LUAD/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
cg00916635 PTPN22 1 114215835 -0.7719941 1.267e-06 -0.6963275 9.599e-06 7.241e-01 0.43829 0.94692 2.772e-02
cg14385738 PTPN22 1 114215863 -0.7716276 1.278e-06 -0.7057917 6.412e-06 7.241e-01 0.38224 0.94692 3.173e-02
cg09643186 GPX2 14 64479205 -0.7536657 2.069e-06 -0.7632233 3.78e-07 -9.504e-01 0.74549 9.17721 3.453e-02
cg03699566 FOLR1 11 71578300 -0.7456012 2.682e-06 -0.7699809 2.573e-07 5.310e-01 0.49274 2.83223 2.354e-02
cg18846362 CA12 15 61461212 -0.7379032 3.501e-06 -0.4062126 0.02106 -1.411e+00 0.06550 1.94318 1.668e-03
cg22387994 NAPA 19 52710012 -0.707478 1.091e-05 -0.7544907 6.104e-07 -1.482e-01 0.06683 0.28601 1.441e-04
cg02659086 GSTP1 11 67107552 -0.6880499 2.249e-05 -0.6618126 3.708e-05 6.158e-01 0.07756 0.58559 3.399e-04
cg22266967 S100P 4 6746599 -0.6865836 2.372e-05 -0.7245699 2.745e-06 -9.451e-02 0.59329 8.54109 3.503e-02
cg11070419 C4BPA 1 205343833 -0.6818182 2.816e-05 -0.6831679 1.641e-05 3.988e+00 0.47692 3.75931 2.031e-02
cg16907075 UBQLN4 1 154289499 -0.6682551 4.532e-05 -0.6040266 0.0002516 -4.940e-01 0.12659 0.30378 1.188e-03
cg05508084 ZNF667 19 61680210 -0.6609238 5.813e-05 -0.6735985 2.384e-05 -1.280e+00 0.39223 1.02828 2.472e-02
cg07717632 C9orf167 9 139292452 -0.6605572 5.885e-05 -0.6555634 4.65e-05 -8.044e-01 0.20680 0.82887 2.879e-02
cg08209133 SLC10A4 4 48180381 -0.6590909 6.181e-05 -0.6339264 9.803e-05 -1.119e+00 0.31600 2.92918 1.421e-02
cg17188169 DDX43 6 74161109 -0.6535924 7.413e-05 -0.7163664 4.009e-06 -4.442e-01 0.74468 4.72021 1.867e-02
cg02599225 C10orf57 10 81828453 -0.6502933 8.253e-05 -0.6027011 0.0002618 6.082e-01 0.04212 0.32766 9.046e-05
cg21750589 ZNF323 6 28429280 -0.6499267 8.352e-05 -0.677093 2.084e-05 2.058e+00 0.44278 1.77162 1.195e-02
cg07311845 TMLHE X 154495930 -0.646261 9.397e-05 -0.6418802 7.502e-05 -7.284e-01 0.32665 1.01986 2.824e-02
cg11261264 PTPRH 19 60412549 -0.6458944 9.507e-05 -0.6324125 0.0001031 -1.434e+00 0.60350 2.06395 1.695e-02
cg03289872 ZNF667 19 61680914 -0.6396628 0.0001158 -0.6614748 3.754e-05 -1.280e+00 0.35059 1.02828 3.235e-02
cg01959004 HYOU1 11 118433621 -0.6381965 0.0001212 -0.5200803 0.00228 -6.504e-01 0.06973 0.24064 3.365e-04
cg06489418 FTSJ1 X 48219666 -0.6378299 0.0001226 -0.5875239 0.000407 -1.005e+00 0.38259 0.14661 6.210e-02
cg13840968 CIDEB 14 23850766 -0.6370968 0.0001254 -0.6729068 2.448e-05 -4.414e-01 0.62768 0.23371 1.743e-02
cg21614638 DAPP1 4 100956844 -0.6359971 0.0001297 -0.6772374 2.072e-05 1.227e+00 0.29825 1.02760 1.472e-02
cg11422541 ADCY6 12 47468853 -0.6315982 0.0001484 -0.6698265 2.752e-05 -8.628e-01 0.07736 0.27396 3.214e-04
cg12699145 TMC7 16 18903138 -0.6304985 0.0001535 -0.5322983 0.001713 -4.621e-01 0.14460 0.41309 4.869e-03
cg06458239 ZNF549 19 62730385 -0.6239003 0.0001871 -0.705452 6.508e-06 -5.965e-01 0.32036 1.27054 2.707e-02
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
cg26583078 SORBS2 4 187114772 0.6319648 0.0001468 0.5993724 0.0002889 8.146e-01 0.80333 2.13367 2.469e-03
cg00436603 CYP2E1 10 135190730 0.5975073 0.0003963 0.5456031 0.001239 -5.259e-01 0.59384 1.05369 1.201e-02
cg22901840 DIRAS3 1 68285365 0.5920088 0.0004598 0.5275886 0.001915 1.320e+00 0.70996 2.26021 7.799e-03
cg18780284 SPRR1B 1 151270946 0.5817449 0.0006028 0.4229204 0.01588 1.121e+00 0.47960 7.25310 2.547e-02
cg24884084 SPRR1B 1 151269822 0.5736804 0.0007414 0.4247493 0.01539 1.121e+00 0.29119 7.25310 7.887e-03
cg19273182 PAPOLG 2 60836921 0.5678152 0.000859 0.5986433 0.0002952 9.370e-01 0.05034 0.27105 6.858e-05
cg15534366 CDH4 20 59259602 0.5531525 0.001228 0.3466569 0.05193 -1.967e+00 0.59725 1.77258 2.045e-02
cg05023116 NLRP5 19 61202704 0.5491202 0.001351 0.3285509 0.06636 -7.700e-01 0.81268 1.02787 1.148e-02
cg25426743 HOXA3 7 27132628 0.5483871 0.001375 0.4402045 0.01169 2.665e-01 0.66837 0.84922 1.439e-02
cg15522719 GLS 2 191453493 0.5480205 0.001386 0.5105346 0.002831 1.268e+00 0.05503 1.47706 1.828e-04
cg21840599 PAK2 3 197951851 0.545088 0.001485 0.5122777 0.002722 -3.541e-01 0.05503 0.25810 6.361e-05
cg12100077 KLHL7 7 23111737 0.5370235 0.001788 0.5463793 0.001215 -7.300e-02 0.05107 0.39013 1.015e-04
cg03605761 RNF126 19 614973 0.5326246 0.001975 0.5406935 0.001399 -5.068e-01 0.53152 0.11351 1.869e-02
cg05482722 UTP14C 13 51496176 0.5326246 0.001975 0.5663584 0.0007274 3.008e-01 0.89260 0.21766 4.337e-04
cg16854606 DAND5 19 12941743 0.5164956 0.002815 0.249777 0.168 -2.280e+00 0.64868 0.52890 9.837e-03
cg05492113 TUB 11 8016908 0.5124633 0.003068 0.5543312 0.0009946 -1.355e+00 0.61429 0.45112 1.254e-02
cg22587758 SAA4 11 18214899 0.5095308 0.003265 0.524033 0.002081 -2.439e+00 0.57614 1.74007 1.072e-02
cg24167928 UTP14C 13 51496903 0.5043988 0.003635 0.4802893 0.0054 3.008e-01 0.84526 0.21766 1.172e-03
cg13192155 ERAS X 48570887 0.4978006 0.004164 0.4292578 0.01422 2.213e-02 0.70433 0.20540 8.803e-03
cg24929834 C22orf31 22 27787241 0.4978006 0.004164 0.3784687 0.03268 2.559e-01 0.74022 0.41334 5.409e-03
cg15013019 LYL1 19 13074451 0.4956012 0.004354 0.5338554 0.00165 -8.045e-01 0.14989 0.20346 2.824e-03
cg03641225 DIRAS3 1 68285127 0.4952346 0.004387 0.4733473 0.006214 1.320e+00 0.43446 2.26021 1.460e-02
cg00688421 RAP1GDS1 4 99400943 0.4904692 0.004828 0.4708623 0.006529 3.565e-01 0.05743 0.27725 8.053e-05
cg22238923 DOK1 2 74635095 0.4893695 0.004935 0.3899629 0.02736 1.646e-01 0.04082 0.11821 3.732e-05
cg27641018 EPDR1 7 37926280 0.4827713 0.005623 0.4592119 0.008197 5.849e-01 0.68485 1.31019 1.166e-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