Correlation between mRNA expression and DNA methylation
Cholangiocarcinoma (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/C1BR8RJ2
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 = 36. Number of gene expression samples = 36. Number of methylation samples = 36.

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 = 36

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
cg04511534 GGT6 17 4463371 -0.94 0 0 6.7 0.68
cg17275162 ASGR2 17 7017785 -0.91 0 0 10 0.61
cg05989861 PROM2 2 95940031 -0.9 0 0 8.1 0.66
cg06907626 NPC1L1 7 44580809 -0.9 0 0 8.9 0.58
cg03209642 FES 15 91427605 -0.88 0 0 8.1 0.37
cg12889195 PAX8 2 113992843 -0.87 0 0 7.2 0.68
cg23245485 SCNN1A 12 6484219 -0.87 0 0 9.2 0.62
cg17771150 LCP1 13 46756209 -0.86 1.6e-08 3.6e-06 11 0.67
cg12950007 ZNF528 19 52900970 -0.85 2.2e-08 4.1e-06 7.4 0.25
cg07948194 SLC30A10 1 220099770 -0.85 6.2e-08 4.2e-06 7.8 0.56
cg17044311 ABCC2 10 101542983 -0.85 2.5e-08 4.1e-06 7.1 0.73
cg11011913 TM4SF18 3 149051159 -0.85 2.8e-08 4.1e-06 6.3 0.73
cg26656452 HABP2 10 115313165 -0.85 2.8e-08 4.1e-06 12 0.56
cg08450017 CXCR6 3 45984838 -0.85 3e-08 4.1e-06 5.1 0.77
cg15518883 SIT1 9 35650561 -0.85 3.2e-08 4.1e-06 4.1 0.84
cg11758345 TMEM105 17 79304498 -0.85 3.7e-08 4.1e-06 4.5 0.68
cg07274998 OAT 10 126107781 -0.85 3.7e-08 4.1e-06 9 0.27
cg05036173 SULT1C4 2 108994528 -0.85 3.9e-08 4.1e-06 6.2 0.51
cg02531794 SRCRB4D 7 76039208 -0.85 4.1e-08 4.1e-06 5.8 0.71
cg07868155 CXCL5 4 74864709 -0.85 4.3e-08 4.1e-06 7 0.7
cg26806924 PROCR 20 33760017 -0.84 5.1e-08 4.1e-06 8 0.48
cg25320780 SLC16A4 1 110933345 -0.84 5.3e-08 4.1e-06 6.9 0.59
cg19982230 RAB34 17 27045302 -0.84 5.3e-08 4.1e-06 9.9 0.32
cg09257332 ZFP82 19 36909913 -0.84 5.4e-08 4.1e-06 4.5 0.29
cg25520422 GRM5 11 88240817 -0.84 2.7e-07 5e-06 5.2 0.58
cg10841756 PVRL4 1 161059267 -0.84 5.5e-08 4.1e-06 8.7 0.52
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/CHOL-TP/22316714/CHOL-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/CHOL-TP/22312688/CHOL-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.