Glioblastoma Multiforme: 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 probe(s) per gene are displayed. Total number of matched samples = 279 Number of gene expression samples = 289 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 = 279

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
cg01305625 PDLIM4 5 131621711 -0.77 0 0 -0.61 0.60271
cg19904463 FABP5 8 82355161 -0.74 0 0 3.3 0.50277
cg19257200 SOX10 22 36710929 -0.71 0 0 -0.06 0.70035
cg23566503 NNAT 20 35583164 -0.69 0 0 0.28 0.70449
cg06614002 SOX10 22 36710385 -0.67 0 0 -0.06 0.76715
cg23265096 CTSZ 20 57015989 -0.66 0 0 -0.14 0.66747
cg16363586 BST2 19 17377329 -0.64 0 0 1.4 NA
cg06456031 TMEM140 7 134483390 -0.63 0 0 0.28 0.42618
cg23363832 RBP1 3 140741629 -0.63 0 0 2.4 0.29223
cg23539753 SP100 2 230988942 -0.63 0 0 -0.41 0.46014
cg18433380 NNAT 20 35582608 -0.63 0 0 0.28 0.72801
cg16638540 ZNF135 19 63262280 -0.62 0 0 -1.8 0.24653
cg05437059 KCNE1L X 108755431 -0.62 0 0 -0.77 0.56906
cg02794695 SLA 8 134141793 -0.62 0 0 1.1 0.72611
cg03625911 CHI3L1 1 201422360 -0.62 0 0 4.7 0.60350
cg20512303 PDLIM4 5 131620858 -0.62 0 0 -0.61 0.73893
cg24594997 RBP1 3 140740856 -0.61 0 0 2.4 0.17128
cg24211388 AIF1 6 31690816 -0.61 0 0 1.2 0.74966
cg07952391 THNSL2 2 88251288 -0.61 0 0 -1.2 0.34475
cg07816074 SH3TC1 4 8252460 -0.61 0 0 -0.96 0.79374
cg18806365 FABP5 8 82355364 -0.6 0 0 3.3 0.40606
cg10001720 LAPTM5 1 31003950 -0.6 0 0 3.4 0.73563
cg21350115 CALCRL 2 188021078 -0.6 4.5e-28 1.6e-26 -0.53 NA
cg06836736 ME1 6 84197712 -0.6 0 0 0.24 0.46371
cg24881834 ME1 6 84197716 -0.6 0 0 0.24 0.60740
cg01063813 STAT6 12 55791215 -0.6 0 0 -0.89 0.56932
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/GBM/1216749/2.GDAC_MergeDataFiles.Finished/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/jobResults/GDAC_mRNA_Preprocess_Median/GBM/1227634/0.GDAC_mRNA_Preprocess_Median.Finished/GBM.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

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.

Meta
  • Maintainer = Richard Park