Head and Neck 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 probes per gene are displayed. Total number of matched samples = 303. Number of gene expression samples = 303. Number of methylation samples = 303.

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 = 303

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
--- | --- | --- | --- | --- | --- | --- | --- | ---
cg12889195 | LOC654433 | 2 | 113992843 | -0.89 | 0 | 0 | 7.246 | 0.676573
cg12258179 | RASIP1 | 19 | 49232187 | -0.86 | 0 | 0 | 8.366 | 0.652176
cg03669949 | DDX43 | 6 | 74104426 | -0.86 | 0 | 0 | NA | 0.814899
cg12889195 | PAX8 | 2 | 113992843 | -0.85 | 0 | 0 | 5.831 | 0.676573
cg02423817 | PTPRCAP | 11 | 67203661 | -0.84 | 0 | 0 | 7.286 | 0.699887
cg05991820 | ECHDC3 | 10 | 11785161 | -0.83 | 0 | 0 | 6.264 | 0.587080
cg00292135 | C7orf13 | 7 | 156433068 | -0.82 | 0 | 0 | 5.890 | 0.269792
cg23659134 | GSTO2 | 10 | 106035168 | -0.82 | 0 | 0 | 6.494 | 0.580954
cg07590529 | TBX18 | 6 | 85471973 | -0.81 | 0 | 0 | NA | 0.538737
cg24040502 | NLRP2 | 19 | 55477810 | -0.81 | 0 | 0 | 6.185 | 0.710543
cg05363903 | IQCA1 | 2 | 237415899 | -0.81 | 0 | 0 | 5.674 | 0.523240
cg01070987 | PFN2 | 3 | 149687002 | -0.81 | 0 | 0 | 11.031 | 0.501508
cg21494776 | ICAM4 | 19 | 10397780 | -0.8 | 8.4e-68 | 6.9e-68 | 4.608 | 0.508474
cg02416424 | KRT19 | 17 | 39684825 | -0.79 | 0 | 0 | NA | 0.333556
cg12557114 | WISP3 | 6 | 112375870 | -0.79 | 0 | 0 | NA | 0.740931
cg10088332 | GTSF1 | 12 | 54867429 | -0.79 | 0 | 0 | NA | 0.835094
cg14299940 | PHYHD1 | 9 | 131684923 | -0.79 | 0 | 0 | 5.892 | 0.381474
cg14732998 | ZNF793 | 19 | 37997831 | -0.79 | 0 | 0 | NA | 0.313249
cg03555227 | RANBP17 | 5 | 170289070 | -0.79 | 0 | 0 | NA | 0.489940
cg01328500 | IQCG | 3 | 197639792 | -0.79 | 0 | 0 | 8.357 | 0.611469
cg04449108 | UGT1A6 | 2 | 234601254 | -0.78 | 0 | 0 | NA | 0.800742
cg10880599 | GPX2 | 14 | 65408480 | -0.78 | 0 | 0 | 9.782 | 0.617425
cg08250586 | DNAH17 | 17 | 76533316 | -0.78 | 0 | 0 | 8.279 | 0.628280
cg17105755 | C2orf65 | 2 | 74875317 | -0.77 | 0 | 0 | NA | 0.595198
cg26314750 | C15orf56 | 15 | 40545794 | -0.77 | 3.4e-52 | 2.8e-52 | NA | 0.527280
cg18233746 | MGST1 | 12 | 16500403 | -0.77 | 0 | 0 | 7.332 | NA

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_MethylationPreprocess/HNSC/2008550/0.GDAC_MethylationPreprocess.Finished/HNSC.meth.for_correlation.filtered_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/HNSC/2008416/0.mRNAseq_preprocessor.Finished/HNSC.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

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)

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