Correlation between gene mutation status and molecular subtypes
Overview
Introduction

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

Summary

Testing the association between mutation status of 4 genes and 8 molecular subtypes across 66 patients, no significant finding detected with P value < 0.05 and Q value < 0.25.

  • No gene mutations related to molecuar subtypes.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 4 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, no 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 Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
TP53 22 (33%) 44 0.615
(0.841) 		0.089
(0.637) 		0.0652
(0.637) 		0.0153
(0.488) 		0.644
(0.841) 		0.657
(0.841) 		1
(1.00) 		0.692
(0.852)
PTEN 6 (9%) 60 0.0995
(0.637) 		0.321
(0.704) 		0.354
(0.704) 		0.478
(0.823) 		0.355
(0.704) 		0.0676
(0.637) 		0.372
(0.704) 		0.374
(0.704)
PABPC1 7 (11%) 59 0.488
(0.823) 		0.238
(0.704) 		0.206
(0.704) 		0.741
(0.878) 		0.61
(0.841) 		0.31
(0.704) 		0.286
(0.704) 		0.146
(0.693)
URGCP 3 (5%) 63 0.644
(0.841) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.194
(0.704) 		0.541
(0.841) 		0.152
(0.693)
'TP53 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.615 (Fisher's exact test), Q value = 0.84

Table S1.  Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 5 47 14
TP53 MUTATED 2 14 6
TP53 WILD-TYPE 3 33 8
'TP53 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.089 (Fisher's exact test), Q value = 0.64

Table S2.  Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 18 35 13
TP53 MUTATED 3 16 3
TP53 WILD-TYPE 15 19 10
'TP53 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.0652 (Fisher's exact test), Q value = 0.64

Table S3.  Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 19 22 15 10
TP53 MUTATED 6 6 9 1
TP53 WILD-TYPE 13 16 6 9
'TP53 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.0153 (Fisher's exact test), Q value = 0.49

Table S4.  Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7
ALL 19 16 7 6 10 4 4
TP53 MUTATED 5 6 1 0 7 3 0
TP53 WILD-TYPE 14 10 6 6 3 1 4

Figure S1.  Get High-res Image Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'TP53 MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.644 (Fisher's exact test), Q value = 0.84

Table S5.  Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 24 22
TP53 MUTATED 5 9 8
TP53 WILD-TYPE 15 15 14
'TP53 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.657 (Fisher's exact test), Q value = 0.84

Table S6.  Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7
ALL 18 11 12 6 5 5 9
TP53 MUTATED 7 5 3 1 1 3 2
TP53 WILD-TYPE 11 6 9 5 4 2 7
'TP53 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 1 (Fisher's exact test), Q value = 1

Table S7.  Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients CLUS_1 CLUS_2
ALL 19 29
TP53 MUTATED 7 11
TP53 WILD-TYPE 12 18
'TP53 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.692 (Fisher's exact test), Q value = 0.85

Table S8.  Gene #1: 'TP53 MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 10 6 5 8 4 6 5 4
TP53 MUTATED 4 3 2 2 1 3 3 0
TP53 WILD-TYPE 6 3 3 6 3 3 2 4
'PTEN MUTATION STATUS' versus 'CN_CNMF'

P value = 0.0995 (Fisher's exact test), Q value = 0.64

Table S9.  Gene #2: 'PTEN MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 5 47 14
PTEN MUTATED 2 3 1
PTEN WILD-TYPE 3 44 13
'PTEN MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.321 (Fisher's exact test), Q value = 0.7

Table S10.  Gene #2: 'PTEN MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 18 35 13
PTEN MUTATED 3 3 0
PTEN WILD-TYPE 15 32 13
'PTEN MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.354 (Fisher's exact test), Q value = 0.7

Table S11.  Gene #2: 'PTEN MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 19 22 15 10
PTEN MUTATED 2 1 3 0
PTEN WILD-TYPE 17 21 12 10
'PTEN MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.478 (Fisher's exact test), Q value = 0.82

Table S12.  Gene #2: 'PTEN MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7
ALL 19 16 7 6 10 4 4
PTEN MUTATED 2 1 0 0 3 0 0
PTEN WILD-TYPE 17 15 7 6 7 4 4
'PTEN MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.355 (Fisher's exact test), Q value = 0.7

Table S13.  Gene #2: 'PTEN MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 24 22
PTEN MUTATED 1 4 1
PTEN WILD-TYPE 19 20 21
'PTEN MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.0676 (Fisher's exact test), Q value = 0.64

Table S14.  Gene #2: 'PTEN MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7
ALL 18 11 12 6 5 5 9
PTEN MUTATED 5 0 0 0 0 1 0
PTEN WILD-TYPE 13 11 12 6 5 4 9
'PTEN MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.372 (Fisher's exact test), Q value = 0.7

Table S15.  Gene #2: 'PTEN MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients CLUS_1 CLUS_2
ALL 19 29
PTEN MUTATED 3 2
PTEN WILD-TYPE 16 27
'PTEN MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.374 (Fisher's exact test), Q value = 0.7

Table S16.  Gene #2: 'PTEN MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 10 6 5 8 4 6 5 4
PTEN MUTATED 3 0 1 0 0 0 1 0
PTEN WILD-TYPE 7 6 4 8 4 6 4 4
'PABPC1 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.488 (Fisher's exact test), Q value = 0.82

Table S17.  Gene #3: 'PABPC1 MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 5 47 14
PABPC1 MUTATED 1 4 2
PABPC1 WILD-TYPE 4 43 12
'PABPC1 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.238 (Fisher's exact test), Q value = 0.7

Table S18.  Gene #3: 'PABPC1 MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 18 35 13
PABPC1 MUTATED 2 2 3
PABPC1 WILD-TYPE 16 33 10
'PABPC1 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.206 (Fisher's exact test), Q value = 0.7

Table S19.  Gene #3: 'PABPC1 MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 19 22 15 10
PABPC1 MUTATED 2 1 1 3
PABPC1 WILD-TYPE 17 21 14 7
'PABPC1 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.741 (Fisher's exact test), Q value = 0.88

Table S20.  Gene #3: 'PABPC1 MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7
ALL 19 16 7 6 10 4 4
PABPC1 MUTATED 2 1 2 1 1 0 0
PABPC1 WILD-TYPE 17 15 5 5 9 4 4
'PABPC1 MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.61 (Fisher's exact test), Q value = 0.84

Table S21.  Gene #3: 'PABPC1 MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 24 22
PABPC1 MUTATED 3 3 1
PABPC1 WILD-TYPE 17 21 21
'PABPC1 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.31 (Fisher's exact test), Q value = 0.7

Table S22.  Gene #3: 'PABPC1 MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7
ALL 18 11 12 6 5 5 9
PABPC1 MUTATED 2 1 0 1 0 0 3
PABPC1 WILD-TYPE 16 10 12 5 5 5 6
'PABPC1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.286 (Fisher's exact test), Q value = 0.7

Table S23.  Gene #3: 'PABPC1 MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients CLUS_1 CLUS_2
ALL 19 29
PABPC1 MUTATED 3 1
PABPC1 WILD-TYPE 16 28
'PABPC1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.146 (Fisher's exact test), Q value = 0.69

Table S24.  Gene #3: 'PABPC1 MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7 CLUS_8
ALL 10 6 5 8 4 6 5 4
PABPC1 MUTATED 0 0 1 0 0 2 1 0
PABPC1 WILD-TYPE 10 6 4 8 4 4 4 4
'URGCP MUTATION STATUS' versus 'CN_CNMF'

P value = 0.644 (Fisher's exact test), Q value = 0.84

Table S25.  Gene #4: 'URGCP MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 5 47 14
URGCP MUTATED 0 2 1
URGCP WILD-TYPE 5 45 13
'URGCP MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 1 (Fisher's exact test), Q value = 1

Table S26.  Gene #4: 'URGCP MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 18 35 13
URGCP MUTATED 1 2 0
URGCP WILD-TYPE 17 33 13
'URGCP MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 1 (Fisher's exact test), Q value = 1

Table S27.  Gene #4: 'URGCP MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 19 22 15 10
URGCP MUTATED 1 1 1 0
URGCP WILD-TYPE 18 21 14 10
'URGCP MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1 (Fisher's exact test), Q value = 1

Table S28.  Gene #4: 'URGCP MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7
ALL 19 16 7 6 10 4 4
URGCP MUTATED 1 1 0 0 1 0 0
URGCP WILD-TYPE 18 15 7 6 9 4 4
'URGCP MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.194 (Fisher's exact test), Q value = 0.7

Table S29.  Gene #4: 'URGCP MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 24 22
URGCP MUTATED 2 0 1
URGCP WILD-TYPE 18 24 21
'URGCP MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.541 (Fisher's exact test), Q value = 0.84

Table S30.  Gene #4: 'URGCP MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6 CLUS_7
ALL 18 11 12 6 5 5 9
URGCP MUTATED 1 0 0 1 0 0 1
URGCP WILD-TYPE 17 11 12 5 5 5 8
'URGCP MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.152 (Fisher's exact test), Q value = 0.69

Table S31.  Gene #4: 'URGCP MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients CLUS_1 CLUS_2
ALL 19 29
URGCP MUTATED 2 0
URGCP WILD-TYPE 17 29
Methods & Data
Input

  • Mutation data file = sample_sig_gene_table.txt from Mutsig_2CV pipeline

  • Processed Mutation data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/KICH-TP/15174159/transformed.cor.cli.txt

  • Molecular subtypes file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_mergedClustering/KICH-TP/15095894/KICH-TP.transferedmergedcluster.txt

  • Number of patients = 66

  • Number of significantly mutated genes = 4

  • 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

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.

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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