Lung Adenocarcinoma: 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 probe(s) per gene are displayed. Total number of matched samples = 31 Number of gene expression samples = 129 Number of methylation samples = 32

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 = 31

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 probe(s) per gene. Correlation Coefficient: See Methods & Data below. Expression Mean and Expression Variance: median and variance of gene expression levels of gene expression probes associated with the gene. Methylation Mean and Methylation Variance: median and variance of methylation levels of CpG methylation probes associated with the gene.

Meth_Probe | Gene | Chrom | Position | Corr_Spearman | Pval_Spearman | Qval | Expr_Mean | Meth_Mean
--- | --- | --- | --- | --- | --- | --- | --- | ---
cg03699566 | FOLR1 | 11 | 71578300 | -0.8 | 9.3e-07 | 0.0063 | 4.711e-01 | 0.48833
cg14385738 | PTPN22 | 1 | 114215863 | -0.77 | 1.6e-06 | 0.0063 | 7.068e-01 | 0.38786
cg27420236 | RPRM | 2 | 154042962 | -0.77 | 1.6e-06 | 0.0063 | -1.358e+00 | 0.16821
cg04457794 | CTSE | 1 | 204484277 | -0.77 | 1.8e-06 | 0.0063 | 4.277e+00 | 0.48242
cg00916635 | PTPN22 | 1 | 114215835 | -0.77 | 1.8e-06 | 0.0063 | 7.068e-01 | 0.44184
cg09643186 | GPX2 | 14 | 64479205 | -0.76 | 2.4e-06 | 0.0067 | -9.383e-01 | 0.74874
cg14494812 | TOB1 | 17 | 46296038 | -0.75 | 2.7e-06 | 0.0067 | -1.269e-01 | 0.65087
cg21478437 | CTSE | 1 | 204484026 | -0.74 | 4e-06 | 0.0088 | 4.277e+00 | 0.49805
cg18846362 | CA12 | 15 | 61461212 | -0.74 | 5.3e-06 | 0.01 | -1.350e+00 | 0.06549
cg11070419 | C4BPA | 1 | 205343833 | -0.73 | 7.4e-06 | 0.013 | 3.915e+00 | 0.47466
cg22387994 | NAPA | 19 | 52710012 | -0.72 | 8.8e-06 | 0.014 | -1.589e-01 | 0.06677
cg27246571 | HAL | 12 | 94913719 | -0.72 | 0.000011 | 0.016 | -9.156e-02 | 0.77007
cg02659086 | GSTP1 | 11 | 67107552 | -0.7 | 0.000018 | 0.023 | 6.058e-01 | 0.07746
cg05564251 | SP140 | 2 | 230798884 | -0.7 | 0.000018 | 0.023 | 1.334e+00 | 0.69082
cg19786920 | NSUN7 | 4 | 40446527 | -0.7 | 0.000022 | 0.023 | 1.153e+00 | 0.14716
cg21750589 | ZNF323 | 6 | 28429280 | -0.7 | 0.000022 | 0.023 | 2.037e+00 | 0.43756
cg10055471 | NR0B2 | 1 | 27112906 | -0.7 | 0.000022 | 0.023 | -2.203e+00 | 0.83400
cg01356829 | IL12RB2 | 1 | 67545484 | -0.7 | 0.000023 | 0.023 | 8.304e-01 | 0.47320
cg06172871 | HP | 16 | 70645745 | -0.69 | 0.000026 | 0.023 | 3.943e-01 | 0.60685
cg24713204 | ZNF471 | 19 | 61711185 | -0.69 | 0.000029 | 0.023 | 4.264e-01 | 0.41494
cg11787522 | STRA6 | 15 | 72282162 | -0.69 | 3e-05 | 0.023 | -2.953e-01 | 0.39218
cg02671171 | RPH3AL | 17 | 203087 | -0.69 | 3e-05 | 0.023 | 1.902e+00 | 0.39004
cg14289985 | ZNF471 | 19 | 61710660 | -0.69 | 0.000031 | 0.023 | 4.264e-01 | 0.26446
cg01991383 | FOXRED1 | 11 | 125644217 | -0.69 | 0.000031 | 0.023 | -1.630e+00 | 0.04503
cg22266967 | S100P | 4 | 6746599 | -0.69 | 0.000033 | 0.023 | -4.666e-02 | 0.59150
cg04513422 | C13orf29 | 13 | 110320315 | -0.68 | 0.000045 | 0.03 | 1.195e+00 | 0.25883

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_MergeDataFilesPipeline/LUAD/1269717/2.GDAC_MergeDataFiles.Finished/LUAD.methylation__humanmethylation27__jhu_usc_edu__Level_3__within_bioassay_data_set_function__data.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/GDAC_mRNA_Preprocess_Median/LUAD/1271088/0.GDAC_mRNA_Preprocess_Median.Finished/LUAD.medianexp.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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

Meta

- Maintainer = Richard Park

Copyright © 2011 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
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