R/epimutations_one_leave_out.R

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

#' @title Epimutations analysis based on outlier detection methods
#' @description This function is similar to 
#' \link[epimutacions]{epimutations} 
#' with the particularity that when 
#' is more than one case sample,  
#' the remaining case samples are included as controls. 
#' @param methy a GenomicRatioSet object
#'  containing the samples for the 
#' analysis. See the constructor function 
#' \link[minfi]{GenomicRatioSet}, 
#' \link[minfi]{makeGenomicRatioSetFromMatrix}. 
#' @param method a character string naming the 
#' outlier detection method to be used. 
#' This can be set as: 
#' \code{"manova"}, \code{"mlm"}, 
#' \code{"iForest"}, \code{"mahdist"}, 
#' \code{"barbosa"} and \code{beta}. 
#' The default is \code{"manova"}. 
#' For more information see \strong{Details}. 
#' @param epi_params the parameters for each method. 
#' See the function \link[epimutacions]{epi_parameters}.
#' @param BPPARAM (\code{"BiocParallelParam"}) 
#' \link[BiocParallel]{BiocParallelParam} object
#' to configure parallelization execution. 
#' By default, execution is non-parallel. 
#' @param verbose logical. If TRUE additional 
#' details about the procedure will provide to the user. 
#' The default is TRUE.
#' @param ... Further parameters passed to `epimutations`
#' @details The function compares a case 
#' sample against a control panel 
#' to identify epimutations in the given 
#' sample. First, the DMRs are identified using the 
#' \link[bumphunter]{bumphunter} approach. 
#' After that, CpGs in those DMRs are 
#' tested in order to detect regions
#' with CpGs being outliers.  
#' For that,  different anomaly 
#' detection methods can be selected:  
#'  * Multivariate Analysis of Variance 
#'  (\code{"manova"}). \link[stats]{manova}
#'  * Multivariate Linear Model (\code{"mlm"})
#'  * Isolation Forest (\code{"iForest"}) 
#'  \link[isotree]{isolation.forest}
#'  * Robust Mahalanobis Distance (\code{"mahdist"}) 
#'  \link[robustbase]{covMcd}
#'  * Barbosa (\code{"barbosa"})
#' @return The function returns an object of class tibble 
#' containing the outliers regions.  
#' The results are composed by the following columns: 
#' * \code{epi_id}: the name of the anomaly detection method that 
#' has been used to detect the epimutation
#' * \code{sample}: the name of the sample where the epimutation was found.
#' * \code{chromosome}, \code{start} and \code{end}: 
#' indicate the location of the epimutation.
#' * \code{sz}: the number of base pairs in the region.
#' * \code{cpg_n}: number of CpGs in the region.
#' * \code{cpg_ids}: differentially methylated CpGs names.
#' * \code{outlier_score}: 
#'    * For method \code{manova} it provides the approximation 
#'    to F-test and the Pillai score, separated by \code{/}.
#'    * For method \code{mlm} it provides the approximation to 
#'    F-test and the R2 of the model, separated by \code{/}.
#'    * For method \code{iForest} it provides the 
#'    magnitude of the outlier score.
#'    * For methods \code{barbosa} and \code{mahdist} is filled with NA.
#' * \code{outlier_significance}: 
#'    * For methods \code{manova}, \code{mlm}, and \code{iForest} 
#'    it provides the p-value obtained from the model.
#'    * For method \code{barbosa} and \code{mahdist} is filled with NA.
#' * \code{outlier_direction}: indicates the direction of 
#' the outlier with \code{"hypomethylation"} and \code{"hypermethylation"}
#'    * For \code{manova}, \code{mlm}, \code{iForest}, and \code{mahdist} 
#'    it is computed from the values obtained from bumphunter.
#'    * For \code{barbosa} it is computed from the location of 
#'    the sample in the reference distribution (left vs. right outlier).
#' @examples 
#' data(GRset)
#' manova_result <- epimutations_one_leave_out(GRset, 
#'                                             method = "manova")
#' @importFrom BiocParallel bplapply SerialParam 
#' @export 
#' 
#' 
epimutations_one_leave_out <- function(methy, method = "manova", 
                                    epi_params = epi_parameters(), 
                                    BPPARAM = BiocParallel::SerialParam(),
                                    verbose = TRUE, ...)
{
    if (!is(methy, "GenomicRatioSet")) {
        stop(
            "Input data 'methy' must be a 'GenomicRatioSet'.
            'makeGenomicRatioSetFromMatrix' function from 'minfi' package
            can be useful to create a 'GenomicRatioSet' class object"
        )
    }
    
    if (!requireNamespace("methods"))
        stop("'methods' package not avaibale")
    
    rst <- do.call(rbind,
                    BiocParallel::bplapply(colnames(methy), function(case) {
                        case_samples <- methy[, case]
                        control_panel <-  methy[,!colnames(methy) %in% case]
                        epimutations( case_samples, control_panel,
                            method, epi_params = epi_params, verbose = verbose,
                            ... )
                    }, BPPARAM = BPPARAM))

    return(rst)
}