Correlation between mRNA expression and DNA methylation
Sarcoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
Maintained by Richard Park (Boston University/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNA expression and DNA methylation. Broad Institute of MIT and Harvard. doi:10.7908/C1BZ6505
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 = 238. Number of gene expression samples = 257. Number of methylation samples = 242.

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 = 238

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
cg24749672 BIN2 12 51718108 -0.89 0 0 6.9 0.81
cg24691453 S100A4 1 153518384 -0.89 0 0 11 0.49
cg00329300 TSTD1 1 161008462 -0.86 0 0 5.5 0.56
cg26842815 PTPN6 12 7060263 -0.85 0 0 8.7 0.62
cg07682037 FERMT3 11 63974153 -0.85 0 0 9.1 0.65
cg18139641 CSRP1 1 201470467 -0.84 0 0 13 0.52
cg21583694 TGFBI 5 135365401 -0.84 0 0 13 0.66
cg08735211 HLA-DMA 6 32920657 -0.84 0 0 10 0.7
cg10673833 MYO1G 7 45018849 -0.84 0 0 6.9 0.84
cg18062140 RBM38 20 55967678 -0.83 0 0 9.7 0.39
cg21366673 HLA-E 6 30459512 -0.83 0 0 13 0.8
cg18653451 CCDC8 19 46917018 -0.83 0 0 7.6 0.34
cg05847586 SIX2 2 45235512 -0.82 0 0 7.2 0.39
cg12494355 TPM2 9 35688020 -0.82 0 0 13 0.55
cg19083407 LOC654433 2 113993142 -0.82 0 0 6.5 0.73
cg22328208 TSPYL5 8 98289745 -0.82 0 0 8.5 0.6
cg20609803 FCER1G 1 161184305 -0.82 0 0 9.3 0.82
cg16363586 BST2 19 17516329 -0.81 0 0 10 0.66
cg15982099 SPI1 11 47399813 -0.81 0 0 9.2 0.85
cg17736336 LOC728264 5 148788401 -0.81 0 0 8.7 0.46
cg23501051 LOC100126784 11 19736912 -0.81 0 0 6.3 0.37
cg19083407 PAX8 2 113993142 -0.81 0 0 5.3 0.73
cg24497819 SELPLG 12 109027683 -0.8 0 0 8.8 0.62
cg21088259 METRNL 17 81039990 -0.8 0 0 10 0.63
cg16083429 CCDC36 3 49237500 -0.8 0 0 4.5 0.58
cg17936488 FAM78A 9 134151519 -0.8 0 0 7.8 0.68
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/SARC-TP/11493923/SARC-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/SARC-TP/11493688/SARC-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.