Correlation between mRNA expression and DNA methylation
Acute Myeloid Leukemia (Primary blood derived cancer - Peripheral blood)
15 July 2014  |  analyses__2014_07_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/C1GH9GQ6
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 = 170. Number of gene expression samples = 173. Number of methylation samples = 194.

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 = 170

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
cg03758367 GTSF1 12 54867542 -0.88 0 0 7.2 0.63
cg11100640 MKRN3 15 23810861 -0.86 0 0 4.2 0.72
cg11763394 PAX8 2 113992921 -0.85 2.9e-48 1.3e-47 4.5 0.73
cg02296564 PRSS21 16 2867051 -0.85 0 0 5.6 0.65
cg08923054 ANK1 8 41654455 -0.84 0 0 8.3 0.82
cg11763394 LOC654433 2 113992921 -0.84 2.1e-42 9.4e-42 5.7 0.73
cg19083407 LOC654433 2 113993142 -0.84 5.5e-42 2.5e-41 5.7 0.7
cg11264499 MTX3 5 79286765 -0.84 0 0 7.7 0.49
cg03583857 CD34 1 208085022 -0.83 0 0 10 0.5
cg09015566 ZNF595 4 53264 -0.82 0 0 6.5 0.67
cg09032544 CD247 1 167487295 -0.82 8.1e-43 3.7e-42 6.7 0.89
cg13430807 MTMR11 1 149903315 -0.82 0 0 5.3 0.77
cg09233395 TRPS1 8 116678582 -0.82 0 0 8.5 0.52
cg05564251 SP140 2 231090640 -0.81 0 0 7.2 0.7
cg19083407 PAX8 2 113993142 -0.81 2e-40 9.3e-40 4.5 0.7
cg04927537 LGALS3BP 17 76976091 -0.81 0 0 9.8 0.44
cg01891966 HOXA9 7 27202344 -0.81 0 0 8.6 0.33
cg20894963 CLECL1 12 9885564 -0.81 0 0 5.6 0.73
cg03046812 SLC41A1 1 205781722 -0.81 0 0 7.6 0.45
cg09421562 MPO 17 56357994 -0.81 0 0 15 0.54
cg07483304 HOXA10 7 27211741 -0.8 0 0 7.7 0.22
cg08296037 TMEM204 16 1584118 -0.8 0 0 4.9 0.64
cg08926642 PER3 1 7887455 -0.8 0 0 6.3 0.82
cg18636641 PPAPDC3 9 134165268 -0.79 0 0 3.4 0.61
cg11538128 ZNF354C 5 178487481 -0.79 0 0 5.2 0.19
cg07728874 CD3D 11 118213272 -0.79 0 0 6.6 0.75
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/LAML-TB/9831245/LAML-TB.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/LAML-TB/9830100/LAML-TB.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.