Correlation between copy number variation genes and molecular subtypes

Kidney Chromophobe (Primary solid tumor)

23 May 2013 | analyses__2013_05_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 variation genes and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1MW2F6F

Overview

Introduction

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

Summary

Testing the association between copy number variation of 2 peak regions and 8 molecular subtypes across 66 patients, 4 significant findings detected with Q value < 0.25.

Amp Peak 1(8q11.23) cnvs correlated to 'MRNASEQ_CNMF' and 'MRNASEQ_CHIERARCHICAL'.
Amp Peak 2(15q22.31) cnvs correlated to 'MRNASEQ_CNMF' and 'MRNASEQ_CHIERARCHICAL'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 2 regions and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 4 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	Chi-square test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Chi-square test
Amp Peak 1(8q11 23)	0 (0%)	48	0.165 (1.00)	0.377 (1.00)	0.00906 (0.127)	0.0143 (0.186)	0.942 (1.00)	1 (1.00)	0.73 (1.00)	0.753 (1.00)
Amp Peak 2(15q22 31)	0 (0%)	44	0.147 (1.00)	0.732 (1.00)	0.00546 (0.0873)	0.00823 (0.124)	0.645 (1.00)	0.253 (1.00)	0.845 (1.00)	0.47 (1.00)

'Amp Peak 1(8q11.23)' versus 'MRNASEQ_CNMF'

P value = 0.00906 (Fisher's exact test), Q value = 0.13

Table S1. Gene #1: 'Amp Peak 1(8q11.23)' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	19	22	15	10
AMP PEAK 1(8Q11.23) CNV	3	12	2	1
AMP PEAK 1(8Q11.23) WILD-TYPE	16	10	13	9

Figure S1. Get High-res Image Gene #1: 'Amp Peak 1(8q11.23)' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'Amp Peak 1(8q11.23)' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.0143 (Chi-square test), Q value = 0.19

Table S2. Gene #1: 'Amp Peak 1(8q11.23)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	10	10	17	6	23
AMP PEAK 1(8Q11.23) CNV	2	2	10	0	4
AMP PEAK 1(8Q11.23) WILD-TYPE	8	8	7	6	19

Figure S2. Get High-res Image Gene #1: 'Amp Peak 1(8q11.23)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'Amp Peak 2(15q22.31)' versus 'MRNASEQ_CNMF'

P value = 0.00546 (Fisher's exact test), Q value = 0.087

Table S3. Gene #2: 'Amp Peak 2(15q22.31)' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	19	22	15	10
AMP PEAK 2(15Q22.31) CNV	5	13	4	0
AMP PEAK 2(15Q22.31) WILD-TYPE	14	9	11	10

Figure S3. Get High-res Image Gene #2: 'Amp Peak 2(15q22.31)' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'Amp Peak 2(15q22.31)' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.00823 (Chi-square test), Q value = 0.12

Table S4. Gene #2: 'Amp Peak 2(15q22.31)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	10	10	17	6	23
AMP PEAK 2(15Q22.31) CNV	4	1	11	0	6
AMP PEAK 2(15Q22.31) WILD-TYPE	6	9	6	6	17

Figure S4. Get High-res Image Gene #2: 'Amp Peak 2(15q22.31)' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

Methods & Data

Input

Copy number data file = All Lesions File (all_lesions.conf_##.txt, where ## is the confidence level). The all lesions file is from GISTIC pipeline and summarizes the results from the GISTIC run. It contains data about the significant regions of amplification and deletion as well as which samples are amplified or deleted in each of these regions. The identified regions are listed down the first column, and the samples are listed across the first row, starting in column 10.
Molecular subtype file = KICH-TP.transferedmergedcluster.txt
Number of patients = 66
Number of copy number variation regions = 2
Number of molecular subtypes = 8
Exclude regions 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

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.

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)

[4] GISTIC_version2

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