Correlation between mRNA expression and DNA methylation
Liver Hepatocellular Carcinoma
14 July 2016  |  awg_lihc__2016_07_14
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/C1RV0N62
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 = 371. Number of gene expression samples = 423. Number of methylation samples = 429.

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 = 371

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
cg12889195 LOC654433 2 113992843 -0.89 1.5e-124 7.3e-125 5.8 0.75
cg06907626 NPC1L1 7 44580809 -0.85 0 0 8.4 0.56
cg04875514 SOAT2 12 53497147 -0.82 1.1e-89 5.5e-90 5.6 0.48
cg02512860 CLDN15 7 100880751 -0.82 0 0 9.4 0.48
cg19664267 B3GALT4 6 33245163 -0.81 0 0 5.9 0.56
cg05896042 RAB3D 19 11450090 -0.81 0 0 7.2 0.49
cg02096793 MFSD7 4 683148 -0.8 0 0 6.8 0.49
cg04218124 VIL1 2 219284345 -0.79 3e-81 1.4e-81 8.8 0.5
cg24046411 CYBA 16 88717646 -0.79 0 0 9.8 0.55
cg13466284 SFN 1 27189679 -0.79 0 0 7.5 0.58
cg12044599 PTPRCAP 11 67206308 -0.79 1.5e-79 7.3e-80 7 0.85
cg07364841 HGFAC 4 3444147 -0.78 0 0 8.7 0.69
cg17087669 MAPK13 6 36099123 -0.78 0 0 6.7 0.49
cg04145765 TRIM55 8 67039461 -0.78 0 0 8.4 0.48
cg03302951 RHOF 12 122230972 -0.77 0 0 6.4 0.57
cg08450017 CXCR6 3 45984838 -0.77 0 0 5.6 0.8
cg18749404 LGALS3BP 17 76975944 -0.77 0 0 13 0.45
cg26251270 GPX7 1 53067832 -0.77 0 0 6.7 0.29
cg02592271 KRTCAP3 2 27665507 -0.77 1.1e-70 5.3e-71 4.9 0.7
cg22721334 ZSCAN18 19 58609618 -0.76 0 0 8.5 0.29
cg03493668 THRSP 11 77776607 -0.76 0 0 7.7 0.65
cg27436259 PRSS8 16 31147017 -0.76 0 0 7 0.69
cg08036899 IFI27 14 94577218 -0.76 0 0 11 0.71
cg00239071 C14orf68 14 100789737 -0.75 0 0 9.6 0.75
cg01971407 IFITM1 11 313624 -0.75 0 0 10 0.54
cg14476101 PHGDH 1 120255992 -0.75 0 0 10 0.49
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/LIHC/26848840/LIHC.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/LIHC/26848775/LIHC.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.