R/add_ensemble_regulatory.R

In isglobal-brge/epimutacions: Robust outlier identification for DNA methylation data

#' @title Add ENSEMBL regulatory regions to epimutations
#' 
#' @param epimutations a data frame object containing 
#' the result from \code{epimutations}
#' or \code{epimutations_one_leave_out} functions. 
#' @param build the build used to define epimutations coordinates. 
#' By default, it is \code{'37'},
#' corresponding to Illumina annotation.
#' 
#' @return The function returns a data frame object
#' containing the results of  \code{epimutations} 
#' or \code{epimutations_one_leave_out}
#' with some additional variables describing regulatory
#' elements from ENSEMBL. 
#' 
#' Note that a single epimutation might overlap with more than one
#' regulatory region. 
#' In that case, the different regulatory regions are separated by `///`.
#' \itemize{
#'  \item{ensembl_reg_id}{Region identifier from ENSEMBL}
#'  \item{ensembl_reg_coordinates}{Coordinates for 
#'  the ENSEMBL regulatory regions}
#'  \item{ensembl_reg_type}{Type of regulatory region}
#'  \item{ensembl_reg_tissues}{Activity of the regulatory 
#'  region per tissue. The different
#'  activation states are separated by `/`}
#' }
#' 
#' @importFrom biomaRt useEnsembl useDataset
#'
add_ensemble_regulatory <- function(epimutations,  build = "37")
{
    ## Remove chr from chromosome
    epimutations$chromosome <- gsub("chr", "", epimutations$chromosome)
    ## Create connection to ENSEMBL
    
    mart <- biomaRt::useEnsembl(biomart = "regulation",
                                GRCh = build)
    ensembl <- biomaRt::useDataset(dataset = "hsapiens_regulatory_feature",
                                    mart = mart)
    
    reg_res <- lapply(seq_len(nrow(epimutations)), function(i) {
        get_ENSEMBL_data( epimutations[i, "chromosome"],
                        epimutations[i, "start"],
                        epimutations[i, "end"],
                        mart = ensembl)
    })
    
    reg_res_df <- Reduce(rbind, reg_res)
    cbind(epimutations, reg_res_df)

}

#' Get ENSEMBL regulatory features overlapping a genomic region
#' 
#' This function queries for ENSEMBL regulatory 
#' features and collapse them to return
#' a single record.
#' 
#' @param chromosome Chromosome of the region
#' @param start Start of the region
#' @param end End of the region
#' @param mart \code{Mart} object to perform the ENSEMBL query
#' @importFrom biomaRt getBM
#' @return `data.frame` of one row with the ENSEMBL regulatory 
#' regions overlapping the genomic coordinate.
get_ENSEMBL_data <- function(chromosome, start, end, mart)
{
    bm <- biomaRt::getBM( attributes = c( "activity", "regulatory_stable_id",
                            "chromosome_name", "chromosome_start", 
                            "chromosome_end", "feature_type_name", 
                            "epigenome_name" ),
                        filters = c('chromosome_name', 'start', 'end'),
                        values = list(chromosome, start, end),
                        mart = mart )
    
    out_ens <- process_ENSEMBL_results(bm)
    out_ens
}

#' Process data from ENSEMBL 
#' 
#' Process data from ENSEMBL to combine results 
#' from the same regulatory elements in a unique record.
#' 
#' @param ensembl_res Results from `biomaRt::getBM`
#' @return `data.frame` of one row after collapsing 
#' the input ENSEMBL regulatory regions 
process_ENSEMBL_results <- function(ensembl_res)
{

    reg_elements <- unique(ensembl_res$regulatory_stable_id)
    
    reg_vals <- lapply(reg_elements, function(i) {
            merge_records(ensembl_res[ensembl_res$regulatory_stable_id == i,])
        })
    reg_vals_df <- Reduce(rbind, reg_vals)
    out <- data.frame( 
        ensembl_reg_id = paste(reg_vals_df$ensembl_reg_id, collapse = "///"),
        ensembl_reg_coordinates =paste(reg_vals_df$ensembl_reg_coordinates, 
                                        collapse = "///"),
        ensembl_reg_type = paste(reg_vals_df$ensembl_reg_type, 
                                collapse = "///"),
        ensembl_reg_tissues = paste(reg_vals_df$ensembl_reg_tissues, 
                                    collapse = "///")
        )
    out
}

#' Merge records for the same ENSEMBL regulatory element
#' 
#' This function collapses the activity status of a 
#' given an ENSEMBL regulatory 
#' element in different tissues. Notice that tissues
#' identified as inactive will not be reported.
#' 
#' @param tab Results from `biomaRt::getBM` for the 
#' same regulatory element
#' @return `data.frame` of one row after collapsing the 
merge_records <- function(tab)
{

    if (!is(tab, "data.frame")) {
        stop("'tab' argument must be a 'data.frame'")
    }
    vec <- tab[1, , drop = FALSE]
    out <- data.frame( ensembl_reg_id = tab$regulatory_stable_id[1],
                        ensembl_reg_coordinates = paste0( vec$chromosome_name, 
                        ":", vec$chromosome_start, "-", vec$chromosome_end),
                        ensembl_reg_type = vec$feature_type_name )
    
    ## Select activity and tissue
    subtab <- tab[, c("activity", "epigenome_name")]
    
    ## Remove tissues without activity
    subtab <- subtab[!is.na(subtab$activity),]
    states <- unique(subtab$activity)
    
    ## Remove inactive from states
    states <- states[states != "INACTIVE"]
    
    state_vec <- lapply(states, function(x) {
                mini <- subtab[subtab$activity == x,]
                paste(x, ":", paste(mini$epigenome_name, collapse = ";"))
            })
    
    out$ensembl_reg_tissues <- paste(unlist(state_vec), collapse = "/")
    out
}