mkin

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The R package mkin provides calculation routines for the analysis of +chemical degradation data, including multicompartment kinetics as +needed for modelling the formation and decline of transformation products, or +if several compartments are involved.

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Installation

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You can install the latest released version from +CRAN from within R:

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install.packages("mkin")
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Background

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In the regulatory evaluation of chemical substances like plant protection +products (pesticides), biocides and other chemicals, degradation data play an +important role. For the evaluation of pesticide degradation experiments, +detailed guidance and helpful tools have been developed as detailed in +'Credits and historical remarks' below.

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Usage

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For a start, have a look a the code examples provided for +plot.mkinfit +and +plot.mmkin, and +at the package vignettes +FOCUS L and +FOCUS D.

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Documentation

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The HTML documentation is +maintained at the R-Forge project site.

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Features

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Highly flexible model specification using +mkinmod, +including equilibrium reactions and using the single first-order +reversible binding (SFORB) model, which will automatically create +two latent state variables for the observed variable.
As of version 0.9-39, fitting of several models to several datasets, optionally in +parallel, is supported, see for example +plot.mmkin.
Model solution (forward modelling) in the function +mkinpredict +is performed either using the analytical solution for the case of +parent only degradation, an eigenvalue based solution if only simple +first-order (SFO) or SFORB kinetics are used in the model, or +using a numeric solver from the deSolve package (default is lsoda).
If a C compiler is installed, the kinetic models are compiled from automatically +generated C code, see
+vignette compiled_models. +The autogeneration of C code was +inspired by the ccSolve package. Thanks +to Karline Soetaert for her work on that.
By default, kinetic rate constants and kinetic formation fractions are +transformed internally using +transform_odeparms +so their estimators can more reasonably be expected to follow +a normal distribution. This has the side effect that no constraints +are needed in the optimisation. Thanks to René Lehmann for the nice +cooperation on this, especially the isometric logration transformation +that is now used for the formation fractions.
A side effect of this is that when parameter estimates are backtransformed +to match the model definition, confidence intervals calculated from +standard errors are also backtransformed to the correct scale, and will +not include meaningless values like negative rate constants or +formation fractions adding up to more than 1, which can not occur in +a single experiment with a single defined radiolabel position.
The usual one-sided t-test for significant difference from zero is nevertheless +shown based on estimators for the untransformed parameters.
Summary and plotting functions. The summary of an mkinfit object is in +fact a full report that should give enough information to be able to +approximately reproduce the fit with other tools.
The chi-squared error level as defined in the FOCUS kinetics guidance +(see below) is calculated for each observed variable.
Iteratively reweighted least squares fitting is implemented in a similar way +as in KinGUII and CAKE (see below). Simply add the argument +reweight = "obs" to your call to mkinfit and a separate variance +componenent for each of the observed variables will be optimised +in a second stage after the primary optimisation algorithm has converged.
When a metabolite decline phase is not described well by SFO kinetics, +SFORB kinetics can be used for the metabolite.

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GUI

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There is a graphical user interface that I consider useful for real work. Please +refer to its documentation page +for installation instructions and a manual.

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News

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Yes, there is a ChangeLog, for the latest CRAN release +and one for the github master branch.

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Credits and historical remarks

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mkin would not be possible without the underlying software stack consisting +of R and the packages deSolve +and FME, to say the least.

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It could not have been written without me being introduced to regulatory fate +modelling of pesticides by Adrian Gurney during my time at Harlan Laboratories +Ltd (formerly RCC Ltd). mkin greatly profits from and largely follows +the work done by the +FOCUS Degradation Kinetics Workgroup, +as detailed in their guidance document from 2006, slightly updated in 2011 and +2014.

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Also, it was inspired by the first version of KinGUI developed by +BayerCropScience, which is based on the MatLab runtime environment.

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The companion package +kinfit (now deprecated) was +started in 2008 and +first published on +CRAN on 01 May 2010.

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The first mkin code was +published on 11 May 2010 and the +first CRAN version +on 18 May 2010.

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In 2011, Bayer Crop Science started to distribute an R based successor to KinGUI named +KinGUII whose R code is based on mkin, but which added, amongst other +refinements, a closed source graphical user interface (GUI), iteratively +reweighted least squares (IRLS) optimisation of the variance for each of the +observed variables, and Markov Chain Monte Carlo (MCMC) simulation +functionality, similar to what is available e.g. in the FME package.

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Somewhat in parallel, Syngenta has sponsored the development of an mkin and +KinGUII based GUI application called CAKE, which also adds IRLS and MCMC, is +more limited in the model formulation, but puts more weight on usability. +CAKE is available for download from the CAKE +website, where you can also +find a zip archive of the R scripts derived from mkin, published under the GPL +license.

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Finally, there is +KineticEval, which contains +a further development of the scripts used for KinGUII, so the different tools +will hopefully be able to learn from each other in the future as well.

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Development

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Contributions are welcome! Your +mkin fork is just a mouse click +away… The master branch on github should always be in good shape, I implement +new features in separate branches now. If you prefer subversion, project +members for the +r-forge project are welcome as well. +Generally, the source code of the latest CRAN version should be available there. +You can also browse the source code at cgit.jrwb.de/mkin.

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