Correlation between mRNA expression and DNA methylation
Prostate Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
Maintained by Richard Park (Boston University/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNA expression and DNA methylation. Broad Institute of MIT and Harvard. doi:10.7908/C19G5KQ1
Overview
Introduction

The role of general epigenetic mechanisms in carcinogenesis and tumor aggressiveness is well documented: CpG island hyper-methylation silences tumor suppressor genes, whereas hypo-methylation promotes the transcriptional activation of oncogenes and induces chromosomal instability. This pipeline calculates and identifies correlations between DNA methylation and gene expression profiles using the available array technologies.

Summary

The top 25 correlated methylation probes per gene are displayed. Total number of matched samples = 419. Number of gene expression samples = 486. Number of methylation samples = 425.

Results
Correlation Histogram

Figure 1.  Histogram of methylation correlation values. n is the number of matched samples between Level 3 CpG site methylation and Level 3 gene expression arrays. Number of Matched Samples = 419

Qvalue Summary Plots

Figure 2.  Plot 1. The estimated pi_0 versus the tuning parameter lambda. Plot 2. The q-values versus the p-values. Plot 3. The number of significant tests versus each q-value cutoff. Plot 4. The number of expected false positives versus the number of significant tests.The first is a plot of the estimate of pi_0 versus its tuning parameter lambda. In most cases, as lambda gets larger, the bias of the estimate decreases, yet the variance increases. Comparing your estimate of pi_0 to this plot allows one to guage its quality. The remaining three plots show how many tests are significant, as well as how many false positives to expect for each q-value cut-off.

Negative Correlation between Methylation and Gene Expression

Table 1.  Get Full Table Top 25 most negatively correlated methylation probes. Correlation Coefficient: See Methods & Data below. Pval and Qval: P- and Q-values of the correlation coefficient. Expression Mean: mean detection level of gene expression probes. Methylation Mean: mean detection level of CpG methylation probes.

Meth_Probe Gene Chrom Position Corr_Coeff Pval Qval Expr_Mean Meth_Mean
cg05165378 ZNF655 7 99155739 -0.91 0 0 8.7 0.42
cg24040502 NLRP2 19 55477810 -0.9 0 0 6.1 0.74
cg22502856 LAMB3 1 209825678 -0.9 0 0 9.1 0.77
cg26104932 CYP27A1 2 219647360 -0.89 0 0 9.4 0.5
cg23531257 DUOX1 15 45422553 -0.89 0 0 7 0.76
cg05253480 IL17RE 3 9944537 -0.88 0 0 7 0.58
cg06797068 DDX43 6 74104600 -0.88 5.9e-131 2.7e-131 3.4 0.71
cg16550453 TDRD1 10 115939018 -0.88 2.6e-137 1.2e-137 6.6 0.67
cg12563839 C14orf159 14 91580507 -0.88 0 0 9 0.34
cg20884605 ALDH2 12 112205368 -0.87 0 0 11 0.41
cg23531257 DUOXA1 15 45422553 -0.87 0 0 4.9 0.76
cg13871633 ZNF662 3 42947385 -0.87 0 0 7 0.43
cg05991820 ECHDC3 10 11785161 -0.87 0 0 7.8 0.52
cg18440523 FAM3B 21 42690652 -0.87 0 0 10 0.6
cg12889195 PAX8 2 113992843 -0.87 0 0 4.7 0.72
cg12889195 LOC654433 2 113992843 -0.86 0 0 5.8 0.72
cg14299940 PHYHD1 9 131684923 -0.86 0 0 8.3 0.41
cg19083407 LOC654433 2 113993142 -0.86 0 0 5.8 0.69
cg12256206 DACT2 6 168719708 -0.86 0 0 8 0.44
cg19083407 PAX8 2 113993142 -0.86 0 0 4.7 0.69
cg09677945 DNAJC15 13 43597657 -0.86 0 0 7.4 0.58
cg23659134 GSTO2 10 106035168 -0.85 0 0 8.1 0.46
cg02216481 ALOX15B 17 7942137 -0.85 0 0 10 0.55
cg00120825 PEX10 1 2338738 -0.85 0 0 11 0.63
cg18404205 SP8 7 20822829 -0.85 0 0 6.4 0.57
cg04860563 TP63 3 189524470 -0.85 0 0 7.9 0.85
Methods & Data
Input

Methylation Array Platforms: Illumina Infinium HumanMethylation27, Illumina Infinium HumanMethylation450, Illumina DNA Methylation OMA002, Illumina DNA Methylation OMA003

  • methylation file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MethylationPreprocess/PRAD-TP/11494025/PRAD-TP.meth.by_min_expr_corr.data.txt

Gene Expression Platforms: Agilent 244K Gene Expression G4502A-07-1, Agilent 244K Gene Expression G4502A-07-2, Agilent 244K Gene Expression G4502A-07-3, Affymetrix Human Exon 1.0 ST Array, Affymetrix HT Human Genome U133 Array

  • gene expression file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/mRNAseq_preprocessor/PRAD-TP/11493681/PRAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

Correlation Coefficient

Level 3 methylation and gene expression arrays were paired on the basis of Entrez Gene ID concordance. The association between CpG site methylation and the level of expression of the corresponding genes was determined by calculating a correlation measure between the two platforms.

  • correlation measure = Spearman

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.