#' Function to calculate endpoints for further use from kinetic models fitted
#' with mkinfit
#'
#' This function calculates DT50 and DT90 values as well as formation fractions
#' from kinetic models fitted with mkinfit. If the SFORB model was specified
#' for one of the parents or metabolites, the Eigenvalues are returned. These
#' are equivalent to the rate constants of the DFOP model, but with the
#' advantage that the SFORB model can also be used for metabolites.
#'
#' Additional DT50 values are calculated from the FOMC DT90 and k1 and k2 from
#' HS and DFOP, as well as from Eigenvalues b1 and b2 of any SFORB models
#'
#' @param fit An object of class [mkinfit] or [nlme.mmkin]
#' or another object that has list components
#' mkinmod containing an [mkinmod] degradation model, and two numeric vectors,
#' bparms.optim and bparms.fixed, that contain parameter values
#' for that model.
#' @importFrom stats optimize
#' @return A list with a matrix of dissipation times named distimes,
#' and, if applicable, a vector of formation fractions named ff
#' and, if the SFORB model was in use, a vector of eigenvalues
#' of these SFORB models, equivalent to DFOP rate constants
#' @note The function is used internally by [summary.mkinfit]
#' and [summary.nlme.mmkin]
#' @author Johannes Ranke
#' @examples
#'
#' fit <- mkinfit("FOMC", FOCUS_2006_C, quiet = TRUE)
#' endpoints(fit)
#' \dontrun{
#' fit_2 <- mkinfit("DFOP", FOCUS_2006_C, quiet = TRUE)
#' endpoints(fit_2)
#' fit_3 <- mkinfit("SFORB", FOCUS_2006_C, quiet = TRUE)
#' endpoints(fit_3)
#' }
#'
#' @export
endpoints <- function(fit) {
ep <- list()
mkinmod <- fit$mkinmod
degparms <- c(fit$bparms.optim, fit$bparms.fixed)
obs_vars <- names(mkinmod$spec)
ep$ff <- vector()
ep$SFORB <- vector()
ep$distimes <- data.frame(
DT50 = rep(NA, length(obs_vars)),
DT90 = rep(NA, length(obs_vars)),
row.names = obs_vars)
for (obs_var in obs_vars) {
type = names(mkinmod$map[[obs_var]])[1]
# Get formation fractions if directly fitted, and calculate remaining fraction to sink
f_names = grep(paste("^f", obs_var, sep = "_"), names(degparms), value=TRUE)
if (length(f_names) > 0) {
f_values = degparms[f_names]
f_to_sink = 1 - sum(f_values)
names(f_to_sink) = ifelse(type == "SFORB",
paste(obs_var, "free", "sink", sep = "_"),
paste(obs_var, "sink", sep = "_"))
for (f_name in f_names) {
ep$ff[[sub("f_", "", sub("_to_", "_", f_name))]] = f_values[[f_name]]
}
ep$ff = append(ep$ff, f_to_sink)
}
# Get the rest
if (type == "SFO") {
k_names = grep(paste("^k", obs_var, sep="_"), names(degparms), value=TRUE)
k_tot = sum(degparms[k_names])
DT50 = log(2)/k_tot
DT90 = log(10)/k_tot
if (mkinmod$use_of_ff == "min" && length(obs_vars) > 1) {
for (k_name in k_names)
{
ep$ff[[sub("k_", "", k_name)]] = degparms[[k_name]] / k_tot
}
}
}
if (type == "FOMC") {
alpha = degparms["alpha"]
beta = degparms["beta"]
DT50 = beta * (2^(1/alpha) - 1)
DT90 = beta * (10^(1/alpha) - 1)
DT50_back = DT90 / (log(10)/log(2)) # Backcalculated DT50 as recommended in FOCUS 2011
ep$distimes[obs_var, c("DT50back")] = DT50_back
}
if (type == "IORE") {
k_names = grep(paste("^k__iore", obs_var, sep="_"), names(degparms), value=TRUE)
k_tot = sum(degparms[k_names])
# From the NAFTA kinetics guidance, p. 5
n = degparms[paste("N", obs_var, sep = "_")]
k = k_tot
# Use the initial concentration of the parent compound
source_name = mkinmod$map[[1]][[1]]
c0 = degparms[paste(source_name, "0", sep = "_")]
alpha = 1 / (n - 1)
beta = (c0^(1 - n))/(k * (n - 1))
DT50 = beta * (2^(1/alpha) - 1)
DT90 = beta * (10^(1/alpha) - 1)
DT50_back = DT90 / (log(10)/log(2)) # Backcalculated DT50 as recommended in FOCUS 2011
ep$distimes[obs_var, c("DT50back")] = DT50_back
if (mkinmod$use_of_ff == "min") {
for (k_name in k_names)
{
ep$ff[[sub("k_", "", k_name)]] = degparms[[k_name]] / k_tot
}
}
}
if (type == "DFOP") {
k1 = degparms["k1"]
k2 = degparms["k2"]
g = degparms["g"]
f <- function(log_t, x) {
t <- exp(log_t)
fraction <- g * exp( - k1 * t) + (1 - g) * exp( - k2 * t)
(fraction - (1 - x/100))^2
}
DT50_k1 = log(2)/k1
DT50_k2 = log(2)/k2
DT90_k1 = log(10)/k1
DT90_k2 = log(10)/k2
DT50 <- try(exp(optimize(f, c(log(DT50_k1), log(DT50_k2)), x=50)$minimum),
silent = TRUE)
DT90 <- try(exp(optimize(f, c(log(DT90_k1), log(DT90_k2)), x=90)$minimum),
silent = TRUE)
if (inherits(DT50, "try-error")) DT50 = NA
if (inherits(DT90, "try-error")) DT90 = NA
DT50_back = DT90 / (log(10)/log(2)) # Backcalculated DT50 as recommended in FOCUS 2011
ep$distimes[obs_var, c("DT50back")] = DT50_back
ep$distimes[obs_var, c("DT50_k1")] = DT50_k1
ep$distimes[obs_var, c("DT50_k2")] = DT50_k2
}
if (type == "HS") {
k1 = degparms["k1"]
k2 = degparms["k2"]
tb = degparms["tb"]
DTx <- function(x) {
DTx.a <- (log(100/(100 - x)))/k1
DTx.b <- tb + (log(100/(100 - x)) - k1 * tb)/k2
if (DTx.a < tb) DTx <- DTx.a
else DTx <- DTx.b
return(DTx)
}
DT50 <- DTx(50)
DT90 <- DTx(90)
DT50_back = DT90 / (log(10)/log(2)) # Backcalculated DT50 as recommended in FOCUS 2011
DT50_k1 = log(2)/k1
DT50_k2 = log(2)/k2
ep$distimes[obs_var, c("DT50back")] = DT50_back
ep$distimes[obs_var, c("DT50_k1")] = DT50_k1
ep$distimes[obs_var, c("DT50_k2")] = DT50_k2
}
if (type == "SFORB") {
# FOCUS kinetics (2006), p. 60 f
k_out_names = grep(paste("^k", obs_var, "free", sep="_"), names(degparms), value=TRUE)
k_out_names = setdiff(k_out_names, paste("k", obs_var, "free", "bound", sep="_"))
k_1output = sum(degparms[k_out_names])
k_12 = degparms[paste("k", obs_var, "free", "bound", sep="_")]
k_21 = degparms[paste("k", obs_var, "bound", "free", sep="_")]
sqrt_exp = sqrt(1/4 * (k_12 + k_21 + k_1output)^2 + k_12 * k_21 - (k_12 + k_1output) * k_21)
b1 = 0.5 * (k_12 + k_21 + k_1output) + sqrt_exp
b2 = 0.5 * (k_12 + k_21 + k_1output) - sqrt_exp
DT50_b1 = log(2)/b1
DT50_b2 = log(2)/b2
DT90_b1 = log(10)/b1
DT90_b2 = log(10)/b2
SFORB_fraction = function(t) {
((k_12 + k_21 - b1)/(b2 - b1)) * exp(-b1 * t) +
((k_12 + k_21 - b2)/(b1 - b2)) * exp(-b2 * t)
}
f_50 <- function(log_t) (SFORB_fraction(exp(log_t)) - 0.5)^2
log_DT50 <- try(optimize(f_50, c(log(DT50_b1), log(DT50_b2)))$minimum,
silent = TRUE)
f_90 <- function(log_t) (SFORB_fraction(exp(log_t)) - 0.1)^2
log_DT90 <- try(optimize(f_90, c(log(DT90_b1), log(DT90_b2)))$minimum,
silent = TRUE)
DT50 = if (inherits(log_DT50, "try-error")) NA
else exp(log_DT50)
DT90 = if (inherits(log_DT90, "try-error")) NA
else exp(log_DT90)
DT50_back = DT90 / (log(10)/log(2)) # Backcalculated DT50 as recommended in FOCUS 2011
for (k_out_name in k_out_names)
{
ep$ff[[sub("k_", "", k_out_name)]] = degparms[[k_out_name]] / k_1output
}
# Return the eigenvalues for comparison with DFOP rate constants
ep$SFORB[[paste(obs_var, "b1", sep="_")]] = b1
ep$SFORB[[paste(obs_var, "b2", sep="_")]] = b2
ep$distimes[obs_var, c("DT50back")] = DT50_back
ep$distimes[obs_var, c(paste("DT50", obs_var, "b1", sep = "_"))] = DT50_b1
ep$distimes[obs_var, c(paste("DT50", obs_var, "b2", sep = "_"))] = DT50_b2
}
if (type == "logistic") {
# FOCUS kinetics (2014) p. 67
kmax = degparms["kmax"]
k0 = degparms["k0"]
r = degparms["r"]
DT50 = (1/r) * log(1 - ((kmax/k0) * (1 - 2^(r/kmax))))
DT90 = (1/r) * log(1 - ((kmax/k0) * (1 - 10^(r/kmax))))
DT50_k0 = log(2)/k0
DT50_kmax = log(2)/kmax
ep$distimes[obs_var, c("DT50_k0")] = DT50_k0
ep$distimes[obs_var, c("DT50_kmax")] = DT50_kmax
}
ep$distimes[obs_var, c("DT50", "DT90")] = c(DT50, DT90)
}
if (length(ep$ff) == 0) ep$ff <- NULL
if (length(ep$SFORB) == 0) ep$SFORB <- NULL
return(ep)
}
