Bladder Urothelial Carcinoma: 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 = 74. Number of gene expression samples = 85. Number of methylation samples = 74.

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 = 74

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
cg00032205 TSPYL5 8 98359548 -0.88 0 0 8.500 0.33086
cg22040809 HCG11 6 26630557 -0.88 0 0 7.178 0.48911
cg16850945 TNNC1 3 52463269 -0.87 0 0 NA 0.56574
cg06360527 SOX15 17 7432272 -0.87 0 0 6.946 0.52485
cg12557114 WISP3 6 112482563 -0.87 0 0 NA 0.74935
cg03021690 TNFAIP2 14 102661717 -0.86 0 0 12.403 0.65537
cg21145686 GPD1L 3 32124157 -0.85 0 0 9.941 0.40229
cg12889195 LOC654433 2 113709314 -0.85 0 0 6.944 0.67063
cg09781936 TBX1 22 18129961 -0.85 0 0 6.788 0.61507
cg08036899 IFI27 14 93646971 -0.85 0 0 11.279 0.63671
cg25073793 FAM50B 6 3794701 -0.85 0 0 5.762 0.50733
cg16785938 SLC2A9 4 9632082 -0.85 0 0 7.272 0.46112
cg21330727 RAPGEFL1 17 35589732 -0.85 0 0 10.460 0.43769
cg15700022 PP14571 2 241044924 -0.84 0 0 NA 0.62599
cg04058748 SNX31 8 101727589 -0.84 0 0 NA 0.65316
cg22718139 HMGCS2 1 120112962 -0.84 0 0 NA 0.69493
cg06972565 TNFRSF21 6 47380699 -0.84 0 0 12.678 0.58953
cg16363586 BST2 19 17377329 -0.84 0 0 11.170 0.47011
cg10673833 MYO1G 7 44985374 -0.84 0 0 6.568 0.80979
cg18292904 MST1R 3 49914707 -0.83 0 0 8.247 0.67404
cg07693270 RPL39L 3 188339622 -0.83 0 0 4.974 0.62759
cg15694715 TMEM25 11 117907490 -0.83 0 0 8.220 0.39612
cg09053536 TBX3 12 113601934 -0.83 0 0 10.236 0.53590
cg26155983 GPX2 14 64479898 -0.83 0 0 NA 0.61576
cg03302951 RHOF 12 120715355 -0.82 0 0 7.462 0.45214
cg10088332 GTSF1 12 53153696 -0.82 0 0 NA 0.83284
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/BLCA/1841437/0.GDAC_MethylationPreprocess.Finished/BLCA.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/BLCA/1780753/0.mRNAseq_preprocessor.Finished/BLCA.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

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