R/bmdcalc.R

In DRomics: Dose Response for Omics

# internally used function
calcBMD <- function(y0, delta, xext, yext, dosemin, dosemax, ydosemax, func,
                    func_xinlog, b, c, d, e, g, minBMD, ratio2switchinlog) {
  
  if ((dosemax / dosemin) > ratio2switchinlog) {
    workwithxinlog <- TRUE
    func4uniroot <- func_xinlog
    firstinterval <- c(log(minBMD), log(xext))
    secondinterval <- c(log(max(xext, minBMD)), log(dosemax))
  } else {
    workwithxinlog <- FALSE
    func4uniroot <- func
    firstinterval <- c(minBMD, xext)
    secondinterval <- c(max(xext, minBMD), dosemax)
  }
  
  finalroot <- NA
  if (g > 0) { # Umbrella shape
    threshold <- y0 + delta # we first seek the BMR above d
    # value of y - threshold at minBMD
    funcatminBMD <-  func(minBMD, b = b, c = c, d = d, e = e, g = g, threshold = threshold)
    if (y0 < threshold && threshold < yext && xext != 0) { # BMR in first phase
      # xext != 0 is for some rare Gaussprobit models with e = 0 so
      # with ext = 0 and thus increasing
      if ((xext <= minBMD) || (funcatminBMD >= 0)) {
        finalroot <- workwithxinlog * log(minBMD) + (1 - workwithxinlog) * minBMD
      } else { # then we seek the BMR above y0
        finalroot <- stats::uniroot(func4uniroot, interval = firstinterval,
                                    b = b, c = c, d = d, e = e, g = g,
                                    threshold = threshold)$root
      }
    } else { # BMR may be in the second phase
      threshold <- y0 - delta
      funcatminBMD <- func(minBMD, b = b, c = c, d = d, e = e, g = g, threshold = threshold)
      if (funcatminBMD <= 0) {
        finalroot <- workwithxinlog * log(minBMD) + (1 - workwithxinlog) * minBMD
      } else {
        if (c < y0 && threshold > ydosemax) {
          # then we seek the BMR below y0 (possible only if c<y0)
          finalroot <- stats::uniroot(func4uniroot, interval = secondinterval,
                                      b = b, c = c, d = d, e = e, g = g,
                                      threshold = threshold)$root
        }
      }
    }
  }
  
  if (g < 0) { # U shape
    threshold <- y0 - delta # we first seek the BMR below y0
    funcatminBMD <- func(minBMD, b = b, c = c, d = d, e = e, g = g, threshold = threshold)
    if (y0 > threshold && threshold > yext && xext != 0) { # BMR in first phase
      # xext != 0 is for some rare Gaussprobit models with e = 0 so
      # with ext = 0 and thus decreasing
      if ((xext <= minBMD) || (funcatminBMD <= 0)) {
        finalroot <- workwithxinlog * log(minBMD) + (1 - workwithxinlog) * minBMD
      } else {
        finalroot <- stats::uniroot(func4uniroot, interval = firstinterval,
                                    b = b, c = c, d = d, e = e, g = g,
                                    threshold = threshold)$root
      }
    } else { # BMR may be in the second phase
      threshold <- y0 + delta
      funcatminBMD <- func(minBMD, b = b, c = c, d = d, e = e, g = g, threshold = threshold)
      if (funcatminBMD >= 0) {
        finalroot <- workwithxinlog * log(minBMD) + (1 - workwithxinlog) * minBMD
      } else {
        if (c > y0 && threshold < ydosemax) {  # then we seek the BMR above y0 (possible only if c > y0)
          finalroot <- stats::uniroot(func4uniroot, interval = secondinterval,
                                      b = b, c = c, d = d, e = e, g = g,
                                      threshold = threshold)$root
        }
      }
    }
  }
  
  if (workwithxinlog) {
    return(list(threshold = threshold, BMD = exp(finalroot)))
  } else {
    return(list(threshold = threshold, BMD = finalroot))
  }
}

### Calculation of BMD values (x-fold or z-SD) from fitted dose-response curves
bmdcalc <- function(f, z = 1, x = 10, minBMD, ratio2switchinlog = 100) {
  
  # Checks
  if (!inherits(f, "drcfit"))
    stop("Use only with 'drcfit' objects, created with the function drcfit.")
  
  dfitall <- f$fitres
  nselect <- length(dfitall$irow)
  dosemax <- max(f$omicdata$dose)
  dosemin <- min(f$omicdata$dose[f$omicdata$dose != 0])
  
  if (missing(minBMD)) {
    minBMD <- dosemin / 100
  }  else { # could be changed
    if (minBMD > dosemin) {
      warning("You can fix minBMD only to a value smaller than the minimal non null tested dose.")
      minBMD <- dosemin / 100
    }
  }
  
  if (minBMD <= 0) {
    stop("minBMD should be a stricly positive value.")
  }
  
  dcalc <- data.frame(xextrem = dfitall$xextrem,
                      yextrem = rep(NA, nselect),
                      y0 = dfitall$y0,
                      ydosemax = rep(NA, nselect),
                      yp = rep(NA, nselect),
                      ysd = rep(NA, nselect),
                      BMDp = rep(NA, nselect),
                      BMDsd = rep(NA, nselect)
  )
  
  xdiv100 <- x / 100 # x in relative value and not in percentage
  
  for (i in 1:nselect) {
    b <- dfitall$b[i]
    c <- dfitall$c[i]
    d <- dfitall$d[i]
    e <- dfitall$e[i]
    g <- dfitall$f[i] # f is renamed g
    y0 <- dcalc$y0[i]
    xext <- dcalc$xextrem[i]
    
    modeli <- dfitall$model[i]
    if (modeli == "linear") {
      ydosemax <- dcalc$ydosemax[i] <- flin(x = dosemax, b = b, d = d)
      dcalc$yp[i] <- y0 * (1 + xdiv100 * sign(b))
      dcalc$BMDp[i] <- invlin(dcalc$yp[i], b, d)
      dcalc$ysd[i] <- y0 + z * dfitall$SDres[i] * sign(b)
      dcalc$BMDsd[i] <- invlin(dcalc$ysd[i], b, d)
      
    } else if (modeli == "exponential") {
      ydosemax <- dcalc$ydosemax[i] <- fExpo(x = dosemax, b = b, d = d, e = e)
      dcalc$yp[i] <- y0 * (1 + xdiv100 * sign(e * b))
      dcalc$BMDp[i] <- invExpo(dcalc$yp[i], b, d, e)
      dcalc$ysd[i] <- y0 + z * dfitall$SDres[i] * sign(e * b)
      dcalc$BMDsd[i] <- invExpo(dcalc$ysd[i], b, d, e)
      
    } else if (modeli == "Hill") {
      ydosemax <- dcalc$ydosemax[i] <- fHill(x = dosemax, b = b, c = c, d = d, e = e)
      dcalc$yp[i] <- y0 * (1 + xdiv100 * sign(c - d))
      dcalc$BMDp[i] <- invHill(dcalc$yp[i], b, c, d, e)
      dcalc$ysd[i] <- y0 + z * dfitall$SDres[i] * sign(c - d)
      dcalc$BMDsd[i] <- invHill(dcalc$ysd[i], b, c, d, e)
      
    } else if (modeli == "log-Gauss-probit" && g == 0) {
      ydosemax <- dcalc$ydosemax[i] <- fLGauss5p(x = dosemax, b = b, c = c, d = d, e = e, f = 0)
      dcalc$yp[i] <- y0 * (1 + xdiv100 * sign(c - d))
      dcalc$BMDp[i] <- invLprobit(dcalc$yp[i], b, c, d, e)
      dcalc$ysd[i] <- y0 + z * dfitall$SDres[i] * sign(c - d)
      dcalc$BMDsd[i] <- invLprobit(dcalc$ysd[i], b, c, d, e)
      
    } else if (modeli == "Gauss-probit" && g == 0) {
      ydosemax <- dcalc$ydosemax[i] <- fGauss5p(x = dosemax, b = b, c = c, d = d, e = e, f = 0)
      dcalc$yp[i] <- y0 * (1 + xdiv100 * sign(c - d))
      dcalc$BMDp[i] <- invprobit(dcalc$yp[i], b, c, d, e)
      dcalc$ysd[i] <- y0 + z * dfitall$SDres[i] * sign(c - d)
      dcalc$BMDsd[i] <- invprobit(dcalc$ysd[i], b, c, d, e)
      
    } else
      if (modeli == "Gauss-probit" && g != 0) {
        yext <- dcalc$yextrem[i] <- fGauss5p(xext, b = b, c = c, d = d, e = e, f = g) # g is renamed f
        ydosemax <- dcalc$ydosemax[i] <- fGauss5p(x = dosemax, b = b, c = c, d = d, e = e, f = g)
        deltap <- abs(y0) * xdiv100
        deltasd <- z * dfitall$SDres[i]
        
        resBMDp <- calcBMD(y0 = y0, delta = deltap, xext = xext, yext = yext,
                           dosemin = dosemin, dosemax = dosemax, ydosemax = ydosemax,
                           func = fGauss5pBMR, func_xinlog = fGauss5pBMR_xinlog,
                           b = b, c = c, d = d, e = e, g = g, minBMD = minBMD,
                           ratio2switchinlog = ratio2switchinlog)
        dcalc$yp[i] <- resBMDp$threshold
        dcalc$BMDp[i] <- resBMDp$BMD
        
        resBMDsd <- calcBMD(y0 = y0, delta = deltasd, xext = xext, yext = yext,
                            dosemin = dosemin, dosemax = dosemax, ydosemax = ydosemax,
                            func = fGauss5pBMR, func_xinlog = fGauss5pBMR_xinlog,
                            b = b, c = c, d = d, e = e, g = g, minBMD = minBMD,
                            ratio2switchinlog = ratio2switchinlog)
        dcalc$ysd[i] <- resBMDsd$threshold
        dcalc$BMDsd[i] <- resBMDsd$BMD
        
      } else if (modeli == "log-Gauss-probit" && g != 0) {
        yext <- dcalc$yextrem[i] <- fLGauss5p(xext, b = b, c = c, d = d, e = e, f = g) # g is renamed f
        ydosemax <- dcalc$ydosemax[i] <- fLGauss5p(x = dosemax, b = b, c = c, d = d, e = e, f = g)
        deltap <- abs(y0) * xdiv100
        deltasd <- z * dfitall$SDres[i]
        
        resBMDp <- calcBMD(y0 = y0, delta = deltap, xext = xext, yext = yext,
                           dosemin = dosemin, dosemax = dosemax, ydosemax = ydosemax,
                           func = fLGauss5pBMR, func_xinlog = fLGauss5pBMR_xinlog,
                           b = b, c = c, d = d, e = e, g = g, minBMD = minBMD,
                           ratio2switchinlog = ratio2switchinlog)
        dcalc$yp[i] <- resBMDp$threshold
        dcalc$BMDp[i] <- resBMDp$BMD
        
        resBMDsd <- calcBMD(y0 = y0, delta = deltasd, xext = xext, yext = yext,
                            dosemin = dosemin, dosemax = dosemax, ydosemax = ydosemax,
                            func = fLGauss5pBMR,  func_xinlog = fLGauss5pBMR_xinlog,
                            b = b, c = c, d = d, e = e, g = g, minBMD = minBMD,
                            ratio2switchinlog = ratio2switchinlog)
        dcalc$ysd[i] <- resBMDsd$threshold
        dcalc$BMDsd[i] <- resBMDsd$BMD
      }
    dcalc$BMDsd[i] <- max(dcalc$BMDsd[i], minBMD)
    dcalc$BMDp[i] <- max(dcalc$BMDp[i], minBMD)
  }
  dcalc$BMDp[dcalc$BMDp > dosemax] <- NA
  dcalc$BMDsd[dcalc$BMDsd > dosemax] <- NA
  
  reslist <- list(res = as.data.frame(cbind(dfitall,
                                            data.frame(BMD.zSD = dcalc$BMDsd, BMR.zSD = dcalc$ysd,
                                                       BMD.xfold = dcalc$BMDp, BMR.xfold = dcalc$yp))),
                  z = z, x = x, minBMD = minBMD,
                  ratio2switchinlog = ratio2switchinlog, omicdata = f$omicdata)
  
  return(structure(reslist, class = "bmdcalc"))
}


print.bmdcalc <- function(x, ...) {
  
  if (!inherits(x, "bmdcalc"))
    stop("Use only with 'bmdcalc' objects.")
  
  # count of cases where BMD cannot be reached
  # being outside the range of response values defined by the model
  nNaN.BMD.zSD <- sum(is.nan(x$res$BMD.zSD))
  nNaN.BMD.xfold <- sum(is.nan(x$res$BMD.xfold))
  if ((nNaN.BMD.zSD > 0) || (nNaN.BMD.xfold > 0))
    cat(strwrap(paste0(nNaN.BMD.xfold, " BMD-xfold values and ", nNaN.BMD.zSD,
                       " BMD-zSD values are not defined (coded NaN as the BMR stands outside 
                       the range of response values defined by the model).")), fill = TRUE)
  
  # count of cases where BMD is not yet reached at the highest tested dose
  nNA.BMD.zSD <- sum(is.na(x$res$BMD.zSD) & !is.nan(x$res$BMD.zSD))
  nNA.BMD.xfold <- sum(is.na(x$res$BMD.xfold) & !is.nan(x$res$BMD.xfold))
  if ((nNA.BMD.zSD > 0) || (nNA.BMD.xfold > 0))
    cat(strwrap(paste0(nNA.BMD.xfold, " BMD-xfold values and ", nNA.BMD.zSD,
                       " BMD-zSD values could not be calculated (coded NA as the BMR stands within the 
                       range of response values defined by the model but outside the range of tested doses).")), fill = TRUE)
  
  if ((nNA.BMD.zSD == 0) && (nNA.BMD.xfold == 0) && (nNaN.BMD.zSD == 0) && (nNaN.BMD.xfold == 0))
    cat(strwrap("BMD-xfold and BMD-SD values could be calculated on all the curves 
                (the BMR always stands within the range of response values defined by the model 
                and within the range of tested doses)."), fill = TRUE)
}

plot.bmdcalc <- function(x, BMDtype = c("zSD", "xfold"),
                         plottype = c("ecdf", "hist", "density"),
                         by = c("none", "trend", "model", "typology"),
                         hist.bins = 30,
                         BMD_log_transfo = TRUE,
                         ...) {
  
  if (!inherits(x, "bmdcalc"))
    stop("Use only with 'bmdcalc' objects.")
  
  BMDtype <- match.arg(BMDtype, c("zSD", "xfold"))
  plottype <- match.arg(plottype, c("ecdf", "hist", "density"))
  by <- match.arg(by, c("none", "trend", "model", "typology"))
  
  if (BMDtype == "zSD") {
    dwithNANaN <- data.frame(BMD = x$res$BMD.zSD,
                             trend = x$res$trend, model = x$res$model, typology = x$res$typology)
  } else {
    dwithNANaN <- data.frame(BMD = x$res$BMD.xfold,
                             trend = x$res$trend, model = x$res$model, typology = x$res$typology)
  }
  
  # Remove NA and NaN values if needed
  d <- dwithNANaN[!is.na(dwithNANaN$BMD) & !is.nan(dwithNANaN$BMD), ]
  nremoved <- nrow(dwithNANaN) - nrow(d)
  if (nremoved > 0) {
    warning(strwrap(prefix = "\n", initial = "\n", paste0(nremoved,
                                                          " BMD coded NA or NaN were removed before plotting.")))
  }
  
  if (plottype == "hist") {
    g <- ggplot(data = d, mapping = aes(x = .data$BMD)) +
      geom_histogram(bins = hist.bins)
  } else if (plottype == "density") {
    g <- ggplot(data = d, mapping = aes(x = .data$BMD)) + geom_density(fill = I("grey"))
  } else if (plottype == "ecdf") {
    g <- ggplot(data = d, mapping = aes(x = .data$BMD)) +
      stat_ecdf(geom = "step") + ylab("ECDF")
  }
  
  if (by == "trend")  {
    g <- g + facet_wrap(~ trend)
  } else if (by == "model") {
    g <- g + facet_wrap(~ model)
  } else if (by == "typology") {
    g <- g + facet_wrap(~ typology)
  }
  
  if (BMD_log_transfo) {
    g <- g + scale_x_log10() + xlab("BMD (in log scale)")
  }
  
  return(g)
}