mkinfit. mkin 0.9.44.9000

Usage

mkinfit(mkinmod, observed,  parms.ini = "auto", state.ini = "auto", fixed_parms = NULL, fixed_initials = names(mkinmod$diffs)[-1],  from_max_mean = FALSE, solution_type = c("auto", "analytical", "eigen", "deSolve"), method.ode = "lsoda", use_compiled = "auto", method.modFit = c("Port", "Marq", "SANN", "Nelder-Mead", "BFGS", "CG", "L-BFGS-B"), maxit.modFit = "auto", control.modFit = list(), transform_rates = TRUE, transform_fractions = TRUE, 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

mkinmod: - A list of class mkinmod, containing the kinetic model to be - fitted to the data, or one of the shorthand names ("SFO", "FOMC", "DFOP", - "HS", "SFORB"). If a shorthand name is given, a parent only degradation - model is generated for the variable with the highest value in - observed. -
observed: - The observed data. It has to be in the long format as described in - 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. Its name must be passed as a - further argument named err which is then passed on to - modFit. -
parms.ini: - A named vector of initial values for the parameters, including parameters - to be optimised and potentially also fixed parameters as indicated by - 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. -
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 map component of mkinmod). The default is to set - the initial value of the first model variable to the mean of the time zero - values for the variable with the maximum observed value, and all others to 0. - If this variable has no time zero observations, its initial value is set to 100. -
fixed_parms: - The names of parameters that should not be optimised but rather kept at the - values specified in parms.ini. -
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. -
from_max_mean: - If this is set to TRUE, and the model has only one observed variable, then - data before the time of the maximum observed value (after averaging for each - sampling time) are discarded, and this time is subtracted from all - remaining time values, so the time of the maximum observed mean value is - the new time zero. -
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 - 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). This argument is passed - on to the helper function mkinpredict. -
method.ode: - The solution method passed via mkinpredict to - ode in case the solution type is "deSolve". The default - "lsoda" is performant, but sometimes fails to converge. -
use_compiled: - If set to FALSE, no compiled version of the mkinmod - model is used, in the calls to mkinpredict even if - a compiled verion is present. -
method.modFit: - The optimisation method passed to modFit. - - In order to optimally deal with problems where local minima occur, the - "Port" algorithm is now used per default as it is less prone to get trapped - in local minima and depends less on starting values for parameters than - the Levenberg Marquardt variant selected by "Marq". However, "Port" needs - more iterations. - - The former default "Marq" is the Levenberg Marquardt algorithm - nls.lm from the package minpack.lm and usually needs - the least number of iterations. - - The "Pseudo" algorithm is not included because it needs finite parameter bounds - which are currently not supported. - - The "Newton" algorithm is not included because its number of iterations - can not be controlled by control.modFit and it does not appear - to provide advantages over the other algorithms. -
maxit.modFit: - Maximum number of iterations in the optimisation. If not "auto", this will - be passed to the method called by modFit, overriding - what may be specified in the next argument control.modFit. -
control.modFit: - Additional arguments passed to the optimisation method used by - modFit. -
transform_rates: - Boolean specifying if kinetic rate constants should be transformed in the - model specification used in the fitting for better compliance with the - assumption of normal distribution of the estimator. If TRUE, also - alpha and beta parameters of the FOMC model are log-transformed, as well - as k1 and k2 rate constants for the DFOP and HS models and the break point - tb of the HS model. - If FALSE, zero is used as a lower bound for the rates in the optimisation. -
transform_fractions: - Boolean specifying if formation fractions constants should be transformed in the - model specification used in the fitting for better compliance with the - assumption of normal distribution of the estimator. The default (TRUE) is - to do transformations. If TRUE, the g parameter of the DFOP and HS - models are also transformed, as they can also be seen as compositional - data. The transformation used for these transformations is the - ilr transformation. -
plot: - Should the observed values and the numerical solutions be plotted at each - stage of the optimisation? -
quiet: - Suppress printing out the current model cost after each improvement? -
err: either NULL, or the name of the column with the - error estimates, used to weigh the residuals (see details of - modCost); if NULL, then the residuals are not weighed. -
weight: - only if err=NULL: how to weight the residuals, one of "none", - "std", "mean", see details of modCost. -
scaleVar: - Will be passed to modCost. Default is not to scale Variables - according to the number of observations. -
atol: - Absolute error tolerance, passed to ode. Default is 1e-8, - lower than in lsoda. -
rtol: - Absolute error tolerance, passed to ode. Default is 1e-10, - much lower than in lsoda. -
n.outtimes: - The length of the dataseries that is produced by the model prediction - function mkinpredict. This impacts the accuracy of - the numerical solver if that is used (see solution_type argument. - The default value is 100. -
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 - reweight.tol or up to the maximum number of iterations - specified by reweight.max.iter. -
reweight.tol: - Tolerance for convergence criterion for the variance components - in IRLS fits. -
reweight.max.iter: - Maximum iterations in IRLS fits. -
trace_parms: - Should a trace of the parameter values be listed? -
...: - Further arguments that will be passed to modFit. -

- -

Description

- -

This function uses the Flexible Modelling Environment package - FME to create a function calculating the model cost, i.e. the - deviation between the kinetic model and the observed data. This model cost is - then minimised using the Port algorithm nlminb, - using the specified initial or fixed parameters and starting values. - Per default, parameters in the kinetic models are internally transformed in order - to better satisfy the assumption of a normal distribution of their estimators. - In each step of the optimsation, the kinetic model is solved using the - function mkinpredict. The variance of the residuals for each - observed variable can optionally be iteratively reweighted until convergence - using the argument reweight.method = "obs".

- -

Value

- -

- A list with "mkinfit" and "modFit" in the class attribute. - A summary can be obtained by 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.

- -

Note

- -

When using the "IORE" submodel for metabolites, fitting with - "transform_rates = TRUE" (the default) often leads to failures of the - numerical ODE solver. In this situation it may help to switch off the - internal rate transformation.

- -

Examples

# Use shorthand notation for parent only degradation
-fit <- mkinfit("FOMC", FOCUS_2006_C, quiet = TRUE)
-summary(fit)
-
-mkin version:    0.9.44.9000 
-R version:       3.3.1 
-Date of fit:     Sat Sep 10 05:19:38 2016 
-Date of summary: Sat Sep 10 05:19:38 2016 
-
-Equations:
-d_parent = - (alpha/beta) * 1/((time/beta) + 1) * parent
-
-Model predictions using solution type analytical 
-
-Fitted with method Port using 64 model solutions performed in 0.148 s
-
-Weighting: none
-
-Starting values for parameters to be optimised:
-         value   type
-parent_0  85.1  state
-alpha      1.0 deparm
-beta      10.0 deparm
-
-Starting values for the transformed parameters actually optimised:
-              value lower upper
-parent_0  85.100000  -Inf   Inf
-log_alpha  0.000000  -Inf   Inf
-log_beta   2.302585  -Inf   Inf
-
-Fixed parameter values:
-None
-
-Optimised, transformed parameters with symmetric confidence intervals:
-          Estimate Std. Error    Lower   Upper
-parent_0  85.87000     2.2460 80.38000 91.3700
-log_alpha  0.05192     0.1605 -0.34080  0.4446
-log_beta   0.65100     0.2801 -0.03452  1.3360
-
-Parameter correlation:
-          parent_0 log_alpha log_beta
-parent_0    1.0000   -0.2033  -0.3624
-log_alpha  -0.2033    1.0000   0.9547
-log_beta   -0.3624    0.9547   1.0000
-
-Residual standard error: 2.275 on 6 degrees of freedom
-
-Backtransformed parameters:
-Confidence intervals for internally transformed parameters are asymmetric.
-t-test (unrealistically) based on the assumption of normal distribution
-for estimators of untransformed parameters.
-         Estimate t value    Pr(>t)   Lower  Upper
-parent_0   85.870  38.230 1.069e-08 80.3800 91.370
-alpha       1.053   6.231 3.953e-04  0.7112  1.560
-beta        1.917   3.570 5.895e-03  0.9661  3.806
-
-Chi2 error levels in percent:
-         err.min n.optim df
-All data   6.657       3  6
-parent     6.657       3  6
-
-Estimated disappearance times:
-        DT50  DT90 DT50back
-parent 1.785 15.15     4.56
-
-Data:
- time variable observed predicted residual
-    0   parent     85.1    85.875  -0.7749
-    1   parent     57.9    55.191   2.7091
-    3   parent     29.9    31.845  -1.9452
-    7   parent     14.6    17.012  -2.4124
-   14   parent      9.7     9.241   0.4590
-   28   parent      6.6     4.754   1.8460
-   63   parent      4.0     2.102   1.8977
-   91   parent      3.9     1.441   2.4590
-  119   parent      0.6     1.092  -0.4919
-
-
-# One parent compound, one metabolite, both single first order.
-# Use mkinsub for convenience in model formulation. Pathway to sink included per default.
-SFO_SFO <- mkinmod(
-  parent = mkinsub("SFO", "m1"),
-  m1 = mkinsub("SFO"))
-
-Successfully compiled differential equation model from auto-generated C code.
-# Fit the model to the FOCUS example dataset D using defaults
-print(system.time(fit <- mkinfit(SFO_SFO, FOCUS_2006_D, 
-                           solution_type = "eigen", quiet = TRUE)))
-
-   user  system elapsed 
-  1.236   1.188   0.911 
-
-coef(fit)
-
-         parent_0 log_k_parent_sink   log_k_parent_m1     log_k_m1_sink 
-         99.59848          -3.03822          -2.98030          -5.24750 
-
-endpoints(fit)
-
-$ff
-parent_sink   parent_m1     m1_sink 
-   0.485524    0.514476    1.000000 
-
-$SFORB
-logical(0)
-
-$distimes
-             DT50      DT90
-parent   7.022929  23.32967
-m1     131.760712 437.69961
-
-
-## Not run: 
-# # deSolve is slower when no C compiler (gcc) was available during model generation
-# print(system.time(fit.deSolve <- mkinfit(SFO_SFO, FOCUS_2006_D, 
-#                            solution_type = "deSolve")))
-# coef(fit.deSolve)
-# endpoints(fit.deSolve)
-# ## End(Not run)
-
-# Use stepwise fitting, using optimised parameters from parent only fit, FOMC
-## Not run: 
-# FOMC_SFO <- mkinmod(
-#   parent = mkinsub("FOMC", "m1"),
-#   m1 = mkinsub("SFO"))
-# # Fit the model to the FOCUS example dataset D using defaults
-# fit.FOMC_SFO <- mkinfit(FOMC_SFO, FOCUS_2006_D)
-# # Use starting parameters from parent only FOMC fit
-# fit.FOMC = mkinfit("FOMC", FOCUS_2006_D, plot=TRUE)
-# fit.FOMC_SFO <- mkinfit(FOMC_SFO, FOCUS_2006_D, 
-#   parms.ini = fit.FOMC$bparms.ode, plot=TRUE)
-# 
-# # Use stepwise fitting, using optimised parameters from parent only fit, SFORB
-# SFORB_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)
-# fit.SFORB_SFO.deSolve <- mkinfit(SFORB_SFO, FOCUS_2006_D, solution_type = "deSolve")
-# # 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$bparms.ode)
-# ## End(Not run)
-
-## Not run: 
-# # Weighted fits, including IRLS
-# SFO_SFO.ff <- mkinmod(parent = mkinsub("SFO", "m1"),
-#                       m1 = mkinsub("SFO"), use_of_ff = "max")
-# f.noweight <- mkinfit(SFO_SFO.ff, FOCUS_2006_D)
-# summary(f.noweight)
-# f.irls <- mkinfit(SFO_SFO.ff, FOCUS_2006_D, reweight.method = "obs")
-# summary(f.irls)
-# f.w.mean <- mkinfit(SFO_SFO.ff, FOCUS_2006_D, weight = "mean")
-# summary(f.w.mean)
-# f.w.value <- mkinfit(SFO_SFO.ff, subset(FOCUS_2006_D, value != 0), err = "value")
-# summary(f.w.value)
-# ## End(Not run)
-
-## Not run: 
-# # Manual weighting
-# dw <- FOCUS_2006_D
-# errors <- c(parent = 2, m1 = 1)
-# dw$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)
-# ## End(Not run)
-

- - -

Author

- - Johannes Ranke - - -

- Fit a kinetic model to data with one or more state variables -

Usage

Arguments

Description

Value

Note

Note

Examples

See also

Author