# Was Id: mkinmod.R 71 2010-09-12 01:13:36Z jranke
# Some of the CAKE R modules are based on mkin
# Portions Johannes Ranke, 2010
# Contact: mkin-devel@lists.berlios.de
# Modifications developed by Hybrid Intelligence (formerly Tessella), part of
# Capgemini Engineering, for Syngenta, Copyright (C) 2011-2022 Syngenta
# Tessella Project Reference: 6245, 7247, 8361, 7414, 10091
# The CAKE R modules are free software: you can redistribute it and/or modify
# it under the terms of the GNU General Public License as published by
# the Free Software Foundation, either version 3 of the License, or
# (at your option) any later version.
#
# This program is distributed in the hope that it will be useful,
# but WITHOUT ANY WARRANTY; without even the implied warranty of
# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
# GNU General Public License for more details.
#
# You should have received a copy of the GNU General Public License
# along with this program. If not, see <http://www.gnu.org/licenses/>.
CakeModel <- function(..., use_of_ff = "max")
{
# While spec is modified throughout this function, topology is added as-is to the returned model
topology <- list(...)
spec <- list(...)
obs_vars <- names(spec)
if (!use_of_ff %in% c("min", "max")) stop("The use of formation fractions 'use_of_ff' can only be 'min' or 'max'")
# differential equations, parameter names and a mapping from model variables
# to observed variables. If possible, a matrix representation of the
# differential equations is included
parms <- vector()
diffs <- vector()
map <- list()
nlt <- list()
# Establish list of differential equations
for (varname in obs_vars)
{
if(is.null(spec[[varname]]$type)) stop("Every argument to CakeModel must be a list containing a type component")
if(!spec[[varname]]$type %in% c("SFO", "FOMC", "DFOP", "HS", "IORE")) stop("Available types are SFO, FOMC, DFOP, HS and IORE only")
new_parms <- vector()
# New (sub)compartments (boxes) needed for the model type
if (spec[[varname]]$type == "DFOP" && varname != "Parent"){
# If this is a DFOP metabolite, we need to form a system of two differential equations
# (see FOCUS page 137)
new_boxes <- paste(varname, c("1", "2"), sep="_")
} else{
new_boxes <- varname
}
map[[varname]] <- new_boxes
names(map[[varname]]) <- rep(spec[[varname]]$type, length(new_boxes))
# Start a new differential equation for each new box
new_diffs <- paste("d_", new_boxes, " =", sep="")
# Turn on sink if not specified otherwise
if(is.null(spec[[varname]]$sink)) spec[[varname]]$sink <- TRUE
# Construct and add SFO term and add SFO parameters if needed
if(spec[[varname]]$type == "SFO") {
if (use_of_ff == "min") { # Minimum use of formation fractions
if(spec[[varname]]$sink) {
# From p. 53 of the FOCUS kinetics report
k_term <- paste("k", new_boxes[[1]], "sink", sep="_")
nonlinear_term <- paste(k_term, new_boxes[[1]], sep=" * ")
spec[[varname]]$nlt<-nonlinear_term
new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
new_parms <- k_term
ff <- vector()
decline_term <- paste(nonlinear_term, "*", new_boxes[[1]])
} else { # otherwise no decline term needed here
decline_term <- "0"
}
} else {
k_term <- paste("k", new_boxes[[1]], sep="_")
nonlinear_term <- paste(k_term, new_boxes[[1]], sep=" * ")
spec[[varname]]$nlt<-nonlinear_term
new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
new_parms <- k_term
ff <- vector()
decline_term <- paste(nonlinear_term, "*", new_boxes[[1]])
}
}
# Construct and add FOMC term and add FOMC parameters if needed
if(spec[[varname]]$type == "FOMC") {
if(match(varname, obs_vars) != 1) {
stop("Type FOMC is only possible for the first compartment, which is assumed to be the source compartment")
}
# From p. 53 of the FOCUS kinetics report
nonlinear_term <- paste("(alpha/beta) * ((time/beta) + 1)^-1 *", new_boxes[[1]])
spec[[varname]]$nlt<-nonlinear_term
new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
new_parms <- c("alpha", "beta")
ff <- vector()
}
# Construct and add DFOP term and add DFOP parameters if needed
if(spec[[varname]]$type == "DFOP") {
k1_term <- paste("k1", varname, sep="_")
k2_term <- paste("k2", varname, sep="_")
g_term <- paste("g", varname, sep="_")
new_parms <- c(k1_term, k2_term, g_term)
ff <- vector()
if (varname == "Parent"){
# From p. 57 of the FOCUS kinetics report
# Looks like this: paste("((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time))) *", new_boxes[[1]])
nonlinear_term <- paste("((", k1_term, " * ", g_term, " * exp(-", k1_term, " * time) + ", k2_term, " * (1 - ", g_term, ") * exp(-", k2_term, " * time)) / (", g_term, " * exp(-", k1_term, " * time) + (1 - ", g_term, ") * exp(-", k2_term, " * time))) *", new_boxes[[1]])
spec[[varname]]$nlt<-nonlinear_term
new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
} else {
# From p. 137 of the FOCUS kinetics report - two sub-compartments with g applied to initial conditions (in ODE pre-processing) and in formation terms.
first_nonlinear_term <- paste(k1_term, new_boxes[[1]], sep=" * ")
second_nonlinear_term <- paste(k2_term, new_boxes[[2]], sep=" * ")
# CU-150: formation has already been accounted for on the formation into the two sub-compartments; it does not need to be factored in again on the way out
overall_term_for_formation <- paste("(", first_nonlinear_term, " + ", second_nonlinear_term, ")")
spec[[varname]]$nlt <- overall_term_for_formation
new_diffs[[1]] <- paste(new_diffs[[1]], "-", first_nonlinear_term)
new_diffs[[2]] <- paste(new_diffs[[2]], "-", second_nonlinear_term)
}
}
# Construct and add HS term and add HS parameters if needed
if(spec[[varname]]$type == "HS") {
if(match(varname, obs_vars) != 1) {
stop("Type HS is only possible for the first compartment, which is assumed to be the source compartment")
}
# From p. 55 of the FOCUS kinetics report: nonlinear_term <- paste("ifelse(time <= tb, k1, k2)", "*", new_boxes[[1]])
# Replaced this with the smoothed version on the next line to ease convergence.
nonlinear_term <- paste("((k1 - k2) / ( 1 + exp( 300*(time - tb)/(tb + 0.00001) ) ) + k2)", "*", new_boxes[[1]])
spec[[varname]]$nlt<-nonlinear_term
new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
new_parms <- c("k1", "k2", "tb")
ff <- vector()
}
# Construct and add IORE term and add IORE parameters if needed
if(spec[[varname]]$type == "IORE") {
k_term <- paste("k", new_boxes[[1]], sep="_")
nonlinear_term <- paste(k_term, new_boxes[[1]], sep=" * ")
nonlinear_term <- paste(nonlinear_term, "^N")
spec[[varname]]$nlt<-nonlinear_term
new_diffs[[1]] <- paste(new_diffs[[1]], "-", nonlinear_term)
new_parms <- c(k_term, "N")
ff <- vector()
}
# Add observed variable to model
parms <- c(parms, new_parms)
names(new_diffs) <- new_boxes
diffs <- c(diffs, new_diffs)
}
# Transfer between compartments
for (varname in obs_vars) {
to <- spec[[varname]]$to
if(!is.null(to)) {
fraction_left <- NULL
for (target in to) {
target_boxes <- switch(spec[[target]]$type,
SFO = target,
DFOP = paste(target, c("1", "2"), sep="_"))
if(spec[[varname]]$type %in% c("FOMC", "DFOP", "HS", "SFO", "IORE")) {
if ( length(to)==1 && !spec[[varname]]$sink ) {
# There is only one output, so no need for any flow fractions. Just add the whole flow from the parent
formation_term <- spec[[varname]]$nlt
} else {
fraction_to_target <- paste("f", varname, "to", target, sep="_")
fraction_not_to_target <- paste("(1 - ", fraction_to_target, ")", sep="")
if(is.null(fraction_left)) {
fraction_really_to_target <- fraction_to_target
fraction_left <- fraction_not_to_target
} else {
# If this is the last output and there is no sink, it gets what's left
if ( target==tail(to,1) && !spec[[varname]]$sink ) {
fraction_really_to_target <- fraction_left
} else {
fraction_really_to_target <- fraction_to_target
fraction_left <- paste(fraction_left, " - ", fraction_to_target, sep="")
}
}
ff[target] <- fraction_really_to_target
formation_term <- paste(ff[target], "*", spec[[varname]]$nlt)
# Add the flow fraction parameter (if it exists)
if ( target!=tail(to,1) || spec[[varname]]$sink ) {
parms <- c(parms, fraction_to_target)
}
}
if (spec[[target]]$type == "DFOP") {
g_term <- paste("g", target, sep="_")
first_formation_term <- paste(g_term, "*", formation_term)
second_formation_term <- paste("(1 -", g_term, ") *", formation_term)
diffs[[target_boxes[[1]]]] <- paste(diffs[[target_boxes[[1]]]], "+", first_formation_term)
diffs[[target_boxes[[2]]]] <- paste(diffs[[target_boxes[[2]]]], "+", second_formation_term)
} else{
diffs[[target_boxes[[1]]]] <- paste(diffs[[target_boxes[[1]]]], "+", formation_term)
}
}
}
}
}
model <- list(diffs = diffs, parms = parms, map = map, use_of_ff = use_of_ff, topology = topology)
if (exists("ff")) {
model$ff <- ff
}
class(model) <- "mkinmod"
invisible(model)
}
