Correlation between mRNA expression and DNA methylation
Head and Neck Squamous Cell Carcinoma (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/C1CV4GMG
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 = 497. Number of gene expression samples = 497. Number of methylation samples = 528.

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 = 497

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 -0.87 9.8e-151 6.9e-151 7.4 0.67
cg03669949 DDX43 6 74104426 -0.85 0 0 2.8 0.82
cg12258179 RASIP1 19 49232187 -0.84 0 0 8.5 0.64
cg07590529 TBX18 6 85471973 -0.82 0 0 6 0.55
cg12889195 PAX8 2 113992843 -0.82 0 0 6 0.67
cg00292135 C7orf13 7 156433068 -0.81 0 0 5.9 0.28
cg05396212 KRT19 17 39683705 -0.81 0 0 11 0.39
cg24040502 NLRP2 19 55477810 -0.81 2e-115 1.4e-115 6.4 0.71
cg05991820 ECHDC3 10 11785161 -0.81 0 0 6.3 0.58
cg01328500 IQCG 3 197639792 -0.79 0 0 8.4 0.61
cg01070987 PFN2 3 149687002 -0.79 0 0 11 0.51
cg14732998 ZNF793 19 37997831 -0.78 8.1e-104 5.7e-104 4.3 0.31
cg12557114 WISP3 6 112375870 -0.78 0 0 4 0.74
cg02091185 RANBP17 5 170288766 -0.78 2.8e-100 1.9e-100 3.1 0.67
cg04449108 UGT1A6 2 234601254 -0.78 0 0 7.3 0.82
cg02423817 PTPRCAP 11 67203661 -0.78 0 0 7.4 0.7
cg14299940 PHYHD1 9 131684923 -0.78 0 0 5.9 0.38
cg25451874 ZNF569 19 37958444 -0.78 2.8e-101 2e-101 5.2 0.25
cg23659134 GSTO2 10 106035168 -0.78 0 0 6.8 0.56
cg05806717 TBX6 16 30102542 -0.77 0 0 6 0.72
cg18233746 MGST1 12 16500403 -0.77 0 0 7.2 0.47
cg26314750 C15orf56 15 40545794 -0.77 1.9e-81 1.3e-81 1.7 0.52
cg06384763 ZNF788 19 12203198 -0.77 0 0 4.7 0.39
cg12950007 ZNF528 19 52900970 -0.77 0 0 6 0.27
cg26155983 GPX2 14 65410145 -0.76 0 0 9.7 0.68
cg02768694 C2orf65 2 74875536 -0.76 1.5e-90 1e-90 3 0.54
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/HNSC-TP/11494058/HNSC-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/HNSC-TP/11493471/HNSC-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.