Correlation between mRNA expression and DNA methylation
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
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/C1J10223
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 = 225. Number of gene expression samples = 289. Number of methylation samples = 226.

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 = 225

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
cg02640604 QPRT 16 29690271 -0.88 0 0 9.4 0.5
cg11763394 LOC654433 2 113992921 -0.88 0 0 4 0.89
cg05981038 CARD6 5 40841590 -0.88 0 0 7.3 0.54
cg07786657 CD247 1 167487633 -0.87 0 0 5.6 0.87
cg16983159 TMEM173 5 138862441 -0.86 0 0 8 0.62
cg25520422 GRM5 11 88240817 -0.86 0 0 6.2 0.54
cg27102649 SERPINF1 17 1665172 -0.86 0 0 9.4 0.75
cg24040502 NLRP2 19 55477810 -0.86 0 0 4.4 0.73
cg09307985 COX7A1 19 36643070 -0.86 0 0 6.2 0.79
cg21987921 LOC100130872 4 1198478 -0.85 0 0 6.6 0.66
cg14506696 DAPP1 4 100737830 -0.85 0 0 5.1 0.65
cg19145218 C20orf54 20 749336 -0.84 0 0 4.7 0.53
cg20092122 BST2 19 17517221 -0.84 0 0 9 0.6
cg07013680 SPTBN5 15 42186124 -0.84 0 0 6.2 0.57
cg26034919 KRTCAP3 2 27665711 -0.83 0 0 5.4 0.6
cg10096378 FAM83F 22 40391617 -0.83 0 0 4 0.59
cg14467840 S100A1 1 153600972 -0.83 0 0 9.7 0.62
cg22958090 KRT7 12 52627438 -0.83 0 0 12 0.41
cg17836145 VNN2 6 133084642 -0.83 0 0 5.9 0.43
cg21773633 WISP3 6 112375324 -0.83 0 0 3.9 0.61
cg10633838 B3GALT4 6 33245359 -0.83 0 0 7.2 0.32
cg09298971 SLC44A4 6 31846249 -0.83 0 0 11 0.53
cg20693209 SPON1 11 13984067 -0.83 0 0 11 0.25
cg16048383 SCNN1A 12 6483708 -0.82 0 0 12 0.57
cg16068833 CD52 1 26644515 -0.82 0 0 7.8 0.74
cg14654385 FERMT3 11 63973006 -0.82 0 0 8.5 0.77
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/KIRP-TP/11493886/KIRP-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/KIRP-TP/11493511/KIRP-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.