Correlation between mRNA expression and DNA methylation
Esophageal Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
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/C13B5XW5
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 = 70. Number of gene expression samples = 70. 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 = 70

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
cg11039314 AGR3 7 16921699 -0.9 2.7e-25 2.4e-24 7.1 0.69
cg06360527 SOX15 17 7491548 -0.88 4.8e-24 4.3e-23 11 0.49
cg05363903 IQCA1 2 237415899 -0.88 3.6e-23 3.1e-22 8.4 0.56
cg15677087 SLC17A9 20 61584850 -0.87 3.3e-22 2.9e-21 11 0.7
cg11103390 ECHDC3 10 11784920 -0.87 3.6e-22 3.2e-21 9.2 0.54
cg19766489 GIPC2 1 78511344 -0.86 5.4e-22 4.7e-21 9.2 0.52
cg01579024 RANBP17 5 170288757 -0.86 8.5e-22 7.4e-21 7.3 0.7
cg01287476 C2orf65 2 74875548 -0.85 5.5e-21 4.7e-20 7.1 0.52
cg07773582 LOC440335 16 4845285 -0.85 7e-21 6e-20 9.1 0.57
cg19511994 MIA2 14 39702922 -0.85 3.9e-16 3e-15 5.3 0.79
cg25984671 TCF15 20 591083 -0.85 3e-20 2.6e-19 5.7 0.36
cg14121234 C10orf108 10 696332 -0.84 4.5e-20 3.9e-19 7.4 0.76
cg07037032 AKR7A3 1 19614429 -0.84 1.1e-19 9.1e-19 8.9 0.66
cg06537230 DLX5 7 96653183 -0.84 1.3e-19 1.1e-18 8.7 0.25
cg11595155 ZNF570 19 37960414 -0.84 2.2e-19 1.8e-18 7.7 0.25
cg21610815 LOC654433 2 113994035 -0.84 0 0 11 0.58
cg23591595 CCDC144B 17 18528638 -0.83 3.1e-19 2.7e-18 7.2 0.75
cg21852589 TMEM139 7 142981689 -0.83 3.3e-19 2.8e-18 7.3 0.75
cg19566405 SLFN12 17 33759965 -0.83 3.6e-19 3e-18 9.1 0.4
cg18432895 DUSP4 8 29205555 -0.83 0 0 12 0.42
cg06520450 TP63 3 189507396 -0.83 0 0 14 0.56
cg02643667 TFF1 21 43786699 -0.83 8.8e-16 6.6e-15 7.7 0.73
cg26475649 C16orf62 16 19567354 -0.83 8.8e-19 7.3e-18 12 0.42
cg12889195 LOC654433 2 113992843 -0.83 0 0 11 0.66
cg04817300 TP53AIP1 11 128812875 -0.83 1.3e-18 1.1e-17 8.3 0.53
cg27352765 DCBLD2 3 98620662 -0.83 0 0 12 0.22
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/9831002/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/9829855/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.