Correlation between mRNA expression and DNA methylation
Skin Cutaneous Melanoma (Metastatic)
28 January 2016  |  analyses__2016_01_28
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/C1FF3RTK
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 = 367. Number of gene expression samples = 368. Number of methylation samples = 367.

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 = 367

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
cg21171625 DNALI1 1 38022607 -0.91 0 0 5.3 0.57
cg15518883 SIT1 9 35650561 -0.9 0 0 5.4 0.73
cg11578532 TSTD1 1 161008127 -0.9 0 0 5.2 0.66
cg07786657 CD247 1 167487633 -0.89 0 0 6.1 0.79
cg20317872 DENND2D 1 111743202 -0.89 0 0 7.7 0.67
cg16068833 CD52 1 26644515 -0.88 0 0 7.9 0.7
cg02423817 PTPRCAP 11 67203661 -0.88 0 0 7.7 0.72
cg05462570 NAALADL1 11 64814948 -0.87 0 0 5.2 0.41
cg10402417 TBC1D10C 11 67171476 -0.87 0 0 6.5 0.59
cg21249754 PTPN6 12 7060206 -0.86 0 0 9 0.71
cg00903584 PTPN7 1 202128682 -0.86 0 0 7.6 0.66
cg08075204 BIN2 12 51718112 -0.86 0 0 7.1 0.77
cg25671438 ACAP1 17 7240223 -0.86 0 0 6.8 0.57
cg01305625 PDLIM4 5 131593812 -0.85 0 0 7.8 0.7
cg07682037 FERMT3 11 63974153 -0.85 0 0 9.7 0.49
cg16462073 LAT 16 28995843 -0.84 0 0 7.5 0.79
cg05564251 SP140 2 231090640 -0.84 1.6e-100 5.1e-101 6.2 0.71
cg07994485 FAM178B 2 97652440 -0.84 0 0 6.4 0.67
cg10673833 MYO1G 7 45018849 -0.84 0 0 7.4 0.78
cg02358862 CORO1A 16 30197211 -0.84 1.8e-99 5.7e-100 10 0.69
cg12947833 HSPB2 11 111783499 -0.84 0 0 7.3 0.31
cg01072786 GLB1L 2 220107847 -0.84 0 0 8.8 0.59
cg11692409 SERPINF1 17 1665181 -0.84 0 0 12 0.55
cg00032205 TSPYL5 8 98290372 -0.84 0 0 7 0.56
cg23612220 TNFAIP8L2 1 151129298 -0.83 0 0 6.2 0.76
cg17078393 LCK 1 32717002 -0.83 0 0 7.1 0.81
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/SKCM-TM/22312672/SKCM-TM.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/SKCM-TM/22311291/SKCM-TM.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.