ToxicoGx: Analysis of Large-Scale Toxico-Genomic Data

#' Computes the AUC for a Drug Dose Viability Curve
#'
#' Returns the AUC (Area Under the drug response Curve) given concentration and viability as input, normalized by the concentration
#' range of the experiment. The area returned is the response (1-Viablility) area, i.e. area under the curve when the response curve
#' is plotted on a log10 concentration scale, with high AUC implying high sensitivity to the drug. The function can calculate both
#' the area under a fitted Hill Curve to the data, and a trapz numeric integral of the actual data provided. Alternatively, the parameters
#' of a Hill Slope returned by logLogisticRegression can be passed in if they already known.
#'
#' @examples
#' dose <- c("0.0025","0.008","0.025","0.08","0.25","0.8","2.53","8")
#' viability <- c("108.67","111","102.16","100.27","90","87","74","57")
#' computeAUC(dose, viability)
#'
#'
#' @param concentration `vector` is a vector of drug concentrations.
#' @param viability `vector` is a vector whose entries are the viability values observed in the presence of the
#' drug concentrations whose logarithms are in the corresponding entries of conc, where viability 0
#' indicates that all cells died, and viability 1 indicates that the drug had no effect on the cells.
#' @param Hill_fit `list or vector` In the order: c("Hill Slope", "E_inf", "EC50"), the parameters of a Hill Slope
#' as returned by logLogisticRegression. If conc_as_log is set then the function assumes logEC50 is passed in, and if
#' viability_as_pct flag is set, it assumes E_inf is passed in as a percent. Otherwise, E_inf is assumed to be a decimal,
#' and EC50 as a concentration.
#' @param conc_as_log `logical`, if true, assumes that log10-concentration data has been given rather than concentration data.
#' @param viability_as_pct `logical`, if false, assumes that viability is given as a decimal rather
#' than a percentage, and returns AUC as a decimal. Otherwise, viability is interpreted as percent, and AUC is returned 0-100.
#' @param trunc `logical`, if true, causes viability data to be truncated to lie between 0 and 1 before
#' curve-fitting is performed.
#' @param area.type Should the area be computed using the actual data ("Actual"), or a fitted curve ("Fitted")
#' @param verbose `logical`, if true, causes warnings thrown by the function to be printed.
#' @return Numeric AUC value
#' @export
#' @importFrom caTools trapz
computeAUC <- function (concentration,
                        viability,
                        Hill_fit,
                        conc_as_log = FALSE,
                        viability_as_pct = TRUE,
                        trunc = TRUE,
                        area.type = c("Fitted", "Actual"),
                        verbose = TRUE
) {

    if (missing(concentration)){
        stop("The concentration values to integrate over must always be provided.")
    }
    if (missing(area.type)) {
        area.type <- "Fitted"
    } else {
        area.type <- match.arg(area.type)
    }
    if (area.type == "Fitted" && missing(Hill_fit)) {
        Hill_fit <- logLogisticRegression(concentration,
                                          viability,
                                          conc_as_log = conc_as_log,
                                          viability_as_pct = viability_as_pct,
                                          trunc = trunc,
                                          verbose = verbose)
        cleanData <- sanitizeInput(conc=concentration,
                                   Hill_fit=Hill_fit,
                                   conc_as_log = conc_as_log,
                                   viability_as_pct = viability_as_pct,
                                   trunc = trunc,
                                  verbose = verbose)
        pars <- cleanData[["Hill_fit"]]
        concentration <- cleanData[["log_conc"]]
    } else if (area.type == "Fitted" && !missing(Hill_fit)){
        cleanData <- sanitizeInput(conc = concentration,
                                   viability = viability,
                                   Hill_fit = Hill_fit,
                                   conc_as_log = conc_as_log,
                                   viability_as_pct = viability_as_pct,
                                   trunc = trunc,
                                   verbose = verbose)
        pars <- cleanData[["Hill_fit"]]
        concentration <- cleanData[["log_conc"]]
     } else if (area.type == "Actual" && !missing(viability)){
        cleanData <- sanitizeInput(conc = concentration,
                                   viability = viability,
                                   conc_as_log = conc_as_log,
                                   viability_as_pct = viability_as_pct,
                                   trunc = trunc,
                                   verbose = verbose)
        concentration <- cleanData[["log_conc"]]
        viability <- cleanData[["viability"]]
    } else if (area.type == "Actual" && missing(viability)){
        stop("To calculate the actual area using a trapezoid integral, the raw
             viability values are needed!")
    }
    if (length(concentration) < 2) {
        return(NA)
    }
    a <- min(concentration)
    b <- max(concentration)
    if (area.type == "Actual") {
        trapezoid.integral <- caTools::trapz(concentration, viability)
        AUC <- 1 - trapezoid.integral / (b - a)
    }
    else {
        if(pars[2]==1){
            AUC <- 0
      }else if(pars[1]==0){
          AUC <- (1-pars[2])/2
      } else {
          AUC <- as.numeric((1 - pars[2]) / (pars[1] * (b - a)) *
                              log10((1 + (10 ^ (b - pars[3])) ^ pars[1]) /
                                      (1 + (10 ^ (a - pars[3])) ^ pars[1])))
      }
    }
    if(viability_as_pct){
      AUC <- AUC*100
    }
    return(AUC)
}