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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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