Correlation between mRNA expression and DNA methylation
Esophageal Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1PN94G5
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/C1PN94G5
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 = 125. Number of gene expression samples = 125. Number of methylation samples = 185.

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 = 125

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
cg07773582 LOC440335 16 4845285 -0.87 2e-39 1.1e-38 9.2 0.56
cg07037032 AKR7A3 1 19614429 -0.87 1e-38 5.7e-38 9 0.65
cg09107315 GIPC2 1 78511488 -0.86 6.2e-38 3.5e-37 8.8 0.3
cg06520450 TP63 3 189507396 -0.86 0 0 13 0.56
cg06360527 SOX15 17 7491548 -0.86 6.3e-37 3.5e-36 11 0.49
cg19083407 LOC654433 2 113993142 -0.84 0 0 11 0.59
cg21610815 LOC654433 2 113994035 -0.84 0 0 11 0.56
cg11943056 SLC44A4 6 31845413 -0.84 4.8e-35 2.7e-34 10 0.68
cg11103390 ECHDC3 10 11784920 -0.84 2.1e-34 1.1e-33 9.1 0.55
cg05363903 IQCA1 2 237415899 -0.84 2.6e-34 1.4e-33 8.1 0.56
cg01287476 C2orf65 2 74875548 -0.84 6.6e-34 3.7e-33 6.9 0.53
cg21852589 TMEM139 7 142981689 -0.84 1e-33 5.5e-33 7.2 0.74
cg01883408 CCNI2 5 132083691 -0.83 2.6e-33 1.4e-32 7.9 0.46
cg00231140 ACAA2 18 47339702 -0.83 3.1e-33 1.7e-32 12 0.15
cg01579024 RANBP17 5 170288757 -0.83 8.8e-33 4.8e-32 7.2 0.69
cg15677087 SLC17A9 20 61584850 -0.83 1.9e-32 1e-31 10 0.69
cg01384143 C3orf14 3 62304554 -0.83 2.6e-32 1.4e-31 8.2 0.24
cg25170091 RPH3AL 17 202716 -0.82 4.1e-32 2.2e-31 9.6 0.36
cg12557114 WISP3 6 112375870 -0.82 4e-31 2.2e-30 6.2 0.72
cg11100640 MKRN3 15 23810861 -0.82 1.4e-30 7.2e-30 7.8 0.58
cg04817300 TP53AIP1 11 128812875 -0.82 9.9e-32 5.4e-31 8.1 0.53
cg23292259 MIA2 14 39702965 -0.82 4.4e-23 1.9e-22 5.3 0.79
cg22731359 ZNF256 19 58459136 -0.82 1.4e-31 7.7e-31 7.9 0.23
cg16363586 BST2 19 17516329 -0.82 0 0 13 0.5
cg01404317 SPG20 13 36919819 -0.81 6.7e-31 3.6e-30 12 0.29
cg10878307 PRR15L 17 46034455 -0.81 8.4e-31 4.5e-30 9.6 0.56
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/ESCA-TP/11493594/ESCA-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/ESCA-TP/11493427/ESCA-TP.mRNAseq_RPKM_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.

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