Introduction

| Recently, many studies suggest that enhancers play a major role as regulators of cell-specific phenotypes leading to alteration in transcriptomes realated to diseases . In order to investigate regulatory enhancers that can be located at long distances upstream or downstream of target genes Bioconductor offer the Enhancer Linking by Methylation/Expression Relationship (ELMER) package. This package is designed to combine DNA methylation and gene expression data from human tissues to infer multi-level cis-regulatory networks. It uses DNA methylation to identify enhancers and correlates their state with expression of nearby genes to identify one or more transcriptional targets. Transcription factor (TF) binding site analysis of enhancers is coupled with expression analysis of all TFs to infer upstream regulators.

Input

As input ELMER uses a specific R obeject called mee which contains a matrix of DNA methylation from HM450K platform for multiple samples; a matrix of gene expression for the same samples; a GRanges object containing the information for probes on HM450K such as names and coordinates; a gene annotation which is also a GRanges object.

ELMER steps

Step 1 | Identify distal enhancer probes on HM450K.
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Step 2 | Identify distal enhancer probes with significantly different DNA methyaltion level in control group and experiment group.
Step 3 | Identify putative target genes for differentially methylated distal enhancer probes.
Step 4 | Identify enriched motifs for the distal enhancer probes which are significantly differentially methylated and linked to putative target gene.
Step 5 | Identify regulatory TFs whose expression associate with DNA methylation at motifs.