reproducibility and concordance of differential dna methylation and gene expression in cancer再现性和一致性差dna甲基化和基因表达的癌症.pdfVIP

Reproducibility and Concordance of Differential DNA Methylation and Gene Expression in Cancer 1 1 1 1 1 1,2 Chen Yao , Hongdong Li , Xiaopei Shen , Zheng He , Lang He , Zheng Guo * 1 Bioinformatics Centre and Key Laboratory for NeuroInfomation of the Education Ministry of China, School of Life Science, University of Electronic Science and Technology of China, Chengdu, China, 2 Colleges of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China Abstract Background: Hundreds of genes with differential DNA methylation of promoters have been identified for various cancers. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed. Methodology/Principal Findings: Using array data for seven types of cancers, we first evaluated the effects of experimental batches on differential DNA methylation detection. Second, we compared the directions of DNA methylation changes detected from different datasets for the same cancer. Third, we evaluated the concordance between methylation and gene expression changes. Finally, we compared DNA methylation changes in different cancers. For a given cancer, the directions of methylation and expression changes detected from different datasets, excluding potential batch effects, were highly consistent. In different cancers, DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression, whereas hypomethylation was only weakly correlated with the up-regulation of genes. Finally, we found that genes commonly hypomethylated in different cancers primarily