Correlation between gene mutation status and selected clinical features

Overview

Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.

Summary

Testing the association between mutation status of 17 genes and 9 clinical features across 247 patients, one significant finding detected with Q value < 0.25.

TP53 mutation correlated to 'HISTOLOGICAL_TYPE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 17 genes and 9 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, one significant finding detected.


		Clinical Features	Time to Death	YEARS TO BIRTH	TUMOR TISSUE SITE	GENDER	RADIATION THERAPY	HISTOLOGICAL TYPE	RESIDUAL TUMOR	RACE	ETHNICITY
	nMutated (%)	nWild-Type	logrank test	Wilcoxon-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	85 (34%)	162	0.748 (1.00)	0.268 (1.00)	0.157 (1.00)	0.592 (1.00)	1 (1.00)	1e-05 (0.00153)	0.739 (1.00)	0.745 (1.00)	0.176 (1.00)
RB1	24 (10%)	223	0.935 (1.00)	0.965 (1.00)	0.914 (1.00)	0.203 (1.00)	0.0959 (1.00)	0.038 (0.831)	0.609 (1.00)	1 (1.00)	1 (1.00)
ATRX	36 (15%)	211	0.226 (1.00)	0.00621 (0.475)	0.874 (1.00)	0.592 (1.00)	0.317 (1.00)	0.226 (1.00)	0.816 (1.00)	0.573 (1.00)	1 (1.00)
NUMBL	8 (3%)	239	0.82 (1.00)	0.0505 (0.966)	0.968 (1.00)	1 (1.00)	0.442 (1.00)	0.468 (1.00)	0.225 (1.00)	1 (1.00)	1 (1.00)
MSH3	7 (3%)	240	0.527 (1.00)	0.637 (1.00)	0.646 (1.00)	0.127 (1.00)	1 (1.00)	0.731 (1.00)	0.88 (1.00)	1 (1.00)	0.131 (1.00)
LTBP3	5 (2%)	242	0.552 (1.00)	0.71 (1.00)	0.37 (1.00)	0.664 (1.00)	0.325 (1.00)	0.676 (1.00)	0.476 (1.00)	0.397 (1.00)	1 (1.00)
EOMES	5 (2%)	242	0.672 (1.00)	0.77 (1.00)	0.114 (1.00)	0.664 (1.00)	0.0274 (0.831)	0.101 (1.00)	1 (1.00)	0.398 (1.00)	1 (1.00)
PTEN	7 (3%)	240	0.673 (1.00)	0.293 (1.00)	0.0201 (0.767)	1 (1.00)	0.364 (1.00)	0.826 (1.00)	0.522 (1.00)	1 (1.00)	1 (1.00)
KRTAP5-5	7 (3%)	240	0.94 (1.00)	0.146 (1.00)	0.703 (1.00)	0.456 (1.00)	0.423 (1.00)	0.385 (1.00)	0.0983 (1.00)	1 (1.00)	0.152 (1.00)
CABLES1	3 (1%)	244	0.536 (1.00)	0.848 (1.00)	0.397 (1.00)	0.597 (1.00)	1 (1.00)	1 (1.00)	0.707 (1.00)	1 (1.00)	1 (1.00)
TRAF7	4 (2%)	243	0.711 (1.00)	0.848 (1.00)	0.416 (1.00)	0.338 (1.00)	1 (1.00)	0.345 (1.00)	0.61 (1.00)	1 (1.00)	1 (1.00)
LOR	6 (2%)	241	0.758 (1.00)	0.848 (1.00)	0.294 (1.00)	0.419 (1.00)	0.673 (1.00)	0.192 (1.00)	0.411 (1.00)	1 (1.00)	1 (1.00)
R3HDM1	4 (2%)	243	0.948 (1.00)	0.207 (1.00)	0.126 (1.00)	1 (1.00)	0.583 (1.00)	0.638 (1.00)	0.478 (1.00)	1 (1.00)	1 (1.00)
NF1	9 (4%)	238	0.517 (1.00)	0.268 (1.00)	0.194 (1.00)	0.736 (1.00)	0.456 (1.00)	0.0372 (0.831)	0.118 (1.00)	1 (1.00)	1 (1.00)
COL4A3	4 (2%)	243	0.14 (1.00)	0.542 (1.00)	0.176 (1.00)	1 (1.00)	0.323 (1.00)	0.17 (1.00)	0.118 (1.00)	1 (1.00)	1 (1.00)
MEGF9	3 (1%)	244	0.225 (1.00)	0.292 (1.00)	0.0143 (0.728)	0.597 (1.00)	1 (1.00)	0.473 (1.00)	0.36 (1.00)	1 (1.00)	1 (1.00)
SCAP	3 (1%)	244	0.505 (1.00)	0.36 (1.00)	0.296 (1.00)	0.0969 (1.00)	0.557 (1.00)	0.894 (1.00)	0.358 (1.00)	1 (1.00)	1 (1.00)

'TP53 MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.0015

Table S1. Gene #1: 'TP53 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients	DEDIFFERENTIATED LIPOSARCOMA	DESMOID TUMOR	GIANT CELL 'MFH' / UNDIFFERENTIATED PLEOMORPHIC SARCOMA WITH GIANT CELLS	LEIOMYOSARCOMA (LMS)	MALIGNANT PERIPHERAL NERVE SHEATH TUMORS (MPNST)	MYXOFIBROSARCOMA	PLEOMORPHIC 'MFH' / UNDIFFERENTIATED PLEOMORPHIC SARCOMA	SARCOMA; SYNOVIAL; POORLY DIFFERENTIATED	SYNOVIAL SARCOMA - BIPHASIC	SYNOVIAL SARCOMA - MONOPHASIC	UNDIFFERENTIATED PLEOMORPHIC SARCOMA (UPS)
ALL	56	2	1	98	8	22	29	2	2	6	21
TP53 MUTATED	5	0	0	50	1	8	12	0	0	0	9
TP53 WILD-TYPE	51	2	1	48	7	14	17	2	2	6	12

Figure S1. Get High-res Image Gene #1: 'TP53 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

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/SARC-TP/22573934/transformed.cor.cli.txt
Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/SARC-TP/22507207/SARC-TP.merged_data.txt
Number of patients = 247
Number of significantly mutated genes = 17
Number of selected clinical features = 9
Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

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] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)

[2] 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)

[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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