Correlation between gene mutation status and molecular subtypes
Kidney Chromophobe (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1RX99F5
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/C1RX99F5
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 8 molecular subtypes across 66 patients, one significant finding detected with P value < 0.05 and Q value < 0.25.

- PTEN mutation correlated to 'MIRSEQ_MATURE_CNMF'.

Results
Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 2 genes and 8 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 | CN CNMF | METHLYATION CNMF | 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 | Chi-square test | Fisher's exact test | Fisher's exact test | Chi-square test | Fisher's exact test
PTEN | 6 (9%) | 60 | 0.0988 (1.00) | 0.321 (1.00) | 0.351 (1.00) | 0.13 (1.00) | 0.354 (1.00) | 0.585 (1.00) | 0.00617 (0.0988) | 0.0812 (1.00)
TP53 | 22 (33%) | 44 | 0.615 (1.00) | 0.0882 (1.00) | 0.0646 (0.904) | 0.0593 (0.89) | 0.645 (1.00) | 0.706 (1.00) | 0.76 (1.00) | 0.898 (1.00)

'PTEN MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.00617 (Chi-square test), Q value = 0.099

Table S1. Gene #2: 'PTEN MUTATION STATUS' versus Clinical Feature #7: 'MIRSEQ_MATURE_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5
--- | --- | --- | --- | --- | ---
ALL | 10 | 16 | 16 | 10 | 14
PTEN MUTATED | 4 | 0 | 1 | 0 | 1
PTEN WILD-TYPE | 6 | 16 | 15 | 10 | 13

Figure S1. Get High-res Image Gene #2: 'PTEN MUTATION STATUS' versus Clinical Feature #7: 'MIRSEQ_MATURE_CNMF'

Methods & Data
Input

- Mutation data file = KICH-TP.mutsig.cluster.txt

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

- Number of patients = 66

- Number of significantly mutated genes = 2

- 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

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] 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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