Correlation between mRNA expression and DNA methylation
Kidney Renal Clear Cell Carcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
Maintained by Richard Park (Boston University/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between mRNA expression and DNA methylation. Broad Institute of MIT and Harvard. doi:10.7908/C1RR1XNJ
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 = 318. Number of gene expression samples = 533. Number of methylation samples = 319.

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 = 318

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
cg17188169 DDX43 6 74104388 -0.85 0 0 2.8 0.7
cg18653451 CCDC8 19 46917018 -0.85 0 0 7.5 0.32
cg21550016 LOC654433 2 113992930 -0.84 0 0 5.5 0.82
cg13234544 CCDC146 7 76911877 -0.82 0 0 9.4 0.8
cg21583694 TGFBI 5 135365401 -0.81 0 0 14 0.7
cg13714749 FAM83F 22 40391489 -0.81 3.7e-61 2e-61 3.5 0.63
cg08450017 CXCR6 3 45984838 -0.8 0 0 6.8 0.77
cg12792363 LGALS12 11 63274030 -0.79 1.2e-68 6.5e-69 4.6 0.68
cg15518883 SIT1 9 35650561 -0.79 0 0 5.9 0.77
cg25258033 RNASET2 6 167368657 -0.79 0 0 12 0.54
cg12705353 WDR66 12 122356852 -0.77 0 0 6.1 0.5
cg06532379 ALPK3 15 85360319 -0.77 0 0 9.8 0.45
cg09419670 LOC253039 9 123605666 -0.76 0 0 8.2 0.26
cg05564251 SP140 2 231090640 -0.76 0 0 6.1 0.79
cg14580211 C5orf62 5 150161299 -0.76 0 0 10 0.69
cg12472603 MXRA7 17 74705806 -0.75 0 0 12 0.73
cg12044599 PTPRCAP 11 67206308 -0.75 0 0 7.9 0.83
cg00939684 TMEM204 16 1599150 -0.75 0 0 9.8 0.63
cg18428193 KRTCAP3 2 27665017 -0.75 0 0 5.9 0.72
cg00903584 PTPN7 1 202128682 -0.75 0 0 7.5 0.7
cg09298971 SLC44A4 6 31846249 -0.74 0 0 7.8 0.76
cg16927606 TMEM149 19 36233324 -0.74 0 0 7.4 0.65
cg22208304 MOCOS 18 33768496 -0.74 7.4e-57 4.1e-57 5.2 0.8
cg03952543 FABP7 6 123101437 -0.74 0 0 9.5 0.6
cg25391117 C1QTNF3 5 34043284 -0.74 0 0 8.2 0.64
cg07383757 TRPC2 11 3647654 -0.74 0 0 3 0.5
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/KIRC-TP/22316762/KIRC-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/KIRC-TP/22312814/KIRC-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.