Breast Invasive 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 = 510. Number of gene expression samples = 805. Number of methylation samples = 510.

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 = 510

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
cg12889195 LOC654433 2 113709314 -0.91 0 0 6.046 0.776389
cg12889195 PAX8 2 113709314 -0.86 0 0 5.118 0.776389
cg08261841 TMEM139 7 142692585 -0.84 0 0 6.544 0.746240
cg01586506 SOX10 22 36709452 -0.84 0 0 NA 0.850247
cg00032205 TSPYL5 8 98359548 -0.83 0 0 9.247 0.409253
cg13871633 ZNF662 3 42922389 -0.83 0 0 6.633 0.519413
cg00944649 C1orf64 1 16203440 -0.83 0 0 NA 0.644416
cg07945733 C10orf82 10 118419475 -0.83 0 0 NA 0.628972
cg03699843 SNX20 16 49258565 -0.83 3e-129 6.7e-130 5.331 0.797353
cg05564251 SP140 2 230798884 -0.83 0 0 5.946 0.788609
cg00903584 PTPN7 1 200395305 -0.82 0 0 6.987 0.756377
cg15518883 SIT1 9 35640561 -0.82 0 0 NA 0.792718
cg24674703 CD5 11 60626536 -0.81 0 0 6.282 0.829454
cg15937958 CXCL17 19 47638973 -0.81 0 0 NA 0.691267
cg08450017 CXCR6 3 45959842 -0.81 0 0 5.715 0.753057
cg07571745 LCK 1 32488015 -0.81 0 0 6.650 0.756461
cg07641284 C16orf54 16 29664452 -0.81 0 0 5.539 0.760897
cg25671438 ACAP1 17 7180947 -0.81 0 0 6.027 0.630720
cg09298971 SLC44A4 6 31954228 -0.81 0 0 NA 0.612599
cg19353949 PDZK1 1 144438336 -0.8 0 0 6.469 0.634825
cg10402417 TBC1D10C 11 66928052 -0.8 0 0 5.803 0.668401
cg18581405 S1PR4 19 3131035 -0.8 0 0 4.358 0.668847
cg15700022 PP14571 2 241044924 -0.8 0 0 NA 0.597261
cg14058239 SLC39A6 18 31960226 -0.8 0 0 13.863 0.693613
cg07786657 CD247 1 165754257 -0.8 0 0 5.764 0.816152
cg24506221 GSTM1 1 110031924 -0.8 0 0 NA NA
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/BRCA/1841444/0.GDAC_MethylationPreprocess.Finished/BRCA.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/BRCA/1768725/0.mRNAseq_preprocessor.Finished/BRCA.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.