Thyroid 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 probes per gene are displayed. Total number of matched samples = 254. Number of gene expression samples = 254. Number of methylation samples = 254.

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 = 254

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
--- | --- | --- | --- | --- | --- | --- | --- | ---
cg21188037 | MYO1G | 7 | 45018658 | -0.91 | 0 | 0 | 8.093 | 0.569148
cg24749672 | BIN2 | 12 | 51718108 | -0.88 | 0 | 0 | 6.204 | 0.883046
cg25571414 | SLC34A2 | 4 | 25659572 | -0.87 | 0 | 0 | 13.742 | 0.615451
cg21163717 | DOK2 | 8 | 21769903 | -0.87 | 0 | 0 | 6.096 | 0.819406
cg16983159 | TMEM173 | 5 | 138862441 | -0.87 | 0 | 0 | 10.017 | 0.386395
cg11763394 | LOC654433 | 2 | 113992921 | -0.87 | 0 | 0 | 4.146 | 0.905623
cg08480068 | SPN | 16 | 29674959 | -0.86 | 0 | 0 | 6.827 | 0.903044
cg27398499 | TACSTD2 | 1 | 59043873 | -0.85 | 0 | 0 | 11.480 | 0.424629
cg07641284 | C16orf54 | 16 | 29756951 | -0.85 | 0 | 0 | 4.462 | 0.835537
cg07150145 | PDZK1IP1 | 1 | 47656137 | -0.85 | 0 | 0 | NA | 0.365997
cg22502856 | LAMB3 | 1 | 209825678 | -0.85 | 0 | 0 | 10.411 | 0.732651
cg26648103 | SYT12 | 11 | 66791718 | -0.85 | 9.6e-72 | 6.3e-72 | 8.450 | 0.409266
cg18738906 | SCNN1A | 12 | 6483739 | -0.84 | 0 | 0 | 11.292 | 0.709130
cg15761609 | FAM20A | 17 | 66598067 | -0.84 | 0 | 0 | 9.721 | 0.338527
cg18157738 | IGFN1 | 1 | 201161205 | -0.84 | 0 | 0 | NA | 0.784526
cg11787522 | STRA6 | 15 | 74495109 | -0.83 | 0 | 0 | 7.315 | 0.466392
cg25651476 | NLRP2 | 19 | 55476717 | -0.83 | 0 | 0 | NA | 0.554038
cg09032544 | CD247 | 1 | 167487295 | -0.83 | 0 | 0 | 5.101 | 0.926739
cg26230275 | S100A10 | 1 | 151965283 | -0.83 | 0 | 0 | 10.676 | 0.542049
cg08686960 | COX7A1 | 19 | 36642720 | -0.83 | 0 | 0 | 7.538 | 0.579497
cg05564251 | SP140 | 2 | 231090640 | -0.83 | 0 | 0 | 4.511 | 0.840878
cg07675031 | SPI1 | 11 | 47399893 | -0.83 | 0 | 0 | 7.798 | 0.909336
cg25754958 | PTPN7 | 1 | 202130692 | -0.83 | 0 | 0 | 5.741 | 0.767062
cg06799735 | AHNAK2 | 14 | 105437141 | -0.82 | 0 | 0 | 9.947 | 0.618610
cg10397389 | DAPP1 | 4 | 100738011 | -0.82 | 0 | 0 | 4.671 | 0.813744
cg09906448 | LY6G6C | 6 | 31688160 | -0.82 | 0 | 0 | NA | 0.519257

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/THCA/2009188/0.GDAC_MethylationPreprocess.Finished/THCA.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/THCA/2008957/0.mRNAseq_preprocessor.Finished/THCA.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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