Correlation between mRNA expression and DNA methylation
Pheochromocytoma and Paraganglioma (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/C1ZC81TR
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 = 179. Number of gene expression samples = 179. Number of methylation samples = 179.

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 = 179

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
cg12889195 LOC654433 2 113992843 -0.92 0 0 5.5 0.78
cg12889195 PAX8 2 113992843 -0.89 0 0 4.4 0.78
cg13869600 RET 10 43575142 -0.83 0 0 13 0.58
cg07135629 AQP1 7 30951709 -0.82 0 0 11 0.78
cg14956327 DDO 6 110737053 -0.82 0 0 5.5 0.43
cg11574092 PP14571 2 241394528 -0.81 0 0 4.9 0.5
cg23688479 CCDC152 5 42756851 -0.77 0 0 7.8 0.55
cg12069042 PLXNB1 3 48466700 -0.77 0 0 11 0.46
cg17647091 LOC100240735 12 54474036 -0.77 0 0 4.9 0.36
cg24049451 PNMT 17 37826163 -0.76 0 0 9.8 0.57
cg01861509 SPOCK2 10 73849626 -0.76 0 0 14 0.5
cg21743307 CACNA2D3 3 54159139 -0.76 0 0 10 0.29
cg11578532 TSTD1 1 161008127 -0.76 0 0 8 0.43
cg12450391 FZD4 11 86660015 -0.75 0 0 9.9 0.71
cg24772388 GYPC 2 127414883 -0.74 0 0 8.4 0.58
cg13806741 FAM181B 11 82443436 -0.74 0 0 8.1 0.37
cg06456031 TMEM140 7 134832850 -0.74 0 0 8.3 0.51
cg07157834 PM20D1 1 205819609 -0.74 0 0 4.8 0.56
cg26394940 C22orf26 22 46449461 -0.74 0 0 3.3 0.32
cg16363586 BST2 19 17516329 -0.73 0 0 9.5 0.77
cg18640660 STRA6 15 74495657 -0.73 0 0 10 0.51
cg07436701 MMRN2 10 88717623 -0.73 0 0 10 0.64
cg23501051 LOC100126784 11 19736912 -0.73 0 0 8.1 0.21
cg06197492 H19 11 2016605 -0.73 0 0 12 0.76
cg15660807 ACCN4 2 220381734 -0.73 0 0 9 0.39
cg24122407 IGF1R 15 99232208 -0.73 0 0 11 0.43
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/PCPG-TP/11493883/PCPG-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/PCPG-TP/11493637/PCPG-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.