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

Cholangiocarcinoma (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/C1R49PM1

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 7 molecular subtypes across 36 patients, 3 significant findings detected with P value < 0.05 and Q value < 0.25.

del_14q32.12 cnv correlated to 'CN_CNMF'.
del_14q32.11 cnv correlated to 'CN_CNMF'.
del_14q32.33 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 7 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	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
del 14q32 12	20 (56%)	16	0.000242 (0.0389)	0.912 (1.00)	0.0594 (1.00)	0.967 (1.00)	0.757 (1.00)	0.175 (1.00)	0.37 (1.00)
del 14q32 11	20 (56%)	16	0.000242 (0.0389)	0.913 (1.00)	0.0579 (1.00)	0.966 (1.00)	0.754 (1.00)	0.175 (1.00)	0.373 (1.00)
del 14q32 33	20 (56%)	16	0.000242 (0.0389)	0.913 (1.00)	0.0581 (1.00)	0.967 (1.00)	0.757 (1.00)	0.175 (1.00)	0.368 (1.00)
amp 1p22 3	15 (42%)	21	0.736 (1.00)	0.201 (1.00)	0.0714 (1.00)	0.167 (1.00)	0.198 (1.00)	0.736 (1.00)	0.427 (1.00)
amp 1q22	24 (67%)	12	0.302 (1.00)	0.119 (1.00)	0.353 (1.00)	0.926 (1.00)	0.405 (1.00)	1 (1.00)	0.682 (1.00)
amp 11q13 3	8 (22%)	28	1 (1.00)	0.599 (1.00)	0.044 (1.00)	0.298 (1.00)	0.971 (1.00)	0.694 (1.00)	0.853 (1.00)
amp 12q13 2	10 (28%)	26	1 (1.00)	0.806 (1.00)	0.908 (1.00)	0.262 (1.00)	0.52 (1.00)	0.26 (1.00)	0.63 (1.00)
del 1p36 21	30 (83%)	6	0.0203 (1.00)	0.0193 (1.00)	0.00814 (1.00)	0.392 (1.00)	0.128 (1.00)	0.677 (1.00)	0.152 (1.00)
del 3p25 3	28 (78%)	8	0.0438 (1.00)	0.776 (1.00)	0.0699 (1.00)	0.418 (1.00)	0.761 (1.00)	0.424 (1.00)	0.853 (1.00)
del 3p13	28 (78%)	8	0.0438 (1.00)	1 (1.00)	0.288 (1.00)	0.54 (1.00)	0.242 (1.00)	0.694 (1.00)	0.992 (1.00)
del 4q34 3	23 (64%)	13	0.502 (1.00)	0.192 (1.00)	0.329 (1.00)	0.194 (1.00)	0.484 (1.00)	1 (1.00)	0.535 (1.00)
del 5q13 3	8 (22%)	28	0.236 (1.00)	0.0273 (1.00)	0.158 (1.00)	0.856 (1.00)	0.668 (1.00)	0.694 (1.00)	0.569 (1.00)
del 6q13	21 (58%)	15	0.00801 (1.00)	0.274 (1.00)	0.251 (1.00)	0.754 (1.00)	0.344 (1.00)	0.176 (1.00)	0.471 (1.00)
del 6q25 3	25 (69%)	11	0.00338 (0.533)	0.0551 (1.00)	0.0614 (1.00)	0.14 (1.00)	0.183 (1.00)	0.0769 (1.00)	0.0361 (1.00)
del 8p23 1	13 (36%)	23	0.502 (1.00)	0.0759 (1.00)	0.0669 (1.00)	0.612 (1.00)	0.317 (1.00)	0.31 (1.00)	0.242 (1.00)
del 9p21 3	23 (64%)	13	0.502 (1.00)	0.681 (1.00)	0.16 (1.00)	0.173 (1.00)	0.621 (1.00)	0.159 (1.00)	0.734 (1.00)
del 9q21 11	19 (53%)	17	0.525 (1.00)	0.696 (1.00)	0.186 (1.00)	0.32 (1.00)	0.429 (1.00)	0.516 (1.00)	0.518 (1.00)
del 10q26 12	12 (33%)	24	0.732 (1.00)	0.44 (1.00)	0.681 (1.00)	0.471 (1.00)	0.212 (1.00)	0.499 (1.00)	0.225 (1.00)
del 11q25	13 (36%)	23	0.299 (1.00)	0.209 (1.00)	0.639 (1.00)	0.817 (1.00)	0.216 (1.00)	0.484 (1.00)	0.17 (1.00)
del 12q24 13	8 (22%)	28	0.434 (1.00)	0.47 (1.00)	0.615 (1.00)	0.541 (1.00)	0.667 (1.00)	0.424 (1.00)	0.85 (1.00)
del 13q21 32	16 (44%)	20	1 (1.00)	0.832 (1.00)	0.875 (1.00)	0.619 (1.00)	0.488 (1.00)	1 (1.00)	0.288 (1.00)
del 14q22 1	14 (39%)	22	0.0388 (1.00)	1 (1.00)	0.117 (1.00)	0.964 (1.00)	0.972 (1.00)	0.732 (1.00)	0.411 (1.00)
del 16q23 1	7 (19%)	29	0.684 (1.00)	0.663 (1.00)	0.413 (1.00)	0.66 (1.00)	0.0187 (1.00)	1 (1.00)	0.665 (1.00)

'del_14q32.12' versus 'CN_CNMF'

P value = 0.000242 (Fisher's exact test), Q value = 0.039

Table S1. Gene #20: 'del_14q32.12' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2
ALL	19	17
DEL PEAK 16(14Q32.12) MUTATED	5	15
DEL PEAK 16(14Q32.12) WILD-TYPE	14	2

Figure S1. Get High-res Image Gene #20: 'del_14q32.12' versus Molecular Subtype #1: 'CN_CNMF'

'del_14q32.11' versus 'CN_CNMF'

P value = 0.000242 (Fisher's exact test), Q value = 0.039

Table S2. Gene #21: 'del_14q32.11' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2
ALL	19	17
DEL PEAK 17(14Q32.11) MUTATED	5	15
DEL PEAK 17(14Q32.11) WILD-TYPE	14	2

Figure S2. Get High-res Image Gene #21: 'del_14q32.11' versus Molecular Subtype #1: 'CN_CNMF'

'del_14q32.33' versus 'CN_CNMF'

P value = 0.000242 (Fisher's exact test), Q value = 0.039

Table S3. Gene #22: 'del_14q32.33' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2
ALL	19	17
DEL PEAK 18(14Q32.33) MUTATED	5	15
DEL PEAK 18(14Q32.33) WILD-TYPE	14	2

Figure S3. Get High-res Image Gene #22: 'del_14q32.33' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Molecular subtype file = CHOL-TP.transferedmergedcluster.txt
Number of patients = 36
Number of significantly focal cnvs = 23
Number of molecular subtypes = 7
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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