Correlation between mRNA expression and DNA methylation
Pan-kidney cohort (KICH+KIRC+KIRP) (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/C1Q23ZM2
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 = 658. Number of gene expression samples = 889. Number of methylation samples = 660.

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 = 658

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
cg07484727 TMEM204 16 1587309 -0.89 0 0 8.3 0.74
cg22621686 GJA4 1 35260256 -0.89 0 0 8.4 0.8
cg18102633 PLVAP 19 17487776 -0.88 0 0 12 0.81
cg09298971 SLC44A4 6 31846249 -0.88 0 0 8.8 0.67
cg10635645 APOLD1 12 12938397 -0.86 6.3e-191 1e-191 10 0.84
cg08686960 COX7A1 19 36642720 -0.85 0 0 7.5 0.69
cg21550016 LOC654433 2 113992930 -0.85 0 0 4.7 0.86
cg04173992 PDGFRB 5 149520651 -0.85 0 0 11 0.76
cg05490233 PLXND1 3 129321847 -0.84 0 0 11 0.79
cg01443318 HSD11B2 16 67466260 -0.84 0 0 8.6 0.53
cg08450017 CXCR6 3 45984838 -0.84 0 0 5.9 0.82
cg10096378 FAM83F 22 40391617 -0.83 2.2e-148 3.6e-149 4.4 0.58
cg08607625 NOS3 7 150690699 -0.83 0 0 7.8 0.77
cg08207707 ESAM 11 124630919 -0.83 0 0 10 0.78
cg25373579 VEGFA 6 43752302 -0.83 0 0 13 0.63
cg14209037 DLL4 15 41228521 -0.83 0 0 8.9 0.91
cg22245858 SCNN1A 12 6486709 -0.83 0 0 10 0.62
cg00259834 RFTN1 3 16553499 -0.83 0 0 9.2 0.42
cg12712747 COL4A1 13 110900663 -0.83 0 0 13 0.89
cg12090003 BST2 19 17516282 -0.82 0 0 10 0.43
cg12559925 SH3BP4 2 235863365 -0.82 0 0 10 0.61
cg15449664 THY1 11 119294408 -0.82 0 0 11 0.82
cg14326991 GPR116 6 46889760 -0.82 0 0 10 0.78
cg12608132 EPAS1 2 46564242 -0.82 0 0 13 0.83
cg19466563 SPARCL1 4 88450506 -0.82 0 0 12 0.71
cg15397593 CACNA1C 12 2273119 -0.82 0 0 6.6 0.81
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/KIPAN-TP/22318479/KIPAN-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/KIPAN-TP/22311286/KIPAN-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.