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 113992843 -0.91 0 0 6.046 0.777078
cg12889195 PAX8 2 113992843 -0.86 0 0 5.118 0.777078
cg08261841 TMEM139 7 142982463 -0.84 0 0 6.544 0.746424
cg01586506 SOX10 22 38379506 -0.84 0 0 NA 0.850513
cg00032205 TSPYL5 8 98290372 -0.83 0 0 9.247 0.409566
cg13871633 ZNF662 3 42947385 -0.83 0 0 6.633 0.519641
cg00944649 C1orf64 1 16330853 -0.83 0 0 NA 0.644676
cg07945733 C10orf82 10 118429485 -0.83 0 0 NA 0.629700
cg03699843 SNX20 16 50701064 -0.83 3.4e-130 8.4e-131 5.331 0.797548
cg05564251 SP140 2 231090640 -0.82 0 0 5.946 0.788481
cg00903584 PTPN7 1 202128682 -0.82 0 0 6.987 0.756659
cg15518883 SIT1 9 35650561 -0.82 0 0 NA 0.792769
cg24674703 CD5 11 60869960 -0.82 0 0 6.282 0.829644
cg07641284 C16orf54 16 29756951 -0.81 0 0 5.539 0.761200
cg08450017 CXCR6 3 45984838 -0.81 0 0 5.715 0.752844
cg15937958 CXCL17 19 42947133 -0.81 0 0 NA 0.691287
cg25671438 ACAP1 17 7240223 -0.81 0 0 6.027 0.630886
cg09298971 SLC44A4 6 31846249 -0.81 0 0 NA 0.612972
cg18581405 S1PR4 19 3180035 -0.81 0 0 4.358 0.669269
cg10402417 TBC1D10C 11 67171476 -0.8 0 0 5.803 0.668638
cg19353949 PDZK1 1 145726979 -0.8 0 0 6.469 0.634951
cg15700022 PP14571 2 241396251 -0.8 0 0 NA 0.597750
cg14058239 SLC39A6 18 33706228 -0.8 0 0 13.863 0.693817
cg07786657 CD247 1 167487633 -0.8 0 0 5.764 0.815991
cg21773162 ZAP70 2 98330087 -0.8 0 0 NA 0.681910
cg09781936 TBX1 22 19749961 -0.8 0 0 NA 0.716947
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/2008397/0.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/2008266/0.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.