Correlation between mRNA expression and DNA methylation
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 probe(s) per gene are displayed. Total number of matched samples = 313 Number of gene expression samples = 315 Number of methylation samples = 529

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 = 313

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 probe(s) per gene. Correlation Coefficient: See Methods & Data below. Expression Mean and Expression Variance: median and variance of gene expression levels of gene expression probes associated with the gene. Methylation Mean and Methylation Variance: median and variance of methylation levels of CpG methylation probes associated with the gene.

Meth_Probe Gene Chrom Position Corr_Spearman Pval_Spearman Qval Expr_Mean Meth_Mean
cg15518883 SIT1 9 35640561 -0.86 0 0 -7.705e-01 0.79928
cg24674703 CD5 11 60626536 -0.86 0 0 -5.636e-01 0.81197
cg05740244 LDHC 11 18390591 -0.81 0 0 -3.678e-01 NA
cg10045881 CHI3L2 1 111571814 -0.77 0 0 1.188e-02 0.47701
cg11584936 BNIPL 1 149276212 -0.76 0 0 1.938e+00 0.31498
cg07347645 SYCP2 20 57940566 -0.75 0 0 4.857e-01 0.49777
cg00083937 MAPK8IP2 22 49386671 -0.75 0 0 1.164e+00 0.50124
cg20792833 PTPRCAP 11 66961771 -0.75 0 0 6.558e-04 0.74735
cg24392574 CALML5 10 5531423 -0.75 0 0 5.981e-01 0.85287
cg11600161 TBC1D10C 11 66928161 -0.75 0 0 -6.352e-01 0.74207
cg09886641 SPESP1 15 67010072 -0.75 0 0 -5.392e-01 0.72197
cg22214414 SYCP2 20 57940627 -0.74 0 0 4.857e-01 0.54212
cg03534410 TMEM40 3 12776112 -0.74 0 0 9.764e-01 0.58588
cg16363586 BST2 19 17377329 -0.74 0 0 2.395e-01 0.38680
cg18738906 SCNN1A 12 6354000 -0.74 0 0 1.564e+00 0.66035
cg22266967 S100P 4 6746599 -0.74 0 0 -8.515e-01 0.53894
cg24841244 CD3D 11 117718540 -0.73 0 0 -2.799e+00 0.75201
cg09522147 KRT7 12 50913609 -0.73 0 0 1.689e+00 0.41206
cg17078393 LCK 1 32489589 -0.73 0 0 -1.960e+00 0.77617
cg09902130 CD6 11 60495754 -0.73 0 0 1.199e-01 0.81638
cg00328227 C1orf59 1 109005848 -0.72 0 0 -3.380e-01 0.37292
cg13840968 CIDEB 14 23850766 -0.72 0 0 5.331e-02 0.59608
cg07621046 C10orf82 10 118419648 -0.72 0 0 1.105e-01 0.53250
cg24926276 LRG1 19 4490943 -0.72 0 0 6.687e-01 0.37548
cg05982504 IGFALS 16 1784963 -0.72 0 0 1.535e+00 0.53917
cg23207527 RBM24 6 17391092 -0.71 0 0 1.005e-01 0.63109
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_MergeDataFilesPipeline/BRCA/1668809/2.GDAC_MergeDataFiles.Finished/BRCA.methylation__humanmethylation27__jhu_usc_edu__Level_3__within_bioassay_data_set_function__data.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/GDAC_mRNA_Preprocess_Median/BRCA/1676448/0.GDAC_mRNA_Preprocess_Median.Finished/BRCA.medianexp.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