Correlation between mRNA expression and DNA methylation
Lung Adenocarcinoma (MOLECULAR_NONSMOKER)
07 February 2013  |  awg_luad__2013_02_07
Maintainer Information
Citation Information
Maintained by Richard Park (Boston University/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNA expression and DNA methylation. Broad Institute of MIT and Harvard. doi:10.7908/C15M63T3
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 = 63. Number of gene expression samples = 81. Number of methylation samples = 63.

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 = 63

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 -0.92 0 0 6.139 0.771827
cg04511534 GGT6 17 4463371 -0.89 0 0 NA 0.609583
cg03669949 DDX43 6 74104426 -0.87 0 0 NA 0.802302
cg25651476 NLRP2 19 55476717 -0.86 0 0 7.568 0.565960
cg24580782 NR0B2 1 27240365 -0.86 0 0 NA 0.746795
cg23894219 LOC441869 1 1356565 -0.86 0 0 8.542 0.555953
cg04420917 LGALS4 19 39303993 -0.86 0 0 NA 0.613338
cg11722581 C10orf108 10 695853 -0.86 0 0 3.415 0.559188
cg09643186 GPX2 14 65409452 -0.86 0 0 7.571 0.661533
cg07786657 CD247 1 167487633 -0.85 0 0 6.655 0.778757
cg06942685 ZNF542 19 56879432 -0.85 0 0 7.447 0.354117
cg09298971 SLC44A4 6 31846249 -0.85 0 0 11.140 0.620801
cg10580282 HYAL1 3 50340564 -0.85 0 0 7.885 0.610770
cg13714749 FAM83F 22 40391489 -0.84 0 0 5.134 0.533806
cg15677087 SLC17A9 20 61584850 -0.84 0 0 7.400 0.694218
cg02685484 PTPRCAP 11 67203360 -0.84 0 0 7.792 0.779164
cg14905657 LMO3 12 16760048 -0.84 0 0 10.370 0.450992
cg06100324 MSLN 16 811347 -0.83 0 0 10.146 0.716508
cg25571414 SLC34A2 4 25659572 -0.83 0 0 14.775 0.559255
cg13434570 CTSE 1 206317133 -0.83 0 0 11.332 0.729538
cg18307978 AQP1 7 30953124 -0.83 0 0 12.642 0.546460
cg24520381 PPP1R1B 17 37784694 -0.83 0 0 9.187 0.608808
cg12889195 PAX8 2 113992843 -0.82 0 0 5.777 0.771827
cg00032205 TSPYL5 8 98290372 -0.82 0 0 8.798 0.364396
cg03339560 AQP5 12 50357352 -0.82 0 0 8.546 0.615352
cg24612198 CD3E 11 118175631 -0.82 0 0 8.361 0.878109
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/MOLECULAR_NONSMOKER/2452438/0.GDAC_MethylationPreprocess.Finished/MOLECULAR_NONSMOKER.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/MOLECULAR_NONSMOKER/2452278/0.mRNAseq_preprocessor.Finished/MOLECULAR_NONSMOKER.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.