Skin Cutaneous Melanoma: Correlation between mRNA expression and DNA methylation
(NRAS_Hotspot_Mutants 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 = 62. Number of gene expression samples = 62. Number of methylation samples = 62.

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 = 62

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
cg15518883 SIT1 9 35650561 -0.92 0 0 NA 0.770256
cg07682037 FERMT3 11 63974153 -0.91 0 0 9.3912 0.519274
cg06133110 SCRN1 7 30028307 -0.9 0 0 10.5354 0.498709
cg03934354 C1QTNF3 5 34043140 -0.9 0 0 7.8348 0.740413
cg07786657 CD247 1 167487633 -0.9 0 0 5.7190 0.816158
cg13466383 TSTD1 1 161008705 -0.9 0 0 4.8955 0.661675
cg21171625 DNALI1 1 38022607 -0.9 0 0 4.4140 0.639586
cg20317872 DENND2D 1 111743202 -0.9 0 0 7.4156 0.730016
cg01072786 GLB1L 2 220107847 -0.9 0 0 8.9618 0.552766
cg16462073 LAT 16 28995843 -0.89 0 0 6.9412 0.820538
cg03669949 DDX43 6 74104426 -0.89 0 0 NA 0.740182
cg25671438 ACAP1 17 7240223 -0.89 0 0 6.2266 0.611554
cg10200291 FLJ44606 5 126409007 -0.89 0 0 NA 0.241351
cg24691453 S100A4 1 153518384 -0.88 0 0 10.3693 0.519821
cg20792833 PTPRCAP 11 67205195 -0.88 0 0 7.1365 0.709959
cg10236239 SULT1C4 2 108994514 -0.88 0 0 NA 0.611541
cg19917412 NAALADL1 11 64815189 -0.88 0 0 4.7905 0.561735
cg12889195 LOC654433 2 113992843 -0.88 0 0 5.8019 0.719485
cg26842815 PTPN6 12 7060263 -0.88 0 0 8.6520 0.612936
cg16068833 CD52 1 26644515 -0.88 0 0 7.5082 0.739704
cg01834022 EVC2 4 5710411 -0.87 0 0 6.7784 0.348324
cg21931938 PLCB2 15 40600493 -0.87 0 0 8.7708 0.460573
cg17394649 HCG4 6 29760164 -0.87 0 0 NA 0.408020
cg04253799 LOC100128675 19 35597062 -0.87 0 0 NA 0.657891
cg23178195 FXYD1 19 35629703 -0.87 0 0 NA 0.738798
cg10673833 MYO1G 7 45018849 -0.87 0 0 6.9769 0.812921
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-NRAS_Hotspot_Mutants/3155584/0.GDAC_MethylationPreprocess.Finished/SKCM-NRAS_Hotspot_Mutants.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-NRAS_Hotspot_Mutants/3154989/SKCM-NRAS_Hotspot_Mutants.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.