Correlation between mRNA expression and DNA methylation
Stomach and Esophageal carcinoma (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/C1QF8SCJ
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 = 556. Number of gene expression samples = 599. Number of methylation samples = 580.

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 = 556

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
cg09298971 SLC44A4 6 31846249 -0.86 0 0 10 0.61
cg21171625 DNALI1 1 38022607 -0.85 0 0 6.4 0.47
cg18454133 EFS 14 23835870 -0.85 0 0 7.1 0.81
cg01070987 PFN2 3 149687002 -0.84 0 0 9.9 0.56
cg11103390 ECHDC3 10 11784920 -0.84 0 0 5.9 0.58
cg17222452 MLF1 3 158289160 -0.83 0 0 6.5 0.32
cg03669949 DDX43 6 74104426 -0.82 0 0 3.2 0.8
cg12038710 CDH17 8 95220583 -0.82 0 0 9.2 0.69
cg26475649 C16orf62 16 19567354 -0.82 0 0 8.9 0.41
cg01579024 RANBP17 5 170288757 -0.81 5.7e-132 1.1e-132 4.9 0.61
cg27084026 CHFR 12 133464496 -0.81 0 0 8.3 0.2
cg04511125 THNSL2 2 88470314 -0.81 5.5e-130 1.1e-130 6.7 0.37
cg22328208 TSPYL5 8 98289745 -0.81 7.7e-130 1.5e-130 7.3 0.75
cg07280731 PRSS21 16 2867773 -0.81 0 0 5 0.67
cg14059257 KRT7 12 52628105 -0.81 0 0 9.7 0.53
cg25732104 GJB5 1 35220710 -0.81 0 0 5.4 0.55
cg23484087 ZNF256 19 58459097 -0.81 0 0 5.3 0.34
cg18795809 ZNF518B 4 10458531 -0.81 0 0 7.5 0.39
cg02768694 C2orf65 2 74875536 -0.8 2.9e-125 5.8e-126 4.3 0.51
cg02423817 PTPRCAP 11 67203661 -0.8 0 0 7.6 0.7
cg10729426 ZNF549 19 58038585 -0.8 1.2e-124 2.4e-125 6.2 0.42
cg05564251 SP140 2 231090640 -0.8 0 0 6.1 0.71
cg16204205 GATA6 18 19753432 -0.8 0 0 10 0.52
cg19249749 CAPN8 1 223853145 -0.8 0 0 7.3 0.67
cg06907626 NPC1L1 7 44580809 -0.79 0 0 6.1 0.7
cg12557114 WISP3 6 112375870 -0.79 0 0 3.6 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/STES-TP/22318457/STES-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/STES-TP/22315379/STES-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.