1.00) | 0.488 (1.00) |  | 0.0309 (1.00) | 0.217 (1.00) | 0.233 (1.00) | 0.217 (1.00)
10q loss | 0 (0%) | 47 | 0.0786 (1.00) | 0.0562 (1.00) | 0.488 (1.00) |  | 0.198 (1.00) | 0.217 (1.00) | 0.233 (1.00) | 0.217 (1.00)
12p loss | 0 (0%) | 47 | 0.0449 (1.00) | 0.0562 (1.00) | 0.233 (1.00) | 0.313 (1.00) | 0.198 (1.00) | 0.217 (1.00) | 0.233 (1.00) | 0.217 (1.00)
12q loss | 0 (0%) | 45 | 0.0152 (1.00) | 0.00491 (0.638) | 0.607 (1.00) | 0.184 (1.00) | 0.422 (1.00) | 0.515 (1.00) | 0.108 (1.00) | 0.515 (1.00)
13q loss | 0 (0%) | 47 | 0.0173 (1.00) | 0.341 (1.00) | 0.488 (1.00) |  | 0.0309 (1.00) | 0.217 (1.00) | 0.233 (1.00) | 0.217 (1.00)
17q loss | 0 (0%) | 46 | 0.00306 (0.41) | 0.0168 (1.00) | 1 (1.00) | 0.313 (1.00) | 0.114 (1.00) | 0.515 (1.00) | 0.108 (1.00) | 0.515 (1.00)
18p loss | 0 (0%) | 46 | 0.0318 (1.00) | 0.0168 (1.00) | 1 (1.00) | 0.313 (1.00) | 0.568 (1.00) | 0.79 (1.00) | 1 (1.00) | 0.79 (1.00)
22q loss | 0 (0%) | 46 | 0.00306 (0.41) | 0.12 (1.00) | 0.233 (1.00) | 0.313 (1.00) | 0.198 (1.00) | 0.217 (1.00) | 0.233 (1.00) | 0.217 (1.00)

'6q loss' versus 'METHLYATION_CNMF'

P value = 0.000163 (Fisher's exact test), Q value = 0.023

Table S1. Gene #6: '6q loss' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 18 | 19 | 12
6Q LOSS CNV | 8 | 0 | 0
6Q LOSS WILD-TYPE | 10 | 19 | 12

Figure S1. Get High-res Image Gene #6: '6q loss' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'9p loss' versus 'CN_CNMF'

P value = 0.0014 (Fisher's exact test), Q value = 0.19

Table S2. Gene #7: '9p loss' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 12 | 28 | 10
9P LOSS CNV | 6 | 1 | 1
9P LOSS WILD-TYPE | 6 | 27 | 9

Figure S2. Get High-res Image Gene #7: '9p loss' versus Molecular Subtype #1: 'CN_CNMF'

'17p loss' versus 'CN_CNMF'

P value = 1.83e-05 (Fisher's exact test), Q value = 0.0026

Table S3. Gene #14: '17p loss' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 12 | 28 | 10
17P LOSS CNV | 7 | 0 | 3
17P LOSS WILD-TYPE | 5 | 28 | 7

Figure S3. Get High-res Image Gene #14: '17p loss' versus Molecular Subtype #1: 'CN_CNMF'

'18q loss' versus 'CN_CNMF'

P value = 0.000968 (Fisher's exact test), Q value = 0.13

Table S4. Gene #17: '18q loss' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 12 | 28 | 10
18Q LOSS CNV | 5 | 0 | 2
18Q LOSS WILD-TYPE | 7 | 28 | 8

Figure S4. Get High-res Image Gene #17: '18q loss' versus Molecular Subtype #1: 'CN_CNMF'

'21q loss' versus 'CN_CNMF'

P value = 0.000968 (Fisher's exact test), Q value = 0.13

Table S5. Gene #18: '21q loss' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 12 | 28 | 10
21Q LOSS CNV | 5 | 0 | 2
21Q LOSS WILD-TYPE | 7 | 28 | 8

Figure S5. Get High-res Image Gene #18: '21q loss' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data
Input

- Mutation data file = broad_values_by_arm.mutsig.cluster.txt

- Molecular subtypes file = PAAD-TP.transferedmergedcluster.txt

- Number of patients = 50

- Number of significantly arm-level cnvs = 19

- Number of molecular subtypes = 8

- Exclude genes that fewer than K tumors have mutations, 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

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

- 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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[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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