Breast Invasive 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 = 313 Number of gene expression samples = 315 Number of methylation samples = 529

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 = 313

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
--- | --- | --- | --- | --- | --- | --- | --- | ---
cg15518883 | SIT1 | 9 | 35640561 | -0.87 | 0 | 0 | -0.7561113 | 0.79834
cg24674703 | CD5 | 11 | 60626536 | -0.85 | 0 | 0 | -0.5527233 | 0.81111
cg05740244 | LDHC | 11 | 18390591 | -0.81 | 0 | 0 | -0.3648352 | NA
cg10045881 | CHI3L2 | 1 | 111571814 | -0.77 | 0 | 0 | 0.0124000 | 0.47735
cg11584936 | BNIPL | 1 | 149276212 | -0.76 | 0 | 0 | 1.9432771 | 0.31436
cg20792833 | PTPRCAP | 11 | 66961771 | -0.75 | 0 | 0 | 0.0114289 | 0.74647
cg11600161 | TBC1D10C | 11 | 66928161 | -0.75 | 0 | 0 | -0.6209401 | 0.74113
cg00083937 | MAPK8IP2 | 22 | 49386671 | -0.75 | 0 | 0 | 1.1637207 | 0.50123
cg09886641 | SPESP1 | 15 | 67010072 | -0.75 | 0 | 0 | -0.5436779 | 0.72216
cg07347645 | SYCP2 | 20 | 57940566 | -0.74 | 0 | 0 | 0.4869331 | 0.49812
cg24392574 | CALML5 | 10 | 5531423 | -0.74 | 0 | 0 | 0.5831059 | 0.85288
cg03534410 | TMEM40 | 3 | 12776112 | -0.74 | 0 | 0 | 0.9705535 | 0.58606
cg16363586 | BST2 | 19 | 17377329 | -0.74 | 0 | 0 | 0.2386330 | 0.38628
cg18738906 | SCNN1A | 12 | 6354000 | -0.74 | 0 | 0 | 1.5662966 | 0.65984
cg24841244 | CD3D | 11 | 117718540 | -0.74 | 0 | 0 | -2.7889074 | 0.75124
cg22214414 | SYCP2 | 20 | 57940627 | -0.74 | 0 | 0 | 0.4869331 | 0.54263
cg09522147 | KRT7 | 12 | 50913609 | -0.73 | 0 | 0 | 1.6906236 | 0.41286
cg22266967 | S100P | 4 | 6746599 | -0.73 | 0 | 0 | -0.8492340 | 0.53830
cg09902130 | CD6 | 11 | 60495754 | -0.73 | 0 | 0 | 0.1282934 | 0.81545
cg17078393 | LCK | 1 | 32489589 | -0.73 | 0 | 0 | -1.9460200 | 0.77514
cg00328227 | C1orf59 | 1 | 109005848 | -0.72 | 0 | 0 | -0.3326757 | 0.37410
cg24926276 | LRG1 | 19 | 4490943 | -0.72 | 0 | 0 | 0.6726182 | 0.37479
cg13840968 | CIDEB | 14 | 23850766 | -0.72 | 0 | 0 | 0.0568538 | 0.59526
cg05982504 | IGFALS | 16 | 1784963 | -0.72 | 0 | 0 | 1.5367276 | 0.53999
cg04759756 | SLA2 | 20 | 34707347 | -0.72 | 0 | 0 | -0.2421877 | 0.83782
cg10590292 | BIN2 | 12 | 50003941 | -0.72 | 0 | 0 | -0.0801965 | 0.75401

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/BRCA/1444363/2.GDAC_MergeDataFiles.Finished/BRCA.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/BRCA/1456397/0.GDAC_mRNA_Preprocess_Median.Finished/BRCA.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)

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