Correlation between mRNA expression and DNA methylation
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
Maintained by Richard Park (Boston University/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNA expression and DNA methylation. Broad Institute of MIT and Harvard. doi:10.7908/C1J38R8S
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 = 206. Number of gene expression samples = 206. Number of methylation samples = 256.

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 = 206

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
cg21550016 LOC654433 2 113992930 -0.92 0 0 5.9 0.76
cg02876237 ZNF614 19 52531528 -0.87 0 0 6.1 0.24
cg10263370 ZNF502 3 44754102 -0.86 0 0 4.6 0.37
cg02835214 ZNF134 19 58125672 -0.86 1.9e-62 1.6e-62 5.2 0.38
cg09643186 GPX2 14 65409452 -0.86 0 0 8 0.59
cg12950007 ZNF528 19 52900970 -0.86 2.8e-61 2.5e-61 5 0.47
cg25451874 ZNF569 19 37958444 -0.85 0 0 5.2 0.34
cg24415565 LOC148189 19 28284988 -0.85 0 0 3.6 0.29
cg10157975 ZNF304 19 57862442 -0.85 0 0 6.3 0.19
cg22731359 ZNF256 19 58459136 -0.84 0 0 4.7 0.32
cg24040502 NLRP2 19 55477810 -0.84 0 0 7.3 0.66
cg09260640 ZNF419 19 57999177 -0.84 0 0 5.7 0.4
cg24392574 CALML5 10 5541423 -0.84 0 0 8.5 0.72
cg13101072 FAM50B 6 3849818 -0.84 0 0 6.9 0.52
cg18649745 ZNF350 19 52490223 -0.83 0 0 5.9 0.36
cg01574481 REC8 14 24641852 -0.83 0 0 8.6 0.52
cg26827373 ZNF844 19 12175935 -0.83 0 0 4.6 0.45
cg26333652 IRX2 5 2750758 -0.83 0 0 5.3 0.56
cg07037032 AKR7A3 1 19614429 -0.83 0 0 5.7 0.6
cg17853707 ZNF91 19 23578260 -0.82 1.9e-52 1.7e-52 5.8 0.39
cg14038484 ZNF586 19 58281450 -0.82 0 0 6.4 0.37
cg04181321 ZNF71 19 57106852 -0.82 0 0 6.5 0.22
cg25963041 ZFP28 19 57049777 -0.82 0 0 4.5 0.53
cg14732998 ZNF793 19 37997831 -0.82 0 0 5 0.37
cg15167155 ZNF347 19 53662499 -0.82 0 0 4.8 0.34
cg01070987 PFN2 3 149687002 -0.82 0 0 11 0.51
Methods & Data
Input

Methylation Array Platforms: Illumina Infinium HumanMethylation27, Illumina Infinium HumanMethylation450, Illumina DNA Methylation OMA002, Illumina DNA Methylation OMA003

  • methylation file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MethylationPreprocess/CESC-TP/9831248/CESC-TP.meth.by_min_expr_corr.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/CESC-TP/9829538/CESC-TP.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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.