LUSC/00: Correlate Expression with 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. Tumor-specific methylation changes are identified between the possible available platforms.

Summary

The top 25 and bottom 25 methylation probe/gene pairs are displayed.

Results
Correlation Histogram

Figure 1.  Histogram of correlation values. n is the number of matched samples between Level 3 CpG site methylation and Level 3 gene expression arrays.

Negative Correlation between Methylation and Gene Expression

Table 1.  Get Full Table Top 25 most negatively correlated methylation probe/gene pairs. 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 Chromosome Position Correlation_Spearman Pvalue_Spearman Correlation_Pearson Pvalue_Pearson Expression_Mean Methylation_Mean Expression_Var Methylation_Var
cg16363586 BST2 19 17377329 -0.8687 0 -0.8683 1.013e-41 3.011e-01 0.48355 1.77647 5.703e-02
cg08124399 DDX43 6 74161589 -0.8274 0 -0.8261 1.934e-34 -1.529e+00 0.74000 1.81164 2.460e-02
cg08675664 ALDH7A1 5 125958769 -0.8159 0 -0.8302 4.666e-35 -7.047e-01 0.35307 1.69999 5.571e-02
cg23234999 MKRN3 15 21362298 -0.8069 0 -0.8096 4.226e-32 -1.594e+00 0.62861 0.47960 1.796e-02
cg09645888 ME3 11 86061233 -0.8059 0 -0.7801 1.844e-28 -6.225e-01 0.40868 0.62376 6.945e-02
cg03969797 MKRN3 15 21361757 -0.802 0 -0.7915 8.408e-30 -1.594e+00 0.37347 0.47960 2.872e-02
cg00141162 HCLS1 3 122862467 -0.7951 0 -0.8128 1.559e-32 1.494e+00 0.36871 1.13819 4.046e-02
cg15149645 NUPR1 16 28458120 -0.7855 0 -0.7653 7.817e-27 1.946e+00 0.54608 0.93889 4.017e-02
cg24169822 HOXA4 7 27137519 -0.7854 0 -0.7626 1.504e-26 -4.562e-01 0.50109 1.30245 3.926e-02
cg22497867 MAGEA4 X 150831952 -0.7817 0 -0.7769 4.228e-28 1.889e-01 0.71874 8.57927 2.052e-02
cg17188169 DDX43 6 74161109 -0.7761 0 -0.8113 2.453e-32 -1.529e+00 0.72426 1.81164 1.980e-02
cg00186701 TSPYL5 8 98359686 -0.7756 0 -0.7888 1.807e-29 1.786e+00 0.32647 3.00023 4.882e-02
cg13500819 MGC29506 5 138753299 -0.7688 0 -0.7824 1.013e-28 -3.702e-01 0.74419 1.37659 6.675e-03
cg05590982 NUPR1 16 28457672 -0.7671 0 -0.7474 5.027e-25 1.946e+00 0.42645 0.93889 2.556e-02
cg05740244 LDHC 11 18390591 -0.7596 0 -0.752 2.72e-25 -1.252e+00 NA 0.85198 NA
cg15518883 SIT1 9 35640561 -0.7564 0 -0.7809 1.508e-28 -4.257e-01 0.76304 0.55858 5.912e-03
cg15747595 TSPYL5 8 98359056 -0.7551 0 -0.749 3.528e-25 1.786e+00 0.40308 3.00023 4.783e-02
cg13702536 GPR81 12 121781506 -0.7535 0 -0.7741 8.654e-28 -1.009e+00 0.57121 1.46153 5.038e-02
cg13448625 COL17A1 10 105835228 -0.7525 0 -0.7648 8.799e-27 1.054e+00 0.58250 3.10471 2.941e-02
cg18738906 SCNN1A 12 6354000 -0.7515 0 -0.6926 2.607e-20 9.926e-01 0.73460 1.63749 4.024e-02
cg10146929 HIST1H1A 6 26125918 -0.7473 0 -0.6756 4.623e-19 -5.891e-01 0.45525 0.88270 4.608e-02
cg13840968 CIDEB 14 23850766 -0.7438 0 -0.7258 4.915e-23 -4.890e-01 0.54818 0.40228 3.055e-02
cg09522147 KRT7 12 50913609 -0.7428 0 -0.7818 1.197e-28 -7.882e-02 0.60693 1.39892 4.755e-02
cg04759756 SLA2 20 34707347 -0.7421 0 -0.6698 1.194e-18 -1.930e-01 0.83468 0.50293 3.399e-03
cg05508084 ZNF667 19 61680210 -0.741 0 -0.7227 9.231e-23 -1.858e+00 0.37986 0.79780 4.780e-02
cg06425515 ADH7 4 100575058 -0.736 0 -0.746 1.106e-21 3.035e+00 NA 8.57200 NA
Positive Correlation between Methylation and Gene Expression

Table 2.  Get Full Table Top 25 most positively correlated methylation probe/gene pairs. Correlation Coefficient: See Methods & Data below. Expression Median and Expression Variance: median and variance of gene expression levels of gene expression probes associated with the gene. Methylation Median and Methylation Variance: median and variance of methylation levels of CpG methylation probes associated with the gene.

Meth_Probe Gene Chromosome Position Correlation_Spearman Pvalue_Spearman Correlation_Pearson Pvalue_Pearson Expression_Mean Methylation_Mean Expression_Var Methylation_Var
cg09099744 CDKN2A 9 21958372 0.7834 0 0.8555 0 -3.138e-01 0.45748 3.34545 5.393e-02
cg10895543 CDKN2A 9 21958832 0.7795 0 0.8077 0 -3.138e-01 0.43284 3.34545 4.150e-02
cg07752420 CDKN2A 9 21958681 0.7725 0 0.8105 0 -3.138e-01 0.42216 3.34545 3.723e-02
cg12232463 LONRF2 2 100293082 0.762 0 0.7592 0 -2.455e+00 NA 2.48130 NA
cg11653709 CDKN2A 9 21958146 0.7288 0 0.7463 0 -3.138e-01 0.40547 3.34545 2.230e-02
cg01785568 MSX1 4 4915734 0.7272 0 0.622 1.332e-15 -1.065e+00 0.54898 0.84677 2.169e-02
cg04825431 ZNF239 10 43383905 0.6417 0 0.6236 1.11e-15 -6.515e-01 0.69267 1.28305 1.934e-02
cg09480837 PLCE1 10 95779491 0.6284 0 0.568 1.004e-12 -9.486e-01 0.66802 0.76046 2.220e-02
cg05813234 RPS6KA6 X 83342028 0.6144 0 0.621 5.329e-15 -1.056e+00 NA 0.74669 NA
cg00955451 APBA2 15 27000932 0.5854 0 0.5351 3.23e-11 -7.838e-01 0.69442 0.41528 1.706e-02
cg00037763 SETBP1 18 40535761 0.578 0 0.612 4.885e-15 -3.197e-02 0.79852 1.01477 1.591e-02
cg05341878 RIMS2 8 104900822 0.5717 0 0.5486 8.117e-12 -2.083e-01 0.43629 0.77752 3.049e-02
cg09630404 STAR 8 38127700 0.5701 0 0.5078 4.402e-10 -1.675e+00 0.45943 2.55312 3.871e-02
cg09847584 RIMBP2 12 129568339 0.5688 0 0.4792 5.384e-09 -1.264e+00 0.69162 0.83016 2.937e-02
cg11871280 SLC16A7 12 58368305 0.5537 0 0.539 2.596e-11 -9.598e-01 NA 0.61891 NA
cg20840847 APBA2 15 27000918 0.5442 0 0.5055 5.449e-10 -7.838e-01 0.74734 0.41528 1.974e-02
cg25216696 GATA4 8 11602760 0.5435 0 0.4659 1.597e-08 -1.830e+00 0.51912 0.31365 2.832e-02
cg24272907 RIMBP2 12 129568871 0.5371 0 0.5909 1.088e-13 -1.264e+00 NA 0.83016 NA
cg01671575 PGBD5 1 228580189 0.5355 0 0.5324 4.219e-11 -2.596e-01 0.78728 1.59392 1.621e-02
cg26917999 LZTS1 8 20157170 0.532 1.181e-11 0.53 5.389e-11 -1.608e+00 0.62784 0.20122 1.288e-02
cg24363955 C5orf23 5 32824224 0.5244 8.386e-11 0.5352 3.21e-11 9.849e-01 0.71676 2.40826 2.721e-02
cg01112778 PPP2R2B 5 146441180 0.5181 2.067e-10 0.56 2.42e-12 -5.569e-01 0.50892 1.33396 1.923e-02
cg10562586 MAP2 2 210152399 0.5177 2.167e-10 0.4928 1.68e-09 -5.865e-02 0.48246 1.09597 3.155e-02
cg16194715 SMAD9 13 36351926 0.5165 2.494e-10 0.492 1.81e-09 -1.810e+00 0.76300 0.33587 1.320e-02
cg02844051 DMKN 19 40696073 0.5106 4.867e-10 0.6033 1.51e-14 6.192e-02 0.77925 2.44621 1.731e-02
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-genepattern/jobResults/11347/PR_GDAC_GBM.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-genepattern/jobResults/11323/PR_GDAC_GBM.transcriptome__ht_hg_u133a__broad_mit_edu__Level_3__gene_rma__data.data.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.

  • correlation measure = Spearman