Correlation between APOBEC groups and selected clinical features
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
Maintained by Hailei Zhang (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between APOBEC groups and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C19C6WZ7
Overview
Introduction

This pipeline computes the correlation between APOBRC groups and selected clinical features.

Summary

Testing the association between APOBEC groups identified by 2 different apobec score and 4 clinical features across 248 patients, 4 significant findings detected with Q value < 0.25.

  • 3 subtypes identified in current cancer cohort by 'APOBEC MUTLOAD MINESTIMATE'. These subtypes correlate to 'HISTOLOGICAL_TYPE' and 'RESIDUAL_TUMOR'.

  • 2 subtypes identified in current cancer cohort by 'APOBEC ENRICH'. These subtypes correlate to 'HISTOLOGICAL_TYPE' and 'RESIDUAL_TUMOR'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between APOBEC groups by 2 different APOBEC scores and 4 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 4 significant findings detected.

Clinical
Features
Statistical
Tests
APOBEC
MUTLOAD
MINESTIMATE
APOBEC
ENRICH
Time to Death logrank test 0.983
(1)
0.992
(1)
RADIATION THERAPY Fisher's exact test 0.891
(1)
1
(1)
HISTOLOGICAL TYPE Fisher's exact test 0.00021
(0.00168)
0.0017
(0.0068)
RESIDUAL TUMOR Fisher's exact test 0.0258
(0.0517)
0.00823
(0.0219)
APOBEC group #1: 'APOBEC MUTLOAD MINESTIMATE'

Table S1.  Description of APOBEC group #1: 'APOBEC MUTLOAD MINESTIMATE'

Cluster Labels 0 HIGH LOW
Number of samples 236 6 6
'APOBEC MUTLOAD MINESTIMATE' versus 'HISTOLOGICAL_TYPE'

P value = 0.00021 (Fisher's exact test), Q value = 0.0017

Table S2.  Clustering Approach #1: 'APOBEC MUTLOAD MINESTIMATE' versus Clinical Feature #3: 'HISTOLOGICAL_TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA MIXED SEROUS AND ENDOMETRIOID SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 200 4 44
0 196 4 36
HIGH 4 0 2
LOW 0 0 6

Figure S1.  Get High-res Image Clustering Approach #1: 'APOBEC MUTLOAD MINESTIMATE' versus Clinical Feature #3: 'HISTOLOGICAL_TYPE'

'APOBEC MUTLOAD MINESTIMATE' versus 'RESIDUAL_TUMOR'

P value = 0.0258 (Fisher's exact test), Q value = 0.052

Table S3.  Clustering Approach #1: 'APOBEC MUTLOAD MINESTIMATE' versus Clinical Feature #4: 'RESIDUAL_TUMOR'

nPatients R0 R1 R2 RX
ALL 172 10 7 18
0 165 10 4 18
HIGH 3 0 2 0
LOW 4 0 1 0

Figure S2.  Get High-res Image Clustering Approach #1: 'APOBEC MUTLOAD MINESTIMATE' versus Clinical Feature #4: 'RESIDUAL_TUMOR'

APOBEC group #2: 'APOBEC ENRICH'

Table S4.  Description of APOBEC group #2: 'APOBEC ENRICH'

Cluster Labels FC.HIGH.ENRICH FC.LOW.ENRICH FC.NO.ENRICH
Number of samples 11 1 236
'APOBEC ENRICH' versus 'HISTOLOGICAL_TYPE'

P value = 0.0017 (Fisher's exact test), Q value = 0.0068

Table S5.  Clustering Approach #2: 'APOBEC ENRICH' versus Clinical Feature #3: 'HISTOLOGICAL_TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA MIXED SEROUS AND ENDOMETRIOID SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 200 4 43
FC.HIGH.ENRICH 4 0 7
FC.NO.ENRICH 196 4 36

Figure S3.  Get High-res Image Clustering Approach #2: 'APOBEC ENRICH' versus Clinical Feature #3: 'HISTOLOGICAL_TYPE'

'APOBEC ENRICH' versus 'RESIDUAL_TUMOR'

P value = 0.00823 (Fisher's exact test), Q value = 0.022

Table S6.  Clustering Approach #2: 'APOBEC ENRICH' versus Clinical Feature #4: 'RESIDUAL_TUMOR'

nPatients R0 R1 R2 RX
ALL 171 10 7 18
FC.HIGH.ENRICH 6 0 3 0
FC.NO.ENRICH 165 10 4 18

Figure S4.  Get High-res Image Clustering Approach #2: 'APOBEC ENRICH' versus Clinical Feature #4: 'RESIDUAL_TUMOR'

Methods & Data
Input
  • APOBEC groups file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/APOBEC_Pipelines/UCEC-TP/22555825/__DELETED__1436046:APOBEC_clinical_corr_input_22572090/APOBEC_for_clinical.correlaion.input.categorical.txt

  • Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/UCEC-TP/22507145/UCEC-TP.merged_data.txt

  • Number of patients = 248

  • Number of selected clinical features = 4

APOBEC classification

APOBEC classification based on APOBEC_MutLoad_MinEstimate : a. APOBEC non group -- samples with zero value, b. APOBEC high group -- samples above median value in non zero samples, c. APOBEC low group -- samples below median value in non zero samples.

APOBEC classification based on APOBEC_enrich : a. No Enrichmment group -- all samples with BH_Fisher_p-value_tCw > 0.05, b. Low enrichment group -- samples with BH_Fisher_p-value_tCw = < 0.05 and APOBEC_enrich=<2, c. High enrichment group -- samples with BH_Fisher_p-value_tCw =< 0.05 and APOBEC_enrich>2.

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 clinical features, 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.

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.

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)