Correlation between gene mutation status and molecular subtypes

Thyroid Adenocarcinoma (Mut_RAS)

01 July 2013 | awg_thca__2013_07_01

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 gene mutation status and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1NS0S0D

Overview

Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and molecular subtypes.

Summary

Testing the association between mutation status of 2 genes and 9 molecular subtypes across 51 patients, one significant finding detected with P value < 0.05 and Q value < 0.25.

HRAS mutation correlated to 'METHLYATION_CNMF'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 2 genes and 9 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, one significant finding detected.


		Clinical Features	METHLYATION CNMF	RPPA CNMF	RPPA CHIERARCHICAL	MRNASEQ CNMF	MRNASEQ CHIERARCHICAL	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL	MIRSEQ MATURE CNMF	MIRSEQ MATURE CHIERARCHICAL
	nMutated (%)	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	Chi-square test
HRAS	14 (27%)	37	0.0132 (0.237)	0.0894 (1.00)	0.248 (1.00)	0.0453 (0.771)	0.22 (1.00)	0.366 (1.00)	0.466 (1.00)	0.86 (1.00)	0.264 (1.00)
NRAS	34 (67%)	17	0.217 (1.00)	0.0497 (0.795)	0.267 (1.00)	0.41 (1.00)	0.144 (1.00)	0.93 (1.00)	0.656 (1.00)	0.654 (1.00)	0.154 (1.00)

'HRAS MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.0132 (Fisher's exact test), Q value = 0.24

Table S1. Gene #2: 'HRAS MUTATION STATUS' versus Clinical Feature #1: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	16	27	8
HRAS MUTATED	2	12	0
HRAS WILD-TYPE	14	15	8

Figure S1. Get High-res Image Gene #2: 'HRAS MUTATION STATUS' versus Clinical Feature #1: 'METHLYATION_CNMF'

Methods & Data

Input

Mutation data file = THCA-Mut_RAS.mutsig.cluster.txt
Molecular subtypes file = THCA-Mut_RAS.transferedmergedcluster.txt
Number of patients = 51
Number of significantly mutated genes = 2
Number of Molecular subtypes = 9
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.

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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