Lung Adenocarcinoma: Correlation between mRNA expression and DNA methylation
Maintained by Richard Park (Boston University/Harvard Medical School)
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 = 181. Number of gene expression samples = 230. Number of methylation samples = 181.

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 = 181

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 -0.93 0 0 6.482 0.751952
cg04511534 GGT6 17 4463371 -0.87 0 0 NA 0.636164
cg03669949 DDX43 6 74104426 -0.86 0 0 NA 0.783243
cg24580782 NR0B2 1 27240365 -0.85 0 0 NA 0.767199
cg07135629 AQP1 7 30951709 -0.85 0 0 12.540 0.692511
cg07786657 CD247 1 167487633 -0.83 0 0 6.748 0.779302
cg24612198 CD3E 11 118175631 -0.83 0 0 8.451 0.879097
cg15677087 SLC17A9 20 61584850 -0.83 0 0 7.622 0.675373
cg09643186 GPX2 14 65409452 -0.82 0 0 7.379 0.663011
cg04983151 ALS2CR11 2 202483704 -0.82 0 0 NA 0.822555
cg12889195 PAX8 2 113992843 -0.82 3.3e-45 2.9e-45 NA 0.751952
cg04420917 LGALS4 19 39303993 -0.81 0 0 NA 0.663505
cg00032205 TSPYL5 8 98290372 -0.81 0 0 8.913 0.373831
cg05585149 C10orf108 10 695844 -0.81 0 0 NA 0.649014
cg24520381 PPP1R1B 17 37784694 -0.81 0 0 NA 0.639203
cg14900031 S100P 4 6695377 -0.81 0 0 10.002 0.542608
cg11683242 LCK 1 32716557 -0.81 0 0 7.790 0.841754
cg01232511 PRSS21 16 2867446 -0.81 0 0 NA 0.670151
cg24040502 NLRP2 19 55477810 -0.8 0 0 7.230 0.678895
cg22720041 ZNF229 19 44952725 -0.8 0 0 NA 0.308482
cg14571493 EGF 4 110834401 -0.8 0 0 6.390 0.709079
cg01341572 HNF1A 12 121416512 -0.8 0 0 NA 0.682772
cg09215282 MSLN 16 811744 -0.8 0 0 NA 0.654261
cg07037032 AKR7A3 1 19614429 -0.8 0 0 NA 0.707540
cg18427856 KIAA1949 6 30652647 -0.8 0 0 10.552 0.523381
cg01902605 BHMT2 5 78366076 -0.8 7.5e-41 6.8e-41 NA 0.632260
Methods & Data
Input

Methylation Array Platforms: Illumina Infinium HumanMethylation27, Illumina DNA Methylation OMA002, Illumina DNA Methylation OMA003

  • methylation file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MethylationPreprocess/LUAD/2044238/0.GDAC_MethylationPreprocess.Finished/LUAD.meth.for_correlation.filtered_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/LUAD/2044200/0.mRNAseq_preprocessor.Finished/LUAD.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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.