Correlation between mRNA expression and DNA methylation
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/C1833RCR
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 = 184. Number of gene expression samples = 184. 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 = 184

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 -0.87 0 0 8 0.69
cg07037032 AKR7A3 1 19614429 -0.86 0 0 6 0.6
cg18454133 EFS 14 23835870 -0.86 0 0 8.2 0.65
cg11100640 MKRN3 15 23810861 -0.85 0 0 5.1 0.6
cg01579024 RANBP17 5 170288757 -0.85 0 0 4.3 0.65
cg20034617 C9orf167 9 140172277 -0.85 0 0 9.9 0.27
cg13798146 HDGFRP3 15 83875703 -0.84 0 0 8.6 0.28
cg19249749 CAPN8 1 223853145 -0.84 0 0 5.3 0.75
cg11103390 ECHDC3 10 11784920 -0.84 0 0 6.1 0.56
cg20075683 CCNI2 5 132083910 -0.84 0 0 4.9 0.65
cg16243756 TUSC3 8 15397637 -0.84 0 0 8.1 0.32
cg19766489 GIPC2 1 78511344 -0.84 0 0 6.3 0.48
cg07841477 ERN2 16 23724901 -0.83 0 0 6.2 0.51
cg13159929 SOX15 17 7493222 -0.83 0 0 7.8 0.73
cg24580782 NR0B2 1 27240365 -0.83 4.5e-41 3.3e-41 3.6 0.73
cg20691436 CALML3 10 5567478 -0.83 0 0 8.9 0.61
cg19957162 FZD5 2 208631259 -0.83 0 0 9.8 0.41
cg00214171 LOC100130933 17 73642991 -0.83 0 0 3.3 0.58
cg10878307 PRR15L 17 46034455 -0.83 0 0 7.4 0.53
cg19419519 LGALS4 19 39303698 -0.83 0 0 7.5 0.58
cg17222452 MLF1 3 158289160 -0.83 0 0 7.4 0.26
cg15677087 SLC17A9 20 61584850 -0.83 0 0 7.9 0.65
cg05673892 VILL 3 38033934 -0.82 0 0 7.8 0.66
cg04218124 VIL1 2 219284345 -0.82 0 0 6.3 0.52
cg16785938 SLC2A9 4 10022984 -0.82 0 0 6.8 0.57
cg22731359 ZNF256 19 58459136 -0.82 0 0 5.3 0.25
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/22312696/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/22311243/ESCA-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.