a statistical method for excluding non-variable cpg sites in high-throughput dna methylation profiling统计方法包括不变cpg网站高通量dna甲基化分析.pdfVIP

Meng et al. BMC Bioinformatics 2010, 11:227 /1471-2105/11/227 M E T H O D O L O G Y A R T I C L E Open Access Methodology article A statistical method for excluding non-variable CpG sites in high-throughput DNA methylation profiling 1,4 2 3 1 1 1,5 1,6 Hailong Meng* , Andrew R Joyce , Daniel E Adkins , Priyadarshi Basu , Yankai Jia , Guoya Li , Tapas K Sengupta , 2 2 3 Barbara K Zedler , E Lenn Murrelle and Edwin JCG van den Oord Abstract Background: High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called non-variable sites will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers. Results: We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation. Conclusions: Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level. Back