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 probes per gene are displayed. Total number of matched samples = 92. Number of gene expression samples = 220. Number of methylation samples = 92.

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 = 92

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
--- | --- | --- | --- | --- | --- | --- | --- | ---
cg06797068 | DDX43 | 6 | 74161321 | -0.91 | 0 | 0 | NA | 0.673752
cg11763394 | PAX8 | 2 | 113709392 | -0.87 | 0 | 0 | 5.725 | 0.675711
cg21550016 | LOC654433 | 2 | 113709401 | -0.86 | 0 | 0 | 7.125 | 0.663300
cg06723057 | NUPR1 | 16 | 28457424 | -0.84 | 0 | 0 | 10.649 | 0.601055
cg00032205 | TSPYL5 | 8 | 98359548 | -0.84 | 0 | 0 | 9.120 | 0.321283
cg14115220 | CDH26 | 20 | 57966816 | -0.84 | 0 | 0 | 6.001 | 0.719731
cg08702413 | ALDH7A1 | 5 | 125959174 | -0.84 | 0 | 0 | 8.853 | 0.345447
cg14717314 | CLEC2L | 7 | 138877651 | -0.84 | 0 | 0 | NA | 0.738084
cg06454760 | ZNF135 | 19 | 63262239 | -0.83 | 0 | 0 | 5.494 | 0.513198
cg00141162 | HCLS1 | 3 | 122862467 | -0.83 | 0 | 0 | 10.164 | 0.442289
cg05508084 | ZNF667 | 19 | 61680210 | -0.82 | 0 | 0 | NA | 0.336686
cg22958090 | KRT7 | 12 | 50913705 | -0.82 | 0 | 0 | 9.908 | 0.649590
cg21493505 | ZNF542 | 19 | 61571230 | -0.82 | 0 | 0 | 7.043 | 0.433840
cg16996266 | ARTN | 1 | 44173455 | -0.81 | 0 | 0 | 7.504 | 0.622895
cg05991820 | ECHDC3 | 10 | 11825167 | -0.81 | 0 | 0 | 6.941 | 0.541776
cg13620881 | SYCP2L | 6 | 10996115 | -0.81 | 0 | 0 | NA | 0.737415
cg15374435 | SPRY2 | 13 | 79809693 | -0.81 | 0 | 0 | 9.003 | 0.628824
cg00275449 | ACAP2 | 3 | 196643416 | -0.81 | 0 | 0 | 11.198 | 0.205340
cg00357958 | GPR81 | 12 | 121780963 | -0.81 | 0 | 0 | NA | 0.442562
cg02731193 | GCLC | 6 | 53515145 | -0.81 | 0 | 0 | 11.565 | 0.634736
cg24169822 | HOXA4 | 7 | 27137519 | -0.8 | 0 | 0 | 5.866 | 0.419267
cg17388172 | TXNRD1 | 12 | 103211722 | -0.8 | 0 | 0 | 12.429 | 0.659637
cg19409149 | UGT1A9 | 2 | 234273108 | -0.8 | 0 | 0 | NA | 0.725824
cg19648686 | AKR1C2 | 10 | 5034992 | -0.8 | 0 | 0 | 12.109 | 0.758059
cg17286244 | SPESP1 | 15 | 67009646 | -0.8 | 0 | 0 | 4.186 | 0.549453
cg04983151 | ALS2CR11 | 2 | 202191949 | -0.79 | 0 | 0 | 3.096 | 0.754738

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/LUSC/1841531/0.GDAC_MethylationPreprocess.Finished/LUSC.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/LUSC/1768817/0.mRNAseq_preprocessor.Finished/LUSC.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)

Copyright © 2012 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
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