Lung Adenocarcinoma: Correlation between mRNA expression and DNA methylation
(primary solid tumor cohort)
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 = 285. Number of gene expression samples = 353. Number of methylation samples = 285.

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 = 285

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 6.398 0.75125
cg07135629 AQP1 7 30951709 -0.88 0 0 12.281 0.70508
cg04511534 GGT6 17 4463371 -0.87 0 0 NA 0.64079
cg03669949 DDX43 6 74104426 -0.86 1.9e-83 9.2e-84 NA 0.79935
cg10055471 NR0B2 1 27240319 -0.84 0 0 NA 0.73232
cg05585149 C10orf108 10 695844 -0.83 0 0 NA 0.65614
cg05564251 SP140 2 231090640 -0.82 0 0 6.980 0.68024
cg12889195 PAX8 2 113992843 -0.82 2.8e-70 1.3e-70 NA 0.75125
cg07786657 CD247 1 167487633 -0.81 0 0 6.802 0.77458
cg09643186 GPX2 14 65409452 -0.81 0 0 7.312 0.66623
cg15677087 SLC17A9 20 61584850 -0.81 0 0 7.757 0.67127
cg15518883 SIT1 9 35650561 -0.81 0 0 NA 0.72194
cg04420917 LGALS4 19 39303993 -0.81 0 0 NA 0.66878
cg04983151 ALS2CR11 2 202483704 -0.81 0 0 NA 0.80781
cg00032205 TSPYL5 8 98290372 -0.8 0 0 9.004 0.35996
cg07037032 AKR7A3 1 19614429 -0.8 0 0 NA 0.69195
cg01232511 PRSS21 16 2867446 -0.8 0 0 NA 0.67103
cg14900031 S100P 4 6695377 -0.8 0 0 9.907 NA
cg02423817 PTPRCAP 11 67203661 -0.8 0 0 7.911 0.67742
cg24612198 CD3E 11 118175631 -0.8 0 0 8.456 0.87382
cg13975362 GPR116 6 46890512 -0.8 0 0 11.706 NA
cg01902605 BHMT2 5 78366076 -0.8 9.6e-64 4.5e-64 NA 0.62168
cg23234999 MKRN3 15 23811205 -0.8 0 0 NA 0.75588
cg23894219 LOC441869 1 1356565 -0.79 0 0 8.612 0.52178
cg04759756 SLA2 20 35273933 -0.79 0 0 6.046 0.80692
cg11683242 LCK 1 32716557 -0.79 0 0 7.853 0.83935
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-TP/2401820/0.GDAC_MethylationPreprocess.Finished/LUAD-TP.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-TP/2398243/0.mRNAseq_preprocessor.Finished/LUAD-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

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