Detecting Differentially Methylated Loci for Multiple Treatments Based on High-Throughput Methylation Data

Chen, Zhongxue
Huang, Hanwen
Liu, Qingzhong
Journal Title
Journal ISSN
Volume Title
BMC Bioinformatics

Background: Because of its important effects, as an epigenetic factor, on gene expression and disease development, DNA methylation has drawn much attention from researchers. Detecting differentially methylated loci is an important but challenging step in studying the regulatory roles of DNA methylation in a broad range of biological processes and diseases. Several statistical approaches have been proposed to detect significant methylated loci; however, most of them were designed specifically for case-control studies. Results: Noticing that the age is associated with methylation level and the methylation data are not normally distributed, in this paper, we propose a nonparametric method to detect differentially methylated loci under multiple conditions with trend for Illumina Array Methylation data. The nonparametric method, Cuzick test is used to detect the differences among treatment groups with trend for each age group; then an overall p-value is calculated based on the method of combining those independent p-values each from one age group. Conclusions: We compare the new approach with other methods using simulated and real data. Our study shows that the proposed method outperforms other methods considered in this paper in term of power: it detected more biological meaningful differentially methylated loci than others.

This article was originally published by BMC Bioinformatics
Cuzick test, nonpragmatic test, trend test
Chen et al.: Detecting differentially methylated loci for multiple treatments based on high-throughput methylation data. BMC Bioinformatics 2014 15:142. doi:10.1186/1471-2105-15-142