Skin Cutaneous Melanoma: 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 = 247. Number of gene expression samples = 249. Number of methylation samples = 249.

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 = 247

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
cg11578532 TSTD1 1 161008127 -0.89 0 0 5.100 0.673813
cg15518883 SIT1 9 35650561 -0.89 0 0 NA 0.746426
cg21171625 DNALI1 1 38022607 -0.88 0 0 5.299 0.558707
cg05462570 NAALADL1 11 64814948 -0.88 0 0 5.192 0.403122
cg02685484 PTPRCAP 11 67203360 -0.87 0 0 7.460 0.797418
cg20317872 DENND2D 1 111743202 -0.87 0 0 7.644 0.685386
cg03669949 DDX43 6 74104426 -0.87 5.9e-65 2.8e-65 NA 0.783239
cg16068833 CD52 1 26644515 -0.87 0 0 7.716 0.717353
cg07786657 CD247 1 167487633 -0.86 0 0 5.962 0.790416
cg01072786 GLB1L 2 220107847 -0.85 0 0 8.908 0.574488
cg11550547 KCTD14 11 77734490 -0.85 0 0 NA 0.661449
cg05564251 SP140 2 231090640 -0.84 0 0 6.107 0.718803
cg00032205 TSPYL5 8 98290372 -0.84 0 0 7.180 0.562198
cg21249754 PTPN6 12 7060206 -0.84 0 0 8.866 0.716378
cg07682037 FERMT3 11 63974153 -0.84 0 0 9.590 0.500736
cg00903584 PTPN7 1 202128682 -0.84 0 0 7.526 0.668813
cg12947833 HSPB2 11 111783499 -0.84 0 0 7.256 0.322635
cg25671438 ACAP1 17 7240223 -0.84 0 0 6.575 0.584593
cg16462073 LAT 16 28995843 -0.84 0 0 7.294 0.796873
cg10402417 TBC1D10C 11 67171476 -0.83 0 0 6.272 0.608150
cg05656364 VAMP8 2 85804732 -0.83 0 0 9.358 0.457425
cg07994485 FAM178B 2 97652440 -0.83 0 0 NA 0.666283
cg24612198 CD3E 11 118175631 -0.83 0 0 7.840 0.835844
cg04253799 LOC100128675 19 35597062 -0.83 0 0 NA 0.641216
cg07652628 KRT18 12 53343514 -0.83 0 0 7.937 0.653670
cg24674703 CD5 11 60869960 -0.83 0 0 6.303 0.763575
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/SKCM/2245202/0.GDAC_MethylationPreprocess.Finished/SKCM.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/SKCM/2245133/0.mRNAseq_preprocessor.Finished/SKCM.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.