\name{mkinfit}
\alias{mkinfit}
\title{
Fit a kinetic model to data with one or more state variables.
}
\description{
This function uses the Flexible Modelling Environment package
\code{\link{FME}} to create a function calculating the model cost, which is
then minimised, using the specified initial or fixed parameters and starting
values.
}
\usage{
mkinfit(mkinmod, observed,
parms.ini = "auto",
state.ini = c(100, rep(0, length(mkinmod$diffs) - 1)),
fixed_parms = NULL, fixed_initials = names(mkinmod$diffs)[-1],
solution_type = "auto",
method.modFit = "Marq",
control.modFit = list(),
plot = FALSE, quiet = FALSE, err = NULL, weight = "none",
scaleVar = FALSE,
atol = 1e-8, rtol = 1e-10, n.outtimes = 100,
reweight.method = NULL,
reweight.tol = 1e-8, reweight.max.iter = 10,
trace_parms = FALSE, ...)
}
\arguments{
\item{mkinmod}{
A list of class \code{\link{mkinmod}}, containing the kinetic model to be fitted to the data.
}
\item{observed}{
The observed data. It has to be in the long format as described in
\code{\link{modFit}}, i.e. the first column called "name" must contain the name of the
observed variable for each data point. The second column must contain the
times of observation, named "time". The third column must be named "value"
and contain the observed values. Optionally, a further column can contain
weights for each data point. If it is not named "err", its name must be
passed as a further argument named \code{err} which is then passed on to
\code{\link{modFit}}.
}
\item{parms.ini}{
A named vector of initial values for the parameters, including parameters to
be optimised and potentially also fixed parameters as indicated by \code{fixed_parms}.
If set to "auto", initial values for rate constants are set to default values.
Using parameter names that are not in the model gives an error.
It is possible to only specify a subset of the parameters that the model
needs. You can use the parameter lists "bparms.ode" from a previously
fitted model, which contains the differential equation parameters from this
model. This works nicely if the models are nested. An example is given
below.
}
\item{state.ini}{
A named vector of initial values for the state variables of the model. In case the
observed variables are represented by more than one model variable, the names will
differ from the names of the observed variables (see \code{map} component of
\code{\link{mkinmod}}). The default is to set the initial value of the first model
variable to 100 and all others to 0.
}
\item{fixed_parms}{
The names of parameters that should not be optimised but rather kept at the values
specified in \code{parms.ini}.
}
\item{fixed_initials}{
The names of model variables for which the initial state at time 0 should be excluded
from the optimisation. Defaults to all state variables except for the first one.
}
\item{solution_type}{
If set to "eigen", the solution of the system of differential equations is based on the
spectral decomposition of the coefficient matrix in cases that this is
possible. If set to "deSolve", a numerical ode solver from package
\code{\link{deSolve}} is used. If set to "analytical", an analytical solution
of the model is used. This is only implemented for simple degradation experiments
with only one state variable, i.e. with no metabolites. The default is "auto",
which uses "analytical" if possible, otherwise "eigen" if the model can be expressed
using eigenvalues and eigenvectors, and finally "deSolve" for the remaining
models (time dependence of degradation rates and metabolites).
}
\item{method.modFit}{
The optimisation method passed to \code{\link{modFit}}. The default "Marq" is the Levenberg Marquardt
algorithm \code{\link{nls.lm}} from the package \code{minpack.lm}. Often other methods need
more iterations to find the same result. When using "Pseudo", "upper" and "lower" need to be
specified for the transformed parameters.
}
\item{control.modFit}{
Additional arguments passed to the optimisation method used by \code{\link{modFit}}.
}
\item{plot}{
Should the observed values and the numerical solutions be plotted at each stage
of the optimisation?
}
\item{quiet}{
Suppress printing out the current model cost after each improvement?
}
\item{err }{either \code{NULL}, or the name of the column with the
\emph{error} estimates, used to weigh the residuals (see details of
\code{\link{modCost}}); if \code{NULL}, then the residuals are not weighed.
}
\item{weight}{only if \code{err}=\code{NULL}: how to weight the
residuals, one of "none", "std", "mean", see details of \code{\link{modCost}}.
}
\item{scaleVar}{
Will be passed to \code{\link{modCost}}. Default is not to scale Variables according
to the number of observations.
}
\item{atol}{
Absolute error tolerance, passed to \code{\link{ode}}. Default is 1e-8,
lower than in \code{\link{lsoda}}.
}
\item{rtol}{
Absolute error tolerance, passed to \code{\link{ode}}. Default is 1e-10,
much lower than in \code{\link{lsoda}}.
}
\item{n.outtimes}{
The length of the dataseries that is produced by the model prediction
function \code{\link{mkinpredict}}. This impacts the accuracy of
the numerical solver if that is used (see \code{solution} argument.
The default value is 100.
}
\item{reweight.method}{
The method used for iteratively reweighting residuals, also known
as iteratively reweighted least squares (IRLS). Default is NULL,
the other method implemented is called "obs", meaning that each
observed variable is assumed to have its own variance, this is
estimated from the fit and used for weighting the residuals
in each iteration until convergence of this estimate up to
\code{reweight.tol} or up to the maximum number of iterations
specified by \code{reweight.maxiter}.
}
\item{reweight.tol}{
Tolerance for convergence criterion for the variance components
in IRLS fits.
}
\item{reweight.max.iter}{
Maximum iterations in IRLS fits.
}
\item{trace_parms}{
Should a trace of the parameter values be listed?
}
\item{\dots}{
Further arguments that will be passed to \code{\link{modFit}}.
}
}
\value{
A list with "mkinfit" and "modFit" in the class attribute.
A summary can be obtained by \code{\link{summary.mkinfit}}.
}
\note{
The implementation of iteratively reweighted least squares is inspired by the
work of the KinGUII team at Bayer Crop Science (Walter Schmitt and Zhenglei
Gao). A similar implemention can also be found in CAKE 2.0, which is the
other GUI derivative of mkin, sponsored by Syngenta.
}
\author{
Johannes Ranke <jranke@uni-bremen.de>
}
\examples{
# One parent compound, one metabolite, both single first order.
SFO_SFO <- mkinmod(
parent = list(type = "SFO", to = "m1", sink = TRUE),
m1 = list(type = "SFO"))
# Fit the model to the FOCUS example dataset D using defaults
fit <- mkinfit(SFO_SFO, FOCUS_2006_D)
summary(fit)
# Use stepwise fitting, using optimised parameters from parent only fit, FOMC
\dontrun{
FOMC <- mkinmod(parent = list(type = "FOMC"))
FOMC_SFO <- mkinmod(
parent = list(type = "FOMC", to = "m1", sink = TRUE),
m1 = list(type = "SFO"))
# Fit the model to the FOCUS example dataset D using defaults
fit.FOMC_SFO <- mkinfit(FOMC_SFO, FOCUS_2006_D)
# Use starting parameters from parent only FOMC fit
fit.FOMC = mkinfit(FOMC, FOCUS_2006_D, plot=TRUE)
fit.FOMC_SFO <- mkinfit(FOMC_SFO, FOCUS_2006_D,
parms.ini = fit.FOMC$bparms.ode, plot=TRUE)
}
# Use stepwise fitting, using optimised parameters from parent only fit, SFORB
SFORB <- mkinmod(parent = list(type = "SFORB"))
SFORB_SFO <- mkinmod(
parent = list(type = "SFORB", to = "m1", sink = TRUE),
m1 = list(type = "SFO"))
# Fit the model to the FOCUS example dataset D using defaults
fit.SFORB_SFO <- mkinfit(SFORB_SFO, FOCUS_2006_D)
# Use starting parameters from parent only SFORB fit (not really needed in this case)
fit.SFORB = mkinfit(SFORB, FOCUS_2006_D)
fit.SFORB_SFO <- mkinfit(SFORB_SFO, FOCUS_2006_D, parms.ini = fit.SFORB$bparms.ode, plot=TRUE)
# Weighted fits, including IRLS
SFO_SFO.ff <- mkinmod(parent = list(type = "SFO", to = "m1"),
m1 = list(type = "SFO"), use_of_ff = "max")
f.noweight <- mkinfit(SFO_SFO.ff, FOCUS_2006_D)
summary(f.noweight)
f.irls <- mkinfit(SFO_SFO.ff, FOCUS_2006_D, reweight.method = "obs")
summary(f.irls)
f.w.mean <- mkinfit(SFO_SFO.ff, FOCUS_2006_D, weight = "mean")
summary(f.w.mean)
f.w.mean.irls <- mkinfit(SFO_SFO.ff, FOCUS_2006_D, weight = "mean",
reweight.method = "obs")
summary(f.w.mean.irls)
# Manual weighting
dw <- FOCUS_2006_D
errors <- c(parent = 2, m1 = 1)
dw$err.man <- errors[FOCUS_2006_D$name]
f.w.man <- mkinfit(SFO_SFO.ff, dw, err = "err.man")
summary(f.w.man)
f.w.man.irls <- mkinfit(SFO_SFO.ff, dw, err = "err.man",
reweight.method = "obs")
summary(f.w.man.irls)
}
\keyword{ models }
\keyword{ optimize }
