Correlation between APOBEC groups and selected clinical features
Esophageal 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/C11J994T
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 15 clinical features across 185 patients, 3 significant findings detected with Q value < 0.25.

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

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

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between APOBEC groups by 2 different APOBEC scores and 15 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.

Clinical
Features
Statistical
Tests
APOBEC
MUTLOAD
MINESTIMATE
APOBEC
ENRICH
Time to Death logrank test 0.91
(0.957)
0.925
(0.957)
YEARS TO BIRTH Kruskal-Wallis (anova) 0.598
(0.781)
0.0723
(0.31)
PATHOLOGIC STAGE Fisher's exact test 0.0913
(0.342)
0.0687
(0.31)
PATHOLOGY T STAGE Fisher's exact test 0.294
(0.503)
0.159
(0.427)
PATHOLOGY N STAGE Fisher's exact test 0.0172
(0.172)
0.0369
(0.277)
PATHOLOGY M STAGE Fisher's exact test 0.504
(0.709)
1
(1.00)
GENDER Fisher's exact test 0.0521
(0.31)
0.52
(0.709)
RADIATION THERAPY Fisher's exact test 0.152
(0.427)
0.146
(0.427)
KARNOFSKY PERFORMANCE SCORE Kruskal-Wallis (anova) 0.648
(0.793)
0.866
(0.957)
HISTOLOGICAL TYPE Fisher's exact test 1e-05
(0.00015)
1e-05
(0.00015)
NUMBER PACK YEARS SMOKED Kruskal-Wallis (anova) 0.278
(0.503)
0.185
(0.427)
RESIDUAL TUMOR Fisher's exact test 0.66
(0.793)
0.225
(0.481)
NUMBER OF LYMPH NODES Kruskal-Wallis (anova) 0.302
(0.503)
0.751
(0.866)
RACE Fisher's exact test 0.249
(0.498)
0.173
(0.427)
ETHNICITY Fisher's exact test 0.52
(0.709)
0.453
(0.709)
APOBEC group #1: 'APOBEC MUTLOAD MINESTIMATE'

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

Cluster Labels 0 HIGH LOW
Number of samples 145 20 20
'APOBEC MUTLOAD MINESTIMATE' versus 'PATHOLOGY_N_STAGE'

P value = 0.0172 (Fisher's exact test), Q value = 0.17

Table S2.  Clustering Approach #1: 'APOBEC MUTLOAD MINESTIMATE' versus Clinical Feature #5: 'PATHOLOGY_N_STAGE'

nPatients N0 N1 N2 N3
ALL 77 69 12 8
0 53 62 8 6
HIGH 15 3 1 1
LOW 9 4 3 1

Figure S1.  Get High-res Image Clustering Approach #1: 'APOBEC MUTLOAD MINESTIMATE' versus Clinical Feature #5: 'PATHOLOGY_N_STAGE'

'APOBEC MUTLOAD MINESTIMATE' versus 'HISTOLOGICAL_TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.00015

Table S3.  Clustering Approach #1: 'APOBEC MUTLOAD MINESTIMATE' versus Clinical Feature #10: 'HISTOLOGICAL_TYPE'

nPatients ESOPHAGUS ADENOCARCINOMA, NOS ESOPHAGUS SQUAMOUS CELL CARCINOMA
ALL 89 96
0 84 61
HIGH 0 20
LOW 5 15

Figure S2.  Get High-res Image Clustering Approach #1: 'APOBEC MUTLOAD MINESTIMATE' versus Clinical Feature #10: 'HISTOLOGICAL_TYPE'

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 30 10 145
'APOBEC ENRICH' versus 'HISTOLOGICAL_TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.00015

Table S5.  Clustering Approach #2: 'APOBEC ENRICH' versus Clinical Feature #10: 'HISTOLOGICAL_TYPE'

nPatients ESOPHAGUS ADENOCARCINOMA, NOS ESOPHAGUS SQUAMOUS CELL CARCINOMA
ALL 89 96
FC.HIGH.ENRICH 0 30
FC.LOW.ENRICH 5 5
FC.NO.ENRICH 84 61

Figure S3.  Get High-res Image Clustering Approach #2: 'APOBEC ENRICH' versus Clinical Feature #10: 'HISTOLOGICAL_TYPE'

Methods & Data
Input
  • APOBEC groups file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/APOBEC_Pipelines/ESCA-TP/22533622/APOBEC_clinical_corr_input_22539540/APOBEC_for_clinical.correlaion.input.categorical.txt

  • Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/ESCA-TP/22506419/ESCA-TP.merged_data.txt

  • Number of patients = 185

  • Number of selected clinical features = 15

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)