Correlation between mRNA expression and DNA methylation
Acute Myeloid Leukemia (Primary blood derived cancer - Peripheral blood)
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/C11R6PXM
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
cg14870271 LGALS3BP 17 76976010 -0.84 0 0 9.8 0.39
cg22730830 PRSS21 16 2867434 -0.84 0 0 5.6 0.74
cg05564251 SP140 2 231090640 -0.84 0 0 7.2 0.75
cg03583857 CD34 1 208085022 -0.83 0 0 10 0.44
cg09421562 MPO 17 56357994 -0.81 0 0 15 0.51
cg04450876 GTSF1 12 54866945 -0.8 0 0 7.2 0.74
cg17901463 GSTM1 1 110230473 -0.8 0 0 5.6 0.23
cg15880738 CD3G 11 118215112 -0.79 0 0 5.7 0.81
cg18636641 PPAPDC3 9 134165268 -0.79 0 0 3.4 0.69
cg07728874 CD3D 11 118213272 -0.79 0 0 6.6 0.81
cg11375102 TMEM204 16 1583810 -0.77 0 0 4.9 0.51
cg01862366 TMEM20 10 95654158 -0.77 0 0 4.5 0.12
cg11538128 ZNF354C 5 178487481 -0.77 0 0 5.2 0.15
cg26511321 HOXA7 7 27196790 -0.77 0 0 7.1 0.15
cg18463686 CLEC5A 7 141646690 -0.76 0 0 7.7 0.61
cg08797194 UGGT2 13 96705123 -0.76 0 0 5.2 0.26
cg07152925 S100B 21 48024683 -0.75 0 0 5.5 0.74
cg20516209 EMILIN1 2 27301943 -0.75 0 0 7.7 0.61
cg07141002 H1F0 22 38201690 -0.74 0 0 9.7 0.61
cg01405107 HOXB5 17 46671635 -0.74 9.3e-25 2.7e-23 5.3 0.29
cg24949488 DNTT 10 98064362 -0.73 0 0 7.1 0.63
cg07611334 NRSN2 20 327811 -0.73 0 0 6.2 0.22
cg04228042 ART4 12 14996527 -0.73 0 0 3 0.86
cg07693270 RPL39L 3 186856928 -0.73 0 0 3.7 0.72
cg02096633 UNC13B 9 35162499 -0.72 0 0 6.2 0.12
cg18712919 RBKS 2 28112170 -0.72 0 0 6.4 0.49
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/22314769/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/22311226/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.