From a9427a09abdf7ce9aaeae7c7190f90c8f2e5ef52 Mon Sep 17 00:00:00 2001 From: Johannes Ranke Date: Mon, 15 Feb 2021 14:08:13 +0100 Subject: Improve README, introductory vignette and some other docs Also bump version to 1.0.3. --- docs/index.html | 45 ++++++++++++++++++++++++++++++++++++--------- 1 file changed, 36 insertions(+), 9 deletions(-) (limited to 'docs/index.html') diff --git a/docs/index.html b/docs/index.html index 51571c81..88f118ea 100644 --- a/docs/index.html +++ b/docs/index.html @@ -37,7 +37,7 @@ mkin - 1.0.2 + 1.0.3 @@ -132,23 +132,40 @@

Features

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+General

  • 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.
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  • 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).
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  • 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.
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  • 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 log-ratio transformation that is now used for the formation fractions.
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  • 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.
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  • When a metabolite decline phase is not described well by SFO kinetics, SFORB kinetics can be used for the metabolite.
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  • Three different error models can be selected using the argument error_model to the mkinfit function.
  • The ‘variance by variable’ error model which is often fitted using Iteratively Reweighted Least Squares (IRLS) should now be specified as error_model = "obs".
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  • A two-component error model similar to the one proposed by Rocke and Lorenzato can be selected using the argument error_model = "tc".
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+Unique in mkin

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  • Three different error models can be selected using the argument error_model to the mkinfit function. A two-component error model similar to the one proposed by Rocke and Lorenzato can be selected using the argument error_model = "tc".
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  • Model comparisons using the Akaike Information Criterion (AIC) are supported which can also be used for non-constant variance. In such cases the FOCUS chi-squared error level is not meaningful.
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  • 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.
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  • 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 cannot occur in a single experiment with a single defined radiolabel position.
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  • When a metabolite decline phase is not described well by SFO kinetics, SFORB kinetics can be used for the metabolite. Mathematically, the SFORB model is equivalent to the DFOP model used by other tools for biphasic metabolite curves. However, the SFORB model has the advantage that there is a mechanistic interpretation of the model parameters.
  • Nonlinear mixed-effects models can be created from fits of the same degradation model to different datasets for the same compound by using the nlme.mmkin method. Note that the convergence of the nlme fits depends on the quality of the data. Convergence is better for simple models and data for many groups (e.g. soils).
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+Performance

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  • Parallel fitting of several models to several datasets is supported, see for example plot.mmkin.
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  • 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.
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  • Even if no compiler is installed, many degradation models still give very good performance, as current versions of mkin also have analytical solutions for some models with one metabolite, and if SFO or SFORB are used for the parent compound, Eigenvalue based solutions of the degradation model are available.
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GUI

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News

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There is a ChangeLog, for the latest CRAN release and one for the github master branch.

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There is a list of changes for the latest CRAN release and one for each github branch, e.g. the main branch.

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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, among 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.

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.

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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Thanks to René Lehmann, formerly working at the Umweltbundesamt, for the nice cooperation cooperation on parameter transformations, especially the isometric log-ratio transformation that is now used for formation fractions in case there are more than two transformation targets.

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Many inspirations for improvements of mkin resulted from doing kinetic evaluations of degradation data for my clients while working at Harlan Laboratories and at Eurofins Regulatory AG, and now as an independent consultant.

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Funding was received from the Umweltbundesamt in the course of the projects

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  • Grant Number 112407 (Testing and validation of modelling software as an alternative to ModelMaker 4.0, 2014-2015)
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  • Project Number 56703 (Optimization of gmkin for routine use in the Umweltbundesamt, 2015)
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  • Project Number 112407 (Testing the feasibility of using an error model according to Rocke and Lorenzato for more realistic parameter estimates in the kinetic evaluation of degradation data, 2018-2019)
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  • Project Number 120667 (Development of objective criteria for the evaluation of the visual fit in the kinetic evaluation of degradation data, 2019-2020)
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  • Project 146839 (Checking the feasibility of using mixed-effects models for the derivation of kinetic modelling parameters from degradation studies, 2020-2021)
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