Correlation between mRNA expression and DNA methylation
Thyroid Adenocarcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
Maintained by Richard Park (Boston University/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between mRNA expression and DNA methylation. Broad Institute of MIT and Harvard. doi:10.7908/C1445KZ5
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 = 501. Number of gene expression samples = 501. Number of methylation samples = 503.

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 = 501

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
cg21188037 MYO1G 7 45018658 -0.9 0 0 8.4 0.54
cg24749672 BIN2 12 51718108 -0.89 0 0 6.4 0.88
cg11763394 LOC654433 2 113992921 -0.87 0 0 4.2 0.91
cg08480068 SPN 16 29674959 -0.87 0 0 6.9 0.89
cg21163717 DOK2 8 21769903 -0.86 0 0 6.3 0.81
cg25754958 PTPN7 1 202130692 -0.86 0 0 6 0.76
cg09897970 C16orf54 16 29757344 -0.86 7.9e-146 4.1e-146 4.6 0.85
cg25571414 SLC34A2 4 25659572 -0.86 0 0 14 0.6
cg09032544 CD247 1 167487295 -0.85 0 0 5.4 0.92
cg26648103 SYT12 11 66791718 -0.85 1.2e-139 6.1e-140 8.7 0.39
cg05564251 SP140 2 231090640 -0.85 5.8e-138 3e-138 4.7 0.83
cg07675031 SPI1 11 47399893 -0.84 0 0 8 0.9
cg22502856 LAMB3 1 209825678 -0.84 4.5e-136 2.3e-136 11 0.72
cg27398499 TACSTD2 1 59043873 -0.84 0 0 12 0.4
cg16983159 TMEM173 5 138862441 -0.84 0 0 10 0.35
cg23352695 EVI2A 17 29648811 -0.83 0 0 6.5 0.86
cg06799735 AHNAK2 14 105437141 -0.83 0 0 10 0.6
cg11787522 STRA6 15 74495109 -0.83 1.4e-130 7.1e-131 7.7 0.46
cg18738906 SCNN1A 12 6483739 -0.83 0 0 11 0.71
cg10397389 DAPP1 4 100738011 -0.83 4.9e-129 2.5e-129 4.8 0.8
cg19774846 RUNX3 1 25292225 -0.83 0 0 6.2 0.91
cg15761609 FAM20A 17 66598067 -0.83 0 0 10 0.31
cg24815934 ITGB2 21 46332181 -0.83 0 0 9.9 0.74
cg00041401 PTPN22 1 114414408 -0.82 0 0 4.7 0.78
cg25651476 NLRP2 19 55476717 -0.82 1e-123 5.3e-124 6.1 0.57
cg22821300 RASGRF1 15 79296585 -0.82 0 0 6.5 0.55
Methods & Data
Input

Methylation Array Platforms: Illumina Infinium HumanMethylation27, Illumina Infinium HumanMethylation450, Illumina DNA Methylation OMA002, Illumina DNA Methylation OMA003

  • methylation file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MethylationPreprocess/THCA-TP/22319967/THCA-TP.meth.by_min_expr_corr.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/THCA-TP/22319926/THCA-TP.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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.