1 Introduction

This document provides an introduction of the ELMER.data, which contains supporting data for ELMER (Yao, L., Shen, H., Laird, P. W., Farnham, P. J., & Berman, B. P. 2015). ELMER is package using DNA methylation to identify enhancers, and correlates enhancer 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. ELMER.data provide 3 necessary data for ELMER analysis:

  1. Probes information: files with DNA methylation platforms metadata retrieved from http://zwdzwd.github.io/InfiniumAnnotation (Zhou, Wanding and Laird, Peter W and Shen, Hui 2016).
  2. Probes.motif: motif occurences within \(\pm 250bp\) of probe sites on HM450K/EPIC array aligned against hg19/hg38.

1.1 Installing and loading ELMER.data

To install this package, start R and enter

2 Contents

2.1 ENSEMBL gene and TSS information

Data from GRCh38.p12 and GRCh37.p13 accessed via biomart.

getTranscripts <- function(genome = "hg38"){
  
  tries <- 0L
  msg <- character()
  while (tries < 3L) {
    tss <- tryCatch({
      host <- ifelse(genome == "hg19",  "grch37.ensembl.org","www.ensembl.org")
      message("Accessing ", host, " to get TSS information")
      
      ensembl <- tryCatch({
        useEnsembl("ensembl", dataset = "hsapiens_gene_ensembl", host =  host)
      },  error = function(e) {
        message(e)
        for(mirror in c("asia","useast","uswest")){
          x <- useEnsembl("ensembl",
                          dataset = "hsapiens_gene_ensembl",
                          mirror = mirror,
                          host =  host)
          if(class(x) == "Mart") {
            return(x)
          }
        }
        return(NULL)
      })
      
      if(is.null(host)) {
        message("Problems accessing ensembl database")
        return(NULL)
      }
      attributes <- c("chromosome_name",
                      "start_position",
                      "end_position", "strand",
                      "ensembl_gene_id", 
                      "transcription_start_site",
                      "transcript_start",
                      "ensembl_transcript_id",
                      "transcript_end",
                      "external_gene_name")
      chrom <- c(1:22, "X", "Y","M","*")
      db.datasets <- listDatasets(ensembl)
      description <- db.datasets[db.datasets$dataset=="hsapiens_gene_ensembl",]$description
      message(paste0("Downloading transcripts information from ", ensembl@host, ". Using: ", description))
      
      filename <-  paste0(gsub("[[:punct:]]| ", "_",description),"_tss.rda")
      tss <- getBM(attributes = attributes, filters = c("chromosome_name"), values = list(chrom), mart = ensembl)
      tss <- tss[!duplicated(tss$ensembl_transcript_id),]
      save(tss, file = filename, compress = "xz")
    })
  }
  return(tss)
}

getGenes <- function (genome = "hg19"){
  tries <- 0L
  msg <- character()
  while (tries < 3L) {
    gene.location <- tryCatch({
      host <- ifelse(genome == "hg19", "grch37.ensembl.org", 
                     "www.ensembl.org")
      message("Accessing ", host, " to get gene information")
      ensembl <- tryCatch({
        useEnsembl("ensembl", dataset = "hsapiens_gene_ensembl", 
                   host = host)
      }, error = function(e) {
        message(e)
        for (mirror in c("asia", "useast", "uswest")) {
          x <- useEnsembl("ensembl", dataset = "hsapiens_gene_ensembl", 
                          mirror = mirror, host = host)
          if (class(x) == "Mart") {
            return(x)
          }
        }
        return(NULL)
      })
      if (is.null(host)) {
        message("Problems accessing ensembl database")
        return(NULL)
      }
      attributes <- c("chromosome_name", "start_position", 
                      "end_position", "strand", "ensembl_gene_id", 
                      "entrezgene", "external_gene_name")
      db.datasets <- listDatasets(ensembl)
      description <- db.datasets[db.datasets$dataset == 
                                   "hsapiens_gene_ensembl", ]$description
      message(paste0("Downloading genome information (try:", 
                     tries, ") Using: ", description))
      filename <- paste0(gsub("[[:punct:]]| ", "_", description), 
                         ".rda")
      if (!file.exists(filename)) {
        chrom <- c(1:22, "X", "Y")
        gene.location <- getBM(attributes = attributes, 
                               filters = c("chromosome_name"), values = list(chrom), 
                               mart = ensembl)
      }
      gene.location
    }, error = function(e) {
      msg <<- conditionMessage(e)
      tries <<- tries + 1L
    })
    if (!is.null(gene.location)) break
  }
  if (tries == 3L) 
    stop("failed to get URL after 3 tries:", "\n  error: ", msg)
  
  return(gene.location)
}

Human_genes__GRCh37_p13__tss <- getTranscripts(genome = "hg19")
Human_genes__GRCh38_p12__tss <- getTranscripts(genome = "hg38")
Human_genes__GRCh37_p13 <- getGenes("hg19")
Human_genes__GRCh38_p12 <- getGenes("hg38")
save(Human_genes__GRCh37_p13__tss,
     file = "Human_genes__GRCh37_p13__tss.rda", 
     compress = "xz")
     
save(Human_genes__GRCh38_p12,
     file = "Human_genes__GRCh38_p12.rda", 
     compress = "xz")
     
save(Human_genes__GRCh38_p12__tss,
     file = "Human_genes__GRCh38_p12__tss.rda", 
     compress = "xz")
     
save(Human_genes__GRCh37_p13,
     file = "Human_genes__GRCh37_p13.rda", 
     compress = "xz")

2.2 Probes information

Probes information were retrieved from http://zwdzwd.github.io/InfiniumAnnotation (Zhou, Wanding and Laird, Peter W and Shen, Hui 2016).