Acute Myeloid Leukemia: Correlation between mRNA expression and DNA methylation
(primary blood tumor (peripheral) cohort)
Maintained by Richard Park (Boston University/Harvard Medical School)
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 = 176. Number of gene expression samples = 179. Number of methylation samples = 176.

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 = 176

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
cg06809675 GTSF1 12 54867312 -0.91 0 0 NA 0.622822
cg12889195 PAX8 2 113992843 -0.89 0 0 NA 0.738843
cg19083407 LOC654433 2 113993142 -0.87 0 0 NA 0.697146
cg11100640 MKRN3 15 23810861 -0.84 1.7e-40 5.5e-40 NA 0.722630
cg08923054 ANK1 8 41654455 -0.84 0 0 1.3471320 0.817606
cg13430807 MTMR11 1 149903315 -0.84 0 0 0.2214758 0.759756
cg03583857 CD34 1 208085022 -0.83 0 0 4.1557833 0.498661
cg09032544 CD247 1 167487295 -0.83 0 0 1.9844133 0.896050
cg11264499 MTX3 5 79286765 -0.83 0 0 0.3125175 0.481398
cg09233395 TRPS1 8 116678582 -0.81 0 0 1.2186037 0.515070
cg04927537 LGALS3BP 17 76976091 -0.81 0 0 4.4927778 0.447765
cg03046812 SLC41A1 1 205781722 -0.81 7.2e-43 2.3e-42 1.2533620 0.442307
cg20894963 CLECL1 12 9885564 -0.81 1.2e-42 4e-42 1.1508818 0.720786
cg05564251 SP140 2 231090640 -0.81 0 0 1.4414684 0.694071
cg09015566 ZNF595 4 53264 -0.81 0 0 NA 0.669026
cg09421562 MPO 17 56357994 -0.81 0 0 9.2542612 0.540532
cg11538128 ZNF354C 5 178487481 -0.8 0 0 -0.0410608 0.194558
cg01891966 HOXA9 7 27202344 -0.8 0 0 NA 0.331124
cg18636641 PPAPDC3 9 134165268 -0.8 6.7e-36 2.2e-35 NA 0.606295
cg07483304 HOXA10 7 27211741 -0.8 0 0 NA 0.215513
cg08296037 TMEM204 16 1584118 -0.79 2.3e-39 7.5e-39 0.6464647 0.638136
cg02954987 LAMB2 3 49170599 -0.79 0 0 1.5593932 0.541796
cg07728874 CD3D 11 118213272 -0.79 0 0 3.0200669 0.746278
cg08926642 PER3 1 7887455 -0.79 6.4e-39 2.1e-38 -0.1575505 0.818780
cg25651476 NLRP2 19 55476717 -0.79 0 0 0.0868823 0.613679
cg16235861 TMEM20 10 95653642 -0.79 1.7e-36 5.3e-36 NA 0.226735
Methods & Data
Input

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

  • methylation file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MethylationPreprocess/LAML-TB/2401695/0.GDAC_MethylationPreprocess.Finished/LAML-TB.meth.for_correlation.filtered_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/2398235/0.mRNAseq_preprocessor.Finished/LAML-TB.mRNAseq_RPKM_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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.