Brain Lower Grade Glioma: 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 = 44. Number of gene expression samples = 47. Number of methylation samples = 44.

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 = 44

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
cg11763394 LOC654433 2 113709392 -0.94 0 0 NA 0.863358
cg21550016 PAX8 2 113709401 -0.93 0 0 NA 0.854498
cg07326438 SLC43A3 11 56951138 -0.92 0 0 8.1731 0.502720
cg05804949 C7orf46 7 23686145 -0.92 0 0 6.1555 0.521194
cg00056767 CCDC122 13 43351183 -0.91 0 0 3.3319 0.531428
cg02304092 FLJ44606 5 126437126 -0.91 0 0 3.7713 0.451545
cg05491852 KIAA0495 1 3653692 -0.9 0 0 7.5776 0.479399
cg09684846 FAM18A 16 10820219 -0.9 0 0 6.9494 0.475293
cg19775206 C14orf86 14 93463471 -0.9 0 0 NA 0.723781
cg09721739 NMNAT3 3 140879614 -0.89 0 0 6.0440 0.506889
cg12835949 SSH3 11 66827322 -0.89 0 0 6.9177 0.544501
cg10859966 KHNYN 14 23968832 -0.89 0 0 8.4136 0.643058
cg11501236 LOC134466 5 150306271 -0.89 0 0 5.9570 0.161711
cg11166108 LDHA 11 18373343 -0.89 0 0 11.2885 0.367834
cg02407048 PION 7 76884070 -0.89 0 0 6.4045 0.690239
cg05968601 PGCP 8 97726435 -0.89 0 0 7.8279 0.603080
cg27240008 MBP 18 72857822 -0.89 0 0 14.0269 0.859782
cg00948524 RNF135 17 26321883 -0.89 0 0 7.2913 0.512254
cg00420361 ZDHHC1 16 66007438 -0.89 0 0 6.6357 0.372478
cg20414098 SLC25A45 11 64906735 -0.89 0 0 5.2437 0.582316
cg03208951 EMP3 19 53520647 -0.88 0 0 6.9199 0.597103
cg03452174 RAB34 17 24069240 -0.88 0 0 7.5914 0.644889
cg05941778 DUSP10 1 219980199 -0.88 0 0 6.8869 0.750071
cg27394566 PLD4 14 104462680 -0.88 0 0 8.7889 0.787839
cg16662267 CBR1 21 36364629 -0.88 0 0 9.8580 0.506861
cg23257225 ADORA1 1 201389767 -0.87 0 0 9.8912 0.747887
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/LGG/1841501/0.GDAC_MethylationPreprocess.Finished/LGG.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/LGG/1768792/0.mRNAseq_preprocessor.Finished/LGG.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.