MethLAB: a graphical user interface package for the analysis of array-based DNA methylation data - PubMed (original) (raw)

MethLAB: a graphical user interface package for the analysis of array-based DNA methylation data

Varun Kilaru et al. Epigenetics. 2012 Mar.

Abstract

Recent evidence suggests that DNA methylation changes may underlie numerous complex traits and diseases. The advent of commercial, array-based methods to interrogate DNA methylation has led to a profusion of epigenetic studies in the literature. Array-based methods, such as the popular Illumina GoldenGate and Infinium platforms, estimate the proportion of DNA methylated at single-base resolution for thousands of CpG sites across the genome. These arrays generate enormous amounts of data, but few software resources exist for efficient and flexible analysis of these data. We developed a software package called MethLAB (http://genetics.emory.edu/conneely/MethLAB) using R, an open source statistical language that can be edited to suit the needs of the user. MethLAB features a graphical user interface (GUI) with a menu-driven format designed to efficiently read in and manipulate array-based methylation data in a user-friendly manner. MethLAB tests for association between methylation and relevant phenotypes by fitting a separate linear model for each CpG site. These models can incorporate both continuous and categorical phenotypes and covariates, as well as fixed or random batch or chip effects. MethLAB accounts for multiple testing by controlling the false discovery rate (FDR) at a user-specified level. Standard output includes a spreadsheet-ready text file and an array of publication-quality figures. Considering the growing interest in and availability of DNA methylation data, there is a great need for user-friendly open source analytical tools. With MethLAB, we present a timely resource that will allow users with no programming experience to implement flexible and powerful analyses of DNA methylation data.

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Figures

Figure 1

Figure 1

(A) A menu-driven Graphical User Interface (GUI) is used for loading methylation and phenotype files, selecting inclusion criteria and specifying the analytical model. (B) Analysis results are summarized in a spreadsheet-ready text file.

Figure 2

Figure 2

Manhattan plot of the negative log p values for each CpG site (vertical axis) by chromosome number and genomic position (horizontal axis). Dotted line indicates Holm significance.

Figure 3

Figure 3

Automated quantile-quantile (Q-Q) plots based on (A) negative log p values from analysis of methylation and TLS and (B) ordered t statistics from analysis of sex-differential methylation.

Figure 4

Figure 4

MethLAB automates (A) scatter or (B) box plots depicting methylation of specific CpG sites by continuous or categorical trait values. CpG probe and gene names are indicated in the plot titles.

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