Lung Squamous Cell Carcinoma: 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 = 133 Number of gene expression samples = 135 Number of methylation samples = 154

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 = 133

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
cg16363586 BST2 19 17377329 -0.84 0 0 -0.8874439 0.48355
cg09645888 ME3 11 86061233 -0.82 0 0 0.0051216 0.40868
cg08124399 DDX43 6 74161589 -0.82 0 0 -1.0279354 0.74000
cg08675664 ALDH7A1 5 125958769 -0.81 0 0 -1.5902249 0.35307
cg23234999 MKRN3 15 21362298 -0.81 0 0 -0.8898628 0.62861
cg03969797 MKRN3 15 21361757 -0.8 0 0 -0.8898628 0.37347
cg22497867 MAGEA4 X 150831952 -0.78 0 0 0.1375771 0.71874
cg24169822 HOXA4 7 27137519 -0.78 0 0 -0.1329204 0.50109
cg05740244 LDHC 11 18390591 -0.78 0 0 -0.5669073 NA
cg14654875 ZNF597 16 3433998 -0.78 0 0 -0.0457094 0.51798
cg17188169 DDX43 6 74161109 -0.78 0 0 -1.0279354 0.72426
cg00186701 TSPYL5 8 98359686 -0.77 0 0 1.9912330 0.32647
cg15149645 NUPR1 16 28458120 -0.77 0 0 1.5690746 0.54608
cg00141162 HCLS1 3 122862467 -0.77 0 0 0.8591347 0.36871
cg13500819 MGC29506 5 138753299 -0.76 0 0 -1.0631150 0.74419
cg10146929 HIST1H1A 6 26125918 -0.76 0 0 0.9598879 0.45525
cg05590982 NUPR1 16 28457672 -0.76 0 0 1.5690746 0.42645
cg13702536 GPR81 12 121781506 -0.75 0 0 -1.0087124 0.57121
cg15747595 TSPYL5 8 98359056 -0.75 0 0 1.9912330 0.40308
cg06392589 IL20RB 3 138159536 -0.75 0 0 1.8418841 0.60927
cg13448625 COL17A1 10 105835228 -0.75 0 0 2.0496300 0.58250
cg15518883 SIT1 9 35640561 -0.74 0 0 0.2744017 0.76304
cg04759756 SLA2 20 34707347 -0.74 0 0 -0.1929962 0.83468
cg07560096 ME3 11 86060830 -0.74 0 0 0.0051216 0.31645
cg18738906 SCNN1A 12 6354000 -0.74 0 0 0.9667701 0.73460
cg13840968 CIDEB 14 23850766 -0.74 0 0 -0.2048546 0.54818
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/LUSC/1444678/2.GDAC_MergeDataFiles.Finished/LUSC.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/LUSC/1456653/0.GDAC_mRNA_Preprocess_Median.Finished/LUSC.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.