Correlation between mRNA expression and DNA methylation
Mesothelioma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
Maintained by Richard Park (Boston University/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between mRNA expression and DNA methylation. Broad Institute of MIT and Harvard. doi:10.7908/C1862FVZ
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 = 87. Number of gene expression samples = 87. Number of methylation samples = 87.

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 = 87

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
cg24040502 NLRP2 19 55477810 -0.89 0 0 5.5 0.72
cg21482265 LOC654433 2 113992762 -0.88 0 0 8.9 0.63
cg24506221 GSTM1 1 110230401 -0.86 0 0 4.9 0.38
cg10178203 CMBL 5 10308250 -0.85 0 0 8.3 0.3
cg12889195 PAX8 2 113992843 -0.85 0 0 6.4 0.65
cg03289872 ZNF667 19 56989102 -0.83 0 0 4.8 0.29
cg12090003 BST2 19 17516282 -0.83 0 0 12 0.33
cg08314660 PKP3 11 394199 -0.82 0 0 5.8 0.69
cg25330387 CLDN1 3 190039141 -0.82 0 0 10 0.63
cg24323726 ZBED2 3 111314186 -0.81 0 0 6.4 0.52
cg21171625 DNALI1 1 38022607 -0.81 0 0 7.2 0.4
cg17078393 LCK 1 32717002 -0.81 0 0 7.1 0.82
cg23696550 TGM1 14 24732386 -0.81 0 0 11 0.6
cg16408081 PTPRCAP 11 67205869 -0.8 0 0 7.9 0.68
cg23167351 KIAA1949 6 30650737 -0.8 0 0 11 0.24
cg16209444 ACOX2 3 58522771 -0.8 0 0 7 0.47
cg09886641 SPESP1 15 69223018 -0.8 0 0 3.7 0.66
cg15790214 HCG11 6 26522325 -0.8 0 0 7.7 0.43
cg06797068 DDX43 6 74104600 -0.79 0 0 2.5 0.77
cg18581405 S1PR4 19 3180035 -0.79 0 0 5.6 0.53
cg05253480 IL17RE 3 9944537 -0.79 0 0 7.3 0.54
cg07786657 CD247 1 167487633 -0.79 0 0 6.6 0.79
cg08989441 TMEM220 17 10633067 -0.79 0 0 6.2 0.09
cg19924352 FAM83A 8 124195402 -0.79 0 0 8 0.56
cg05462570 NAALADL1 11 64814948 -0.78 0 0 6.6 0.26
cg05564251 SP140 2 231090640 -0.78 0 0 6.5 0.73
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/MESO-TP/22318496/MESO-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/MESO-TP/22315366/MESO-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.