Colon/Rectal Adenocarcinoma: Correlation between mRNA expression and DNA methylation
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 = 6. Number of gene expression samples = 83. Number of methylation samples = 6.

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 = 6

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
cg12808596 ZP1 11 60397221 -1 0.017 0.014 NA 0.890588
cg25413843 VAX2 2 70980199 -1 0.017 0.014 NA 0.420550
cg03996398 TP53AIP1 11 128318652 -1 0.017 0.014 NA 0.902484
cg07710481 SLITRK5 13 87123385 -1 0.017 0.014 NA 0.551528
cg04140862 SLC8A3 14 69724392 -1 0.017 0.014 NA 0.600601
cg09634469 SERPIND1 22 19458411 -1 0.017 0.014 NA 0.914573
cg27312603 RDH8 19 9993713 -1 0.017 0.014 NA 0.926286
cg08143803 PROZ 13 112874198 -1 0.017 0.014 NA 0.853860
cg26746560 PLA2G3 22 29865672 -1 0.017 0.014 NA 0.348056
cg24162030 PKD2L1 10 102080579 -1 0.017 0.014 NA 0.310751
cg20210051 PDZRN4 12 40116333 -1 0.017 0.014 NA 0.113567
cg02949067 PCSK2 20 17411831 -1 0.017 0.014 NA 0.455140
cg02500479 PCDHA8 5 140244178 -1 0.017 0.014 NA 0.561196
cg15923943 PCDHA6 5 140363750 -1 0.017 0.014 NA 0.261005
cg08448812 PCDHA4 5 140187944 -1 0.017 0.014 NA 0.631587
cg06951122 PCDHA2 5 140202837 -1 0.017 0.014 NA 0.933020
cg26556719 PCDHA13 5 140241994 -1 0.017 0.014 NA 0.458073
cg02004641 PCDHA1 5 140286365 -1 0.017 0.014 NA 0.323209
cg15765486 PABPC4L 4 135342557 -1 0.017 0.014 NA 0.399130
cg18243017 ODZ2 5 167606874 -1 0.017 0.014 NA 0.589238
cg14401837 NPSR1 7 34664018 -1 0.017 0.014 NA 0.505999
cg23114866 NKX2-2 20 21442977 -1 0.017 0.014 NA 0.126644
cg15920887 MSTN 2 190636675 -1 0.017 0.014 NA 0.813143
cg00902427 MCHR1 22 39404937 -1 0.017 0.014 NA 0.564395
cg04256965 MAGEL2 15 21440054 -1 0.017 0.014 NA 0.898887
cg05687194 LRRC50 16 82735562 -1 0.017 0.014 NA 0.020203
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/COADREAD/1841454/0.GDAC_MethylationPreprocess.Finished/COADREAD.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/COADREAD/1768747/0.mRNAseq_preprocessor.Finished/COADREAD.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.