Correlation between mRNA expression and DNA methylation
Sarcoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
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/C1G15Z98
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 = 103. Number of gene expression samples = 103. Number of methylation samples = 127.

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 = 103

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
cg18139641 CSRP1 1 201470467 -0.91 0 0 14 0.46
cg24691453 S100A4 1 153518384 -0.9 0 0 10 0.55
cg00329300 TSTD1 1 161008462 -0.89 0 0 5.3 0.53
cg24749672 BIN2 12 51718108 -0.88 0 0 6.7 0.84
cg25719851 PTPN6 12 7055452 -0.86 0 0 8.5 0.75
cg07675031 SPI1 11 47399893 -0.86 0 0 9 0.84
cg07682037 FERMT3 11 63974153 -0.86 0 0 8.9 0.67
cg02395102 ITGA7 12 56098977 -0.86 0 0 11 0.54
cg18523477 RBM38 20 55967503 -0.85 0 0 10 0.29
cg12494355 TPM2 9 35688020 -0.85 0 0 13 0.49
cg26303870 ACTN1 14 69443683 -0.85 0 0 13 0.39
cg03874653 MYLK 3 123380206 -0.85 0 0 13 0.27
cg21168101 HSPB3 5 53752133 -0.85 0 0 5.8 0.59
cg21583694 TGFBI 5 135365401 -0.85 0 0 12 0.7
cg23207527 RBM24 6 17283113 -0.84 0 0 7.3 0.47
cg18653451 CCDC8 19 46917018 -0.84 0 0 7.4 0.39
cg23973885 MXRA8 1 1294881 -0.84 0 0 12 0.55
cg05044173 CD4 12 6898500 -0.84 0 0 10 0.71
cg26899399 LMOD1 1 201914027 -0.84 0 0 11 0.42
cg06096184 LRIG1 3 66549732 -0.84 0 0 11 0.22
cg11609668 TAGLN 11 117075078 -0.84 0 0 14 0.71
cg02619478 RBPMS 8 30248018 -0.84 0 0 11 0.68
cg04882759 MYOCD 17 12569901 -0.83 0 0 6.9 0.54
cg21088259 METRNL 17 81039990 -0.83 0 0 9.9 0.67
cg23352695 EVI2A 17 29648811 -0.83 0 0 8 0.67
cg16386293 ECM1 1 150480856 -0.83 0 0 10 0.52
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/6154778/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/6044633/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.