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 probe(s) per gene are displayed. Total number of matched samples = 223 Number of gene expression samples = 238 Number of methylation samples = 224

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 = 223

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 probe(s) per gene. Correlation Coefficient: See Methods & Data below. Expression Mean and Expression Variance: median and variance of gene expression levels of gene expression probes associated with the gene. Methylation Mean and Methylation Variance: median and variance of methylation levels of CpG methylation probes associated with the gene.

Meth_Probe | Gene | Chrom | Position | Corr_Spearman | Pval_Spearman | Qval | Expr_Mean | Meth_Mean
--- | --- | --- | --- | --- | --- | --- | --- | ---
cg16363586 | BST2 | 19 | 17377329 | -0.82 | 0 | 0 | -1.469e+00 | 0.58845
cg01570885 | FAM50B | 6 | 3794271 | -0.8 | 0 | 0 | 2.602e-02 | 0.59829
cg03202897 | FAM50B | 6 | 3794687 | -0.79 | 0 | 0 | 2.602e-02 | 0.65423
cg02512860 | CLDN15 | 7 | 100667471 | -0.78 | 0 | 0 | 5.794e-01 | 0.49380
cg19027571 | CHFR | 12 | 131973958 | -0.78 | 0 | 0 | -4.782e-01 | 0.39770
cg21820890 | PLA2G12B | 10 | 74384381 | -0.78 | 0 | 0 | 5.612e-01 | 0.64617
cg21614638 | DAPP1 | 4 | 100956844 | -0.78 | 0 | 0 | -7.250e-02 | 0.41205
cg18542098 | C19orf46 | 19 | 41191166 | -0.78 | 0 | 0 | 7.747e-01 | 0.54082
cg06791102 | ARHGAP4 | X | 152844794 | -0.77 | 0 | 0 | -1.327e+00 | 0.60165
cg06458239 | ZNF549 | 19 | 62730385 | -0.77 | 0 | 0 | -1.551e+00 | 0.49793
cg20775254 | PROM2 | 2 | 95304432 | -0.77 | 0 | 0 | 8.456e-01 | 0.57174
cg01333788 | GJB5 | 1 | 34993401 | -0.76 | 0 | 0 | 4.297e-01 | 0.55372
cg00338702 | CHFR | 12 | 131973767 | -0.76 | 0 | 0 | -4.782e-01 | 0.48827
cg15645309 | BATF | 14 | 75058500 | -0.75 | 7.6e-42 | 2.1e-40 | 2.705e-01 | NA
cg17349199 | C10orf82 | 10 | 118419442 | -0.75 | 0 | 0 | -3.493e-01 | 0.63511
cg27040423 | CHFR | 12 | 131974535 | -0.74 | 0 | 0 | -4.782e-01 | 0.31462
cg20176532 | ZNF256 | 19 | 63150791 | -0.74 | 0 | 0 | -1.527e+00 | 0.46012
cg07054095 | ZNF549 | 19 | 62730668 | -0.73 | 0 | 0 | -1.551e+00 | 0.49362
cg17615007 | ZNF134 | 19 | 62817301 | -0.73 | 0 | 0 | -9.283e-01 | 0.31658
cg25021247 | AMT | 3 | 49435166 | -0.73 | 0 | 0 | -2.715e-01 | 0.33930
cg05191071 | MRPS21 | 1 | 148532714 | -0.72 | 0 | 0 | -8.320e-01 | 0.43679
cg23653008 | CHFR | 12 | 131974492 | -0.72 | 0 | 0 | -4.782e-01 | 0.33260
cg13636404 | ZNF655 | 7 | 98993609 | -0.72 | 0 | 0 | -6.215e-01 | 0.20062
cg26201213 | MGMT | 10 | 131155786 | -0.72 | 0 | 0 | 2.923e-01 | 0.40029
cg20191453 | AMT | 3 | 49434859 | -0.72 | 0 | 0 | -2.715e-01 | 0.52464
cg03693099 | CEL | 9 | 134926722 | -0.71 | 0 | 0 | 9.772e-01 | 0.61775

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_MergeDataFilesPipeline/COADREAD/1444583/2.GDAC_MergeDataFiles.Finished/COADREAD.methylation__humanmethylation27__jhu_usc_edu__Level_3__within_bioassay_data_set_function__data.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/GDAC_mRNA_Preprocess_Median/COADREAD/1456483/0.GDAC_mRNA_Preprocess_Median.Finished/COADREAD.medianexp.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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