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 2 genes and 8 molecular subtypes across 38 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 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, 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
NFE2L2	6 (16%)	32	0.714 (1.00)	0.503 (1.00)	0.185 (1.00)	0.282 (1.00)	0.128 (1.00)	0.57 (1.00)	0.24 (1.00)	0.103 (1.00)
PIK3CA	9 (24%)	29	0.162 (1.00)	0.439 (1.00)	0.193 (1.00)	0.303 (1.00)	0.797 (1.00)	0.875 (1.00)	0.499 (1.00)	0.255 (1.00)

'NFE2L2 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.714 (Fisher's exact test), Q value = 1

Table S1. Gene #1: 'NFE2L2 MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	14	7	15
NFE2L2 MUTATED	2	2	2
NFE2L2 WILD-TYPE	12	5	13

'NFE2L2 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.503 (Fisher's exact test), Q value = 1

Table S2. Gene #1: 'NFE2L2 MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6
ALL	6	4	12	7	7	2
NFE2L2 MUTATED	0	2	2	1	1	0
NFE2L2 WILD-TYPE	6	2	10	6	6	2

'NFE2L2 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.185 (Fisher's exact test), Q value = 1

Table S3. Gene #1: 'NFE2L2 MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	20	7	10
NFE2L2 MUTATED	4	2	0
NFE2L2 WILD-TYPE	16	5	10

'NFE2L2 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.282 (Fisher's exact test), Q value = 1

Table S4. Gene #1: 'NFE2L2 MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	22	5	3	7
NFE2L2 MUTATED	4	2	0	0
NFE2L2 WILD-TYPE	18	3	3	7

'NFE2L2 MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.128 (Fisher's exact test), Q value = 1

Table S5. Gene #1: 'NFE2L2 MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	13	9	16
NFE2L2 MUTATED	0	2	4
NFE2L2 WILD-TYPE	13	7	12

'NFE2L2 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.57 (Fisher's exact test), Q value = 1

Table S6. Gene #1: 'NFE2L2 MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	6	22	10
NFE2L2 MUTATED	0	5	1
NFE2L2 WILD-TYPE	6	17	9

'NFE2L2 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.24 (Fisher's exact test), Q value = 1

Table S7. Gene #1: 'NFE2L2 MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	11	12	15
NFE2L2 MUTATED	0	2	4
NFE2L2 WILD-TYPE	11	10	11

'NFE2L2 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.103 (Fisher's exact test), Q value = 1

Table S8. Gene #1: 'NFE2L2 MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6	CLUS_7
ALL	2	8	16	6	2	3	1
NFE2L2 MUTATED	0	0	2	2	1	0	1
NFE2L2 WILD-TYPE	2	8	14	4	1	3	0

'PIK3CA MUTATION STATUS' versus 'CN_CNMF'

P value = 0.162 (Fisher's exact test), Q value = 1

Table S9. Gene #2: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	14	7	15
PIK3CA MUTATED	3	0	6
PIK3CA WILD-TYPE	11	7	9

'PIK3CA MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.439 (Fisher's exact test), Q value = 1

Table S10. Gene #2: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6
ALL	6	4	12	7	7	2
PIK3CA MUTATED	1	1	5	0	2	0
PIK3CA WILD-TYPE	5	3	7	7	5	2

'PIK3CA MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.193 (Fisher's exact test), Q value = 1

Table S11. Gene #2: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	20	7	10
PIK3CA MUTATED	7	0	2
PIK3CA WILD-TYPE	13	7	8

'PIK3CA MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.303 (Fisher's exact test), Q value = 1

Table S12. Gene #2: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	22	5	3	7
PIK3CA MUTATED	8	0	0	1
PIK3CA WILD-TYPE	14	5	3	6

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.797 (Fisher's exact test), Q value = 1

Table S13. Gene #2: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	13	9	16
PIK3CA MUTATED	3	3	3
PIK3CA WILD-TYPE	10	6	13

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.875 (Fisher's exact test), Q value = 1

Table S14. Gene #2: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	6	22	10
PIK3CA MUTATED	1	5	3
PIK3CA WILD-TYPE	5	17	7

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.499 (Fisher's exact test), Q value = 1

Table S15. Gene #2: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	11	12	15
PIK3CA MUTATED	3	4	2
PIK3CA WILD-TYPE	8	8	13

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.255 (Fisher's exact test), Q value = 1

Table S16. Gene #2: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6	CLUS_7
ALL	2	8	16	6	2	3	1
PIK3CA MUTATED	0	1	5	0	1	1	1
PIK3CA WILD-TYPE	2	7	11	6	1	2	0

Methods & Data

Input

Mutation data file = transformed.cor.cli.txt
Molecular subtypes file = CESC-TP.transferedmergedcluster.txt
Number of patients = 38
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

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)

Made with Nozzle