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diff --git a/docs/dev/reference/example_analysis/dlls/sforb_sfo2.so b/docs/dev/reference/example_analysis/dlls/sforb_sfo2.so Binary files differnew file mode 100755 index 00000000..a692256d --- /dev/null +++ b/docs/dev/reference/example_analysis/dlls/sforb_sfo2.so diff --git a/docs/dev/reference/example_analysis/example_analysis.Rmd b/docs/dev/reference/example_analysis/example_analysis.Rmd new file mode 100644 index 00000000..38a6bd20 --- /dev/null +++ b/docs/dev/reference/example_analysis/example_analysis.Rmd @@ -0,0 +1,314 @@ +--- +title: "Hierarchical kinetic modelling of degradation data" +author: +date: +output: mkin::hierarchical_kinetics +geometry: margin=2cm +--- + +\clearpage + +# Setup + +```{r packages, cache = FALSE, message = FALSE} +library(mkin) +library(knitr) +library(saemix) +library(parallel) +library(readxl) +``` + +```{r n_cores, cache = FALSE} +n_cores <- detectCores() + +if (Sys.info()["sysname"] == "Windows") { + cl <- makePSOCKcluster(n_cores) +} else { + cl <- makeForkCluster(n_cores) +} +``` + +\clearpage + +# Introduction + +This report shows hierarchical kinetic modelling for ... +The data were obtained from ... + +```{r ds} +data_path <- system.file( + "testdata", "lambda-cyhalothrin_soil_efsa_2014.xlsx", + package = "mkin") +ds <- read_spreadsheet(data_path, valid_datasets = c(1:4, 7:13)) +covariates <- attr(ds, "covariates") +``` + +The covariate data are shown below. + +```{r results = "asis", dependson = "ds", echo = FALSE} +kable(covariates, caption = "Covariate data for all datasets") +``` + +\clearpage + +The datasets with the residue time series are shown in the tables below. Please +refer to the spreadsheet for details like data sources, treatment of values +below reporting limits and time step normalisation factors. + +```{r results = "asis", dependson = "ds", echo = FALSE} +for (ds_name in names(ds)) { + print( + kable(mkin_long_to_wide(ds[[ds_name]]), + caption = paste("Dataset", ds_name), + booktabs = TRUE, row.names = FALSE)) + cat("\n\\clearpage\n") +} +``` + +# Parent only evaluations + +The following code performs separate fits of the candidate degradation models +to all datasets using constant variance and the two-component error model. + +```{r parent-sep, dependson = "ds"} +parent_deg_mods <- c("SFO", "FOMC", "DFOP", "SFORB") +errmods <- c(const = "constant variance", tc = "two-component error") +parent_sep_const <- mmkin( + parent_deg_mods, ds, + error_model = "const", + cluster = cl, quiet = TRUE) +parent_sep_tc <- update(parent_sep_const, error_model = "tc") +``` + +To select the parent model, the corresponding hierarchical fits are performed below. + +```{r parent-mhmkin, dependson = "parent-sep"} +parent_mhmkin <- mhmkin(list(parent_sep_const, parent_sep_tc), cluster = cl) +status(parent_mhmkin) |> kable() +``` + +All fits terminate without errors (status OK). The check for ill-defined +parameters shows that not all random effect parameters can be robustly +quantified. + +```{r dependson = "parent_mhmkin"} +illparms(parent_mhmkin) |> kable() +``` + +Therefore, the fits are updated, excluding random effects that were +ill-defined according to the `illparms` function. The status of the fits +is checked. + +```{r parent-mhmkin-refined} +parent_mhmkin_refined <- update(parent_mhmkin, + no_random_effect = illparms(parent_mhmkin)) +status(parent_mhmkin_refined) |> kable() +``` + +Also, it is checked if the AIC values of the refined fits are actually smaller +than the AIC values of the original fits. + +```{r dependson = "parent-mhmkin-refined"} +(AIC(parent_mhmkin_refined) < AIC(parent_mhmkin)) |> kable() +``` + +From the refined fits, the most suitable model is selected using the AIC. + +```{r parent-best, dependson = "parent-mhmkin"} +aic_parent <- AIC(parent_mhmkin_refined) +min_aic <- which(aic_parent == min(aic_parent), arr.ind = TRUE) +best_degmod_parent <- rownames(aic_parent)[min_aic[1]] +best_errmod_parent <- colnames(aic_parent)[min_aic[2]] +anova(parent_mhmkin_refined) |> kable(digits = 1) +parent_best <- parent_mhmkin_refined[[best_degmod_parent, best_errmod_parent]] +``` + +Based on the AIC, the combination of the `r best_degmod_parent` degradation +model with the error model `r errmods[best_errmod_parent]` is identified to +be most suitable for the degradation of the parent. The check below +confirms that no ill-defined parameters remain for this combined model. + +```{r dependson = "parent-best"} +illparms(parent_best) +``` + +The corresponding fit is plotted below. + +```{r dependson = "parent-best"} +plot(parent_best) +``` +The fitted parameters, together with approximate confidence +intervals are listed below. + +```{r dependson = "parent-best"} +parms(parent_best, ci = TRUE) |> kable(digits = 3) +``` + +To investigate a potential covariate influence on degradation parameters, a +covariate model is added to the hierarchical model for each of the degradation +parameters with well-defined random effects. Also, a version with covariate +models for both of them is fitted. + +```{r parent-best-pH} +parent_best_pH_1 <- update(parent_best, covariates = covariates, + covariate_models = list(log_k_lambda_free ~ pH)) +parent_best_pH_2 <- update(parent_best, covariates = covariates, + covariate_models = list(log_k_lambda_bound_free ~ pH)) +parent_best_pH_3 <- update(parent_best, covariates = covariates, + covariate_models = list(log_k_lambda_free ~ pH, log_k_lambda_bound_free ~ pH)) +``` + +The resulting models are compared. + +```{r dependson = "parent-best-pH"} +anova(parent_best, parent_best_pH_1, parent_best_pH_2, parent_best_pH_3) |> + kable(digits = 1) +``` + +The model fit with the lowest AIC is the one with a pH correlation of the +desorption rate constant `k_lambda_bound_free`. Plot and parameter listing +of this fit are shown below. Also, it is confirmed that no ill-defined +variance parameters are found. + +```{r dependson = "parent-best-pH"} +plot(parent_best_pH_2) +``` + +```{r dependson = "parent-best-pH"} +illparms(parent_best_pH_2) +parms(parent_best_pH_2, ci = TRUE) |> kable(digits = 3) +``` + +\clearpage + +# Pathway fits + +As an example of a pathway fit, a model with SFORB for the parent compound and +parallel formation of two metabolites is set up. + +```{r path-1-degmod} +if (!dir.exists("dlls")) dir.create("dlls") + +m_sforb_sfo2 = mkinmod( + lambda = mkinsub("SFORB", to = c("c_V", "c_XV")), + c_V = mkinsub("SFO"), + c_XV = mkinsub("SFO"), + name = "sforb_sfo2", + dll_dir = "dlls", + overwrite = TRUE, quiet = TRUE +) +``` + +Separate evaluations of all datasets are performed with constant variance +and using two-component error. + +```{r path-1-sep, dependson = c("path-1-degmod", "ds")} +sforb_sep_const <- mmkin(list(sforb_path = m_sforb_sfo2), ds, + cluster = cl, quiet = TRUE) +sforb_sep_tc <- update(sforb_sep_const, error_model = "tc") +``` + +The separate fits with constant variance are plotted. + +```{r dependson = "path-1-sep", fig.height = 9} +plot(mixed(sforb_sep_const)) +``` + +The two corresponding hierarchical fits, with the random effects for the parent +degradation parameters excluded as discussed above, and including the covariate +model that was identified for the parent degradation, are attempted below. + +```{r path-1, dependson = "path-1-sep"} +path_1 <- mhmkin(list(sforb_sep_const, sforb_sep_tc), + no_random_effect = c("lambda_free_0", "log_k_lambda_free_bound"), + covariates = covariates, covariate_models = list(log_k_lambda_bound_free ~ pH), + cluster = cl) +``` + +```{r dependson = "path-1"} +status(path_1) |> kable() +``` + +The status information shows that both fits were successfully completed. + +```{r dependson = "path-1"} +anova(path_1) |> kable(digits = 1) +``` +Model comparison shows that the two-component error model provides a much +better fit. + +```{r dependson = "path-1"} +illparms(path_1[["sforb_path", "tc"]]) +``` + +Two ill-defined variance components are found. Therefore, the fit is +repeated with the corresponding random effects removed. + +```{r path-1-refined, dependson = "path-1"} +path_1_refined <- update(path_1[["sforb_path", "tc"]], + no_random_effect = c("lambda_free_0", "log_k_lambda_free_bound", + "log_k_c_XV", "f_lambda_ilr_2")) +``` + +The empty output of the illparms function indicates that there are no +ill-defined parameters remaining in the refined fit. + +```{r dependson = "path-1-refined"} +illparms(path_1_refined) +``` + +Below, the refined fit is plotted and the fitted parameters are shown together +with their 95% confidence intervals. + +```{r dependson = "path-1-refined", fig.height = 9} +plot(path_1_refined) +``` + +```{r dependson = "path-1-refined", fig.height = 9} +parms(path_1_refined, ci = TRUE) |> kable(digits = 3) +``` + +\clearpage + +# Appendix + +## Listings of initial parent fits + +```{r listings-parent, results = "asis", echo = FALSE, dependson = "parent_mhmkin"} +for (deg_mod in parent_deg_mods) { + for (err_mod in c("const", "tc")) { + caption <- paste("Hierarchical", deg_mod, "fit with", errmods[err_mod]) + tex_listing(parent_mhmkin[[deg_mod, err_mod]], caption) + } +} +``` + +## Listings of refined parent fits + +```{r listings-parent-refined, results = "asis", echo = FALSE, dependson = "parent_mhmkin_refined"} +for (deg_mod in parent_deg_mods) { + for (err_mod in c("const", "tc")) { + caption <- paste("Refined hierarchical", deg_mod, "fit with", errmods[err_mod]) + tex_listing(parent_mhmkin_refined[[deg_mod, err_mod]], caption) + } +} +``` + +## Listings of pathway fits + +```{r listings-path-1, results = "asis", echo = FALSE, dependson = "path-1-refined"} +tex_listing(path_1[["sforb_path", "const"]], + caption = "Hierarchical fit of SFORB-SFO2 with constant variance") +tex_listing(path_1[["sforb_path", "tc"]], + caption = "Hierarchical fit of SFORB-SFO2 with two-component error") +tex_listing(path_1_refined, + caption = "Refined hierarchical fit of SFORB-SFO2 with two-component error") +``` + +## Session info + +```{r echo = FALSE, cache = FALSE} +parallel::stopCluster(cl) +sessionInfo() +``` + diff --git a/docs/dev/reference/example_analysis/header.tex b/docs/dev/reference/example_analysis/header.tex new file mode 100644 index 00000000..a2b7ce83 --- /dev/null +++ b/docs/dev/reference/example_analysis/header.tex @@ -0,0 +1 @@ +\definecolor{shadecolor}{RGB}{248,248,248} diff --git a/docs/dev/reference/example_analysis/skeleton.pdf b/docs/dev/reference/example_analysis/skeleton.pdf Binary files differnew file mode 100644 index 00000000..53c5fb31 --- /dev/null +++ b/docs/dev/reference/example_analysis/skeleton.pdf diff --git a/docs/dev/reference/example_analysis/skeleton_files/figure-latex/unnamed-chunk-11-1.pdf b/docs/dev/reference/example_analysis/skeleton_files/figure-latex/unnamed-chunk-11-1.pdf Binary files differnew file mode 100644 index 00000000..ab685d92 --- /dev/null +++ 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+</li> + </ul><ul class="nav navbar-nav navbar-right"><li> + <a href="https://github.com/jranke/mkin/" class="external-link"> + <span class="fab fa-github fa-lg"></span> + + </a> +</li> + </ul></div><!--/.nav-collapse --> + </div><!--/.container --> +</div><!--/.navbar --> + + + + </header><div class="row"> + <div class="col-md-9 contents"> + <div class="page-header"> + <h1>Hierarchical kinetics template</h1> + <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/R/hierarchical_kinetics.R" class="external-link"><code>R/hierarchical_kinetics.R</code></a></small> + <div class="hidden name"><code>hierarchical_kinetics.Rd</code></div> + </div> + + <div class="ref-description"> + <p>R markdown format for setting up hierarchical kinetics based on a template +provided with the mkin package.</p> + </div> + + <div id="ref-usage"> + <div class="sourceCode"><pre class="sourceCode r"><code><span><span class="fu">hierarchical_kinetics</span><span class="op">(</span><span class="va">...</span>, keep_tex <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span></span></code></pre></div> + </div> + + <div id="arguments"> + <h2>Arguments</h2> + <dl><dt>...</dt> +<dd><p>Arguments to <code><a href="https://pkgs.rstudio.com/rmarkdown/reference/pdf_document.html" class="external-link">rmarkdown::pdf_document</a></code></p></dd> + + +<dt>keep_tex</dt> +<dd><p>Keep the intermediate tex file used in the conversion to PDF</p></dd> + +</dl></div> + <div id="value"> + <h2>Value</h2> + + +<p>R Markdown output format to pass to +<code><a href="https://pkgs.rstudio.com/rmarkdown/reference/render.html" class="external-link">render</a></code></p> + + + </div> + + <div id="ref-examples"> + <h2>Examples</h2> + <div class="sourceCode"><pre class="sourceCode r"><code><span class="r-in"><span></span></span> +<span class="r-in"><span><span class="co"># \dontrun{</span></span></span> +<span class="r-in"><span><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">library</a></span><span class="op">(</span><span class="va"><a href="https://github.com/rstudio/rmarkdown" class="external-link">rmarkdown</a></span><span class="op">)</span></span></span> +<span class="r-in"><span><span class="fu"><a href="https://pkgs.rstudio.com/rmarkdown/reference/draft.html" class="external-link">draft</a></span><span class="op">(</span><span class="st">"example_analysis.rmd"</span>, template <span class="op">=</span> <span class="st">"hierarchical_kinetics"</span>, package <span class="op">=</span> <span class="st">"mkin"</span><span class="op">)</span></span></span> +<span class="r-in"><span><span class="co"># }</span></span></span> +<span class="r-in"><span></span></span> +</code></pre></div> + </div> + </div> + <div class="col-md-3 hidden-xs hidden-sm" id="pkgdown-sidebar"> + <nav id="toc" data-toggle="toc" class="sticky-top"><h2 data-toc-skip>Contents</h2> + </nav></div> +</div> + + + <footer><div class="copyright"> + <p></p><p>Developed by Johannes Ranke.</p> +</div> + +<div class="pkgdown"> + <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.7.</p> +</div> + + </footer></div> + + + + + + + </body></html> + diff --git a/docs/dev/reference/index.html b/docs/dev/reference/index.html index 794126cf..525551fd 100644 --- a/docs/dev/reference/index.html +++ b/docs/dev/reference/index.html @@ -195,6 +195,10 @@ of an mmkin object</p></td> <p class="section-desc"></p><p>Create and work with nonlinear hierarchical models</p> </th> </tr></tbody><tbody><tr><td> + <p><code><a href="hierarchical_kinetics.html">hierarchical_kinetics()</a></code> </p> + </td> + <td><p>Hierarchical kinetics template</p></td> + </tr><tr><td> <p><code><a href="read_spreadsheet.html">read_spreadsheet()</a></code> </p> </td> <td><p>Read datasets and relevant meta information from a spreadsheet file</p></td> @@ -356,9 +360,9 @@ degradation models and one or more error models</p></td> <p class="section-desc"></p> </th> </tr></tbody><tbody><tr><td> - <p><code><a href="tex_listing.html">tex_listing()</a></code> </p> + <p><code><a href="summary_listing.html">summary_listing()</a></code> <code><a href="summary_listing.html">tex_listing()</a></code> <code><a href="summary_listing.html">html_listing()</a></code> </p> </td> - <td><p>Wrap the output of a summary function in tex listing environment</p></td> + <td><p>Display the output of a summary function according to the output format</p></td> </tr><tr><td> <p><code><a href="f_time_norm_focus.html">f_time_norm_focus()</a></code> </p> </td> @@ -493,7 +497,7 @@ kinetic models fitted with mkinfit</p></td> </div> <div class="pkgdown"> - <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.6.</p> + <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.7.</p> </div> </footer></div> diff --git a/docs/dev/reference/mkinmod.html b/docs/dev/reference/mkinmod.html index 251215a7..145dee83 100644 --- a/docs/dev/reference/mkinmod.html +++ b/docs/dev/reference/mkinmod.html @@ -132,7 +132,7 @@ the source compartment. Additionally, <code>mkinsub()</code> has an argument <code>to</code>, specifying names of variables to which a transfer is to be assumed in the model. If the argument <code>use_of_ff</code> is set to "min" -(default) and the model for the compartment is "SFO" or "SFORB", an +and the model for the compartment is "SFO" or "SFORB", an additional <code>mkinsub()</code> argument can be <code>sink = FALSE</code>, effectively fixing the flux to sink to zero. In print.mkinmod, this argument is currently not used.</p></dd> @@ -247,7 +247,7 @@ in the FOCUS and NAFTA guidance documents are used.</p> <p>For kinetic models with more than one observed variable, a symbolic solution of the system of differential equations is included in the resulting mkinmod object in some cases, speeding up the solution.</p> -<p>If a C compiler is found by <code><a href="https://rdrr.io/pkg/pkgbuild/man/has_compiler.html" class="external-link">pkgbuild::has_compiler()</a></code> and there +<p>If a C compiler is found by <code><a href="https://r-lib.github.io/pkgbuild/reference/has_compiler.html" class="external-link">pkgbuild::has_compiler()</a></code> and there is more than one observed variable in the specification, C code is generated for evaluating the differential equations, compiled using <code><a href="https://rdrr.io/pkg/inline/man/cfunction.html" class="external-link">inline::cfunction()</a></code> and added to the resulting mkinmod object.</p> @@ -310,7 +310,7 @@ Evaluating and Calculating Degradation Kinetics in Environmental Media</p> <span class="r-in"><span> parent <span class="op">=</span> <span class="fu">mkinsub</span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"m1"</span>, full_name <span class="op">=</span> <span class="st">"Test compound"</span><span class="op">)</span>,</span></span> <span class="r-in"><span> m1 <span class="op">=</span> <span class="fu">mkinsub</span><span class="op">(</span><span class="st">"SFO"</span>, full_name <span class="op">=</span> <span class="st">"Metabolite M1"</span><span class="op">)</span>,</span></span> <span class="r-in"><span> name <span class="op">=</span> <span class="st">"SFO_SFO"</span>, dll_dir <span class="op">=</span> <span class="va">DLL_dir</span>, unload <span class="op">=</span> <span class="cn">TRUE</span>, overwrite <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span></span> -<span class="r-msg co"><span class="r-pr">#></span> Copied DLL from /tmp/RtmpbZbZ8Y/file8c6a9f402f42.so to /home/jranke/.local/share/mkin/SFO_SFO.so</span> +<span class="r-msg co"><span class="r-pr">#></span> Copied DLL from /tmp/RtmpelWAOB/fileb43c31a25a86.so to /home/jranke/.local/share/mkin/SFO_SFO.so</span> <span class="r-in"><span><span class="co"># Now we can save the model and restore it in a new session</span></span></span> <span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/readRDS.html" class="external-link">saveRDS</a></span><span class="op">(</span><span class="va">SFO_SFO.2</span>, file <span class="op">=</span> <span class="st">"~/SFO_SFO.rds"</span><span class="op">)</span></span></span> <span class="r-in"><span><span class="co"># Terminate the R session here if you would like to check, and then do</span></span></span> @@ -363,7 +363,7 @@ Evaluating and Calculating Degradation Kinetics in Environmental Media</p> <span class="r-out co"><span class="r-pr">#></span> })</span> <span class="r-out co"><span class="r-pr">#></span> return(predicted)</span> <span class="r-out co"><span class="r-pr">#></span> }</span> -<span class="r-out co"><span class="r-pr">#></span> <environment: 0x55556029f678></span> +<span class="r-out co"><span class="r-pr">#></span> <environment: 0x55555f013820></span> <span class="r-in"><span></span></span> <span class="r-in"><span><span class="co"># If we have several parallel metabolites</span></span></span> <span class="r-in"><span><span class="co"># (compare tests/testthat/test_synthetic_data_for_UBA_2014.R)</span></span></span> @@ -392,7 +392,7 @@ Evaluating and Calculating Degradation Kinetics in Environmental Media</p> </div> <div class="pkgdown"> - <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.6.</p> + <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.7.</p> </div> </footer></div> diff --git 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<span class="fab fa-github fa-lg"></span> + + </a> +</li> + </ul></div><!--/.nav-collapse --> + </div><!--/.container --> +</div><!--/.navbar --> + + + + </header><div class="row"> + <div class="col-md-9 contents"> + <div class="page-header"> + <h1>Display the output of a summary function according to the output format</h1> + <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/R/summary_listing.R" class="external-link"><code>R/summary_listing.R</code></a></small> + <div class="hidden name"><code>summary_listing.Rd</code></div> + </div> + + <div class="ref-description"> + <p>This function is intended for use in a R markdown code chunk with the chunk +option <code>results = "asis"</code>.</p> + </div> + + <div id="ref-usage"> + <div class="sourceCode"><pre class="sourceCode r"><code><span><span class="fu">summary_listing</span><span class="op">(</span><span class="va">object</span>, caption <span class="op">=</span> <span class="cn">NULL</span>, label <span class="op">=</span> <span class="cn">NULL</span>, clearpage <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span> +<span></span> +<span><span class="fu">tex_listing</span><span class="op">(</span><span class="va">object</span>, caption <span class="op">=</span> <span class="cn">NULL</span>, label <span class="op">=</span> <span class="cn">NULL</span>, clearpage <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span> +<span></span> +<span><span class="fu">html_listing</span><span class="op">(</span><span class="va">object</span>, caption <span class="op">=</span> <span class="cn">NULL</span><span class="op">)</span></span></code></pre></div> + </div> + + <div id="arguments"> + <h2>Arguments</h2> + <dl><dt>object</dt> +<dd><p>The object for which the summary is to be listed</p></dd> + + +<dt>caption</dt> +<dd><p>An optional caption</p></dd> + + +<dt>label</dt> +<dd><p>An optional label, ignored in html output</p></dd> + + +<dt>clearpage</dt> +<dd><p>Should a new page be started after the listing? Ignored in html output</p></dd> + +</dl></div> + + </div> + <div class="col-md-3 hidden-xs hidden-sm" id="pkgdown-sidebar"> + <nav id="toc" data-toggle="toc" class="sticky-top"><h2 data-toc-skip>Contents</h2> + </nav></div> +</div> + + + <footer><div class="copyright"> + <p></p><p>Developed by Johannes Ranke.</p> +</div> + +<div class="pkgdown"> + <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.7.</p> +</div> + + </footer></div> + + + + + + + </body></html> + |