Correlation between mRNA expression and DNA methylation
Kidney Chromophobe (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/C11Z434K
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 = 66. Number of gene expression samples = 66. Number of methylation samples = 66.

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 = 66

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
cg07164639 DDO 6 110736958 -0.87 0 0 5.4 0.43
cg07135629 AQP1 7 30951709 -0.85 0 0 11 0.85
cg00903584 PTPN7 1 202128682 -0.84 0 0 4.8 0.85
cg17771150 LCP1 13 46756209 -0.84 0 0 8.6 0.82
cg13101072 FAM50B 6 3849818 -0.84 0 0 6.8 0.46
cg24942416 VSIG2 11 124621829 -0.84 0 0 6.2 0.68
cg06099459 C12orf77 12 25150530 -0.83 0 0 3.4 0.76
cg19774846 RUNX3 1 25292225 -0.83 0 0 6.2 0.92
cg08686960 COX7A1 19 36642720 -0.83 0 0 10 0.47
cg23352695 EVI2A 17 29648811 -0.82 0 0 5.7 0.87
cg27049766 ZNF154 19 58220516 -0.81 0 0 6.4 0.14
cg02358862 CORO1A 16 30197211 -0.81 0 0 8.1 0.86
cg16983159 TMEM173 5 138862441 -0.8 0 0 8.6 0.58
cg14137939 CCDC89 11 85397109 -0.8 0 0 2.5 0.51
cg26350754 HLA-DPB1 6 33043868 -0.79 0 0 11 0.69
cg00404025 WDFY4 10 49892741 -0.79 0 0 5.9 0.77
cg02216727 GJD3 17 38520653 -0.79 0 0 5.5 0.84
cg10673833 MYO1G 7 45018849 -0.79 0 0 5.2 0.92
cg01681367 SPN 16 29676071 -0.79 0 0 5.7 0.88
cg06958535 LAX1 1 203734478 -0.79 2.9e-14 4.1e-13 1.7 0.91
cg09079252 FAM90A1 12 8380050 -0.79 0 0 2.9 0.72
cg09607452 ATP8B4 15 50193161 -0.79 0 0 8.2 0.54
cg26800884 KLB 4 39448008 -0.78 0 0 3.5 0.67
cg03089651 ARHGAP30 1 161039695 -0.78 0 0 7.2 0.69
cg12805374 FMNL1 17 43306622 -0.78 0 0 7.3 0.67
cg16066354 APOBEC3D 22 39417451 -0.78 0 0 4.9 0.42
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/KICH-TP/9830999/KICH-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/KICH-TP/9829954/KICH-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.