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class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/vignettes/prebuilt/2022_dmta_pathway.rmd" class="external-link"><code>vignettes/prebuilt/2022_dmta_pathway.rmd</code></a></small> <div class="hidden name"><code>2022_dmta_pathway.rmd</code></div> </div> <div class="section level2"> <h2 id="introduction">Introduction<a class="anchor" aria-label="anchor" href="#introduction"></a> </h2> <p>The purpose of this document is to test demonstrate how nonlinear hierarchical models (NLHM) based on the parent degradation models SFO, FOMC, DFOP and HS, with parallel formation of two or more metabolites can be fitted with the mkin package.</p> <p>It was assembled in the course of work package 1.2 of Project Number 173340 (Application of nonlinear hierarchical models to the kinetic evaluation of chemical degradation data) of the German Environment Agency carried out in 2022 and 2023.</p> <p>The mkin package is used in version 1.2.3, which is currently under development. It contains the test data, and the functions used in the evaluations. The <code>saemix</code> package is used as a backend for fitting the NLHM, but is also loaded to make the convergence plot function available.</p> <p>This document is processed with the <code>knitr</code> package, which also provides the <code>kable</code> function that is used to improve the display of tabular data in R markdown documents. For parallel processing, the <code>parallel</code> package is used.</p> <div class="sourceCode" id="cb1"><pre class="downlit sourceCode r"> <code class="sourceCode R"><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://pkgdown.jrwb.de/mkin/">mkin</a></span><span class="op">)</span></span> <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://yihui.org/knitr/" class="external-link">knitr</a></span><span class="op">)</span></span> <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">saemix</span><span class="op">)</span></span> <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">parallel</span><span class="op">)</span></span> <span><span class="va">n_cores</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/parallel/detectCores.html" class="external-link">detectCores</a></span><span class="op">(</span><span class="op">)</span></span> <span><span class="kw">if</span> <span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/Sys.info.html" class="external-link">Sys.info</a></span><span class="op">(</span><span class="op">)</span><span class="op">[</span><span class="st">"sysname"</span><span class="op">]</span> <span class="op">==</span> <span class="st">"Windows"</span><span class="op">)</span> <span class="op">{</span></span> <span> <span class="va">cl</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/parallel/makeCluster.html" class="external-link">makePSOCKcluster</a></span><span class="op">(</span><span class="va">n_cores</span><span class="op">)</span></span> <span><span class="op">}</span> <span class="kw">else</span> <span class="op">{</span></span> <span> <span class="va">cl</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/parallel/makeCluster.html" class="external-link">makeForkCluster</a></span><span class="op">(</span><span class="va">n_cores</span><span class="op">)</span></span> <span><span class="op">}</span></span></code></pre></div> </div> <div class="section level2"> <h2 id="data">Data<a class="anchor" aria-label="anchor" href="#data"></a> </h2> <p>The test data are available in the mkin package as an object of class <code>mkindsg</code> (mkin dataset group) under the identifier <code>dimethenamid_2018</code>. The following preprocessing steps are done in this document.</p> <ul> <li>The data available for the enantiomer dimethenamid-P (DMTAP) are renamed to have the same substance name as the data for the racemic mixture dimethenamid (DMTA). The reason for this is that no difference between their degradation behaviour was identified in the EU risk assessment.</li> <li>Unnecessary columns are discarded</li> <li>The observation times of each dataset are multiplied with the corresponding normalisation factor also available in the dataset, in order to make it possible to describe all datasets with a single set of parameters that are independent of temperature</li> <li>Finally, datasets observed in the same soil (<code>Elliot 1</code> and <code>Elliot 2</code>) are combined, resulting in dimethenamid (DMTA) data from six soils.</li> </ul> <p>The following commented R code performs this preprocessing.</p> <div class="sourceCode" id="cb2"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="co"># Apply a function to each of the seven datasets in the mkindsg object to create a list</span></span> <span><span class="va">dmta_ds</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">lapply</a></span><span class="op">(</span><span class="fl">1</span><span class="op">:</span><span class="fl">7</span>, <span class="kw">function</span><span class="op">(</span><span class="va">i</span><span class="op">)</span> <span class="op">{</span></span> <span> <span class="va">ds_i</span> <span class="op"><-</span> <span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">ds</span><span class="op">[[</span><span class="va">i</span><span class="op">]</span><span class="op">]</span><span class="op">$</span><span class="va">data</span> <span class="co"># Get a dataset</span></span> <span> <span class="va">ds_i</span><span class="op">[</span><span class="va">ds_i</span><span class="op">$</span><span class="va">name</span> <span class="op">==</span> <span class="st">"DMTAP"</span>, <span class="st">"name"</span><span class="op">]</span> <span class="op"><-</span> <span class="st">"DMTA"</span> <span class="co"># Rename DMTAP to DMTA</span></span> <span> <span class="va">ds_i</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/subset.html" class="external-link">subset</a></span><span class="op">(</span><span class="va">ds_i</span>, select <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"name"</span>, <span class="st">"time"</span>, <span class="st">"value"</span><span class="op">)</span><span class="op">)</span> <span class="co"># Select data</span></span> <span> <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op"><-</span> <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op">*</span> <span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">f_time_norm</span><span class="op">[</span><span class="va">i</span><span class="op">]</span> <span class="co"># Normalise time</span></span> <span> <span class="va">ds_i</span> <span class="co"># Return the dataset</span></span> <span><span class="op">}</span><span class="op">)</span></span> <span></span> <span><span class="co"># Use dataset titles as names for the list elements</span></span> <span><span class="fu"><a href="https://rdrr.io/r/base/names.html" class="external-link">names</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">)</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">ds</span>, <span class="kw">function</span><span class="op">(</span><span class="va">ds</span><span class="op">)</span> <span class="va">ds</span><span class="op">$</span><span class="va">title</span><span class="op">)</span></span> <span></span> <span><span class="co"># Combine data for Elliot soil to obtain a named list with six elements</span></span> <span><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/cbind.html" class="external-link">rbind</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 1"</span><span class="op">]</span><span class="op">]</span>, <span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 2"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span> <span class="co">#</span></span> <span><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 1"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="cn">NULL</span></span> <span><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 2"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="cn">NULL</span></span></code></pre></div> <p>The following tables show the 6 datasets.</p> <div class="sourceCode" id="cb3"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="kw">for</span> <span class="op">(</span><span class="va">ds_name</span> <span class="kw">in</span> <span class="fu"><a href="https://rdrr.io/r/base/names.html" class="external-link">names</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">)</span><span class="op">)</span> <span class="op">{</span></span> <span> <span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span></span> <span> <span class="fu"><a href="https://rdrr.io/pkg/knitr/man/kable.html" class="external-link">kable</a></span><span class="op">(</span><span class="fu"><a href="../../reference/mkin_long_to_wide.html">mkin_long_to_wide</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">[[</span><span class="va">ds_name</span><span class="op">]</span><span class="op">]</span><span class="op">)</span>,</span> <span> caption <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/paste.html" class="external-link">paste</a></span><span class="op">(</span><span class="st">"Dataset"</span>, <span class="va">ds_name</span><span class="op">)</span>,</span> <span> booktabs <span class="op">=</span> <span class="cn">TRUE</span>, row.names <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span><span class="op">)</span></span> <span> <span class="fu"><a href="https://rdrr.io/r/base/cat.html" class="external-link">cat</a></span><span class="op">(</span><span class="st">"\n\\clearpage\n"</span><span class="op">)</span></span> <span><span class="op">}</span></span></code></pre></div> <table class="table"> <caption>Dataset Calke</caption> <thead><tr class="header"> <th align="right">time</th> <th align="right">DMTA</th> <th align="right">M23</th> <th align="right">M27</th> <th align="right">M31</th> </tr></thead> <tbody> <tr class="odd"> <td align="right">0</td> <td align="right">95.8</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">0</td> <td align="right">98.7</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="odd"> <td align="right">14</td> <td align="right">60.5</td> <td align="right">4.1</td> <td align="right">1.5</td> <td align="right">2.0</td> </tr> <tr class="even"> <td align="right">30</td> <td align="right">39.1</td> <td align="right">5.3</td> <td align="right">2.4</td> <td align="right">2.1</td> </tr> <tr class="odd"> <td align="right">59</td> <td align="right">15.2</td> <td align="right">6.0</td> <td align="right">3.2</td> <td align="right">2.2</td> </tr> <tr class="even"> <td align="right">120</td> <td align="right">4.8</td> <td align="right">4.3</td> <td align="right">3.8</td> <td align="right">1.8</td> </tr> <tr class="odd"> <td align="right">120</td> <td align="right">4.6</td> <td align="right">4.1</td> <td align="right">3.7</td> <td align="right">2.1</td> </tr> </tbody> </table> <table class="table"> <caption>Dataset Borstel</caption> <thead><tr class="header"> <th align="right">time</th> <th align="right">DMTA</th> <th align="right">M23</th> <th align="right">M27</th> <th align="right">M31</th> </tr></thead> <tbody> <tr class="odd"> <td align="right">0.000000</td> <td align="right">100.5</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">0.000000</td> <td align="right">99.6</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="odd"> <td align="right">1.941295</td> <td align="right">91.9</td> <td align="right">0.4</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">1.941295</td> <td align="right">91.3</td> <td align="right">0.5</td> <td align="right">0.3</td> <td align="right">0.1</td> </tr> <tr class="odd"> <td align="right">6.794534</td> <td align="right">81.8</td> <td align="right">1.2</td> <td align="right">0.8</td> <td align="right">1.0</td> </tr> <tr class="even"> <td align="right">6.794534</td> <td align="right">82.1</td> <td align="right">1.3</td> <td align="right">0.9</td> <td align="right">0.9</td> </tr> <tr class="odd"> <td align="right">13.589067</td> <td align="right">69.1</td> <td align="right">2.8</td> <td align="right">1.4</td> <td align="right">2.0</td> </tr> <tr class="even"> <td align="right">13.589067</td> <td align="right">68.0</td> <td align="right">2.0</td> <td align="right">1.4</td> <td align="right">2.5</td> </tr> <tr class="odd"> <td align="right">27.178135</td> <td align="right">51.4</td> <td align="right">2.9</td> <td align="right">2.7</td> <td align="right">4.3</td> </tr> <tr class="even"> <td align="right">27.178135</td> <td align="right">51.4</td> <td align="right">4.9</td> <td align="right">2.6</td> <td align="right">3.2</td> </tr> <tr class="odd"> <td align="right">56.297565</td> <td align="right">27.6</td> <td align="right">12.2</td> <td align="right">4.4</td> <td align="right">4.3</td> </tr> <tr class="even"> <td align="right">56.297565</td> <td align="right">26.8</td> <td align="right">12.2</td> <td align="right">4.7</td> <td align="right">4.8</td> </tr> <tr class="odd"> <td align="right">86.387643</td> <td align="right">15.7</td> <td align="right">12.2</td> <td align="right">5.4</td> <td align="right">5.0</td> </tr> <tr class="even"> <td align="right">86.387643</td> <td align="right">15.3</td> <td align="right">12.0</td> <td align="right">5.2</td> <td align="right">5.1</td> </tr> <tr class="odd"> <td align="right">115.507073</td> <td align="right">7.9</td> <td align="right">10.4</td> <td align="right">5.4</td> <td align="right">4.3</td> </tr> <tr class="even"> <td align="right">115.507073</td> <td align="right">8.1</td> <td align="right">11.6</td> <td align="right">5.4</td> <td align="right">4.4</td> </tr> </tbody> </table> <table class="table"> <caption>Dataset Flaach</caption> <thead><tr class="header"> <th align="right">time</th> <th align="right">DMTA</th> <th align="right">M23</th> <th align="right">M27</th> <th align="right">M31</th> </tr></thead> <tbody> <tr class="odd"> <td align="right">0.0000000</td> <td align="right">96.5</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">0.0000000</td> <td align="right">96.8</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="odd"> <td align="right">0.0000000</td> <td align="right">97.0</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">0.6233856</td> <td align="right">82.9</td> <td align="right">0.7</td> <td align="right">1.1</td> <td align="right">0.3</td> </tr> <tr class="odd"> <td align="right">0.6233856</td> <td align="right">86.7</td> <td align="right">0.7</td> <td align="right">1.1</td> <td align="right">0.3</td> </tr> <tr class="even"> <td align="right">0.6233856</td> <td align="right">87.4</td> <td align="right">0.2</td> <td align="right">0.3</td> <td align="right">0.1</td> </tr> <tr class="odd"> <td align="right">1.8701567</td> <td align="right">72.8</td> <td align="right">2.2</td> <td align="right">2.6</td> <td align="right">0.7</td> </tr> <tr class="even"> <td align="right">1.8701567</td> <td align="right">69.9</td> <td align="right">1.8</td> <td align="right">2.4</td> <td align="right">0.6</td> </tr> <tr class="odd"> <td align="right">1.8701567</td> <td align="right">71.9</td> <td align="right">1.6</td> <td align="right">2.3</td> <td align="right">0.7</td> </tr> <tr class="even"> <td align="right">4.3636989</td> <td align="right">51.4</td> <td align="right">4.1</td> <td align="right">5.0</td> <td align="right">1.3</td> </tr> <tr class="odd"> <td align="right">4.3636989</td> <td align="right">52.9</td> <td align="right">4.2</td> <td align="right">5.9</td> <td align="right">1.2</td> </tr> <tr class="even"> <td align="right">4.3636989</td> <td align="right">48.6</td> <td align="right">4.2</td> <td align="right">4.8</td> <td align="right">1.4</td> </tr> <tr class="odd"> <td align="right">8.7273979</td> <td align="right">28.5</td> <td align="right">7.5</td> <td align="right">8.5</td> <td align="right">2.4</td> </tr> <tr class="even"> <td align="right">8.7273979</td> <td align="right">27.3</td> <td align="right">7.1</td> <td align="right">8.5</td> <td align="right">2.1</td> </tr> <tr class="odd"> <td align="right">8.7273979</td> <td align="right">27.5</td> <td align="right">7.5</td> <td align="right">8.3</td> <td align="right">2.3</td> </tr> <tr class="even"> <td align="right">13.0910968</td> <td align="right">14.8</td> <td align="right">8.4</td> <td align="right">9.3</td> <td align="right">3.3</td> </tr> <tr class="odd"> <td align="right">13.0910968</td> <td align="right">13.4</td> <td align="right">6.8</td> <td align="right">8.7</td> <td align="right">2.4</td> </tr> <tr class="even"> <td align="right">13.0910968</td> <td align="right">14.4</td> <td align="right">8.0</td> <td align="right">9.1</td> <td align="right">2.6</td> </tr> <tr class="odd"> <td align="right">17.4547957</td> <td align="right">7.7</td> <td align="right">7.2</td> <td align="right">8.6</td> <td align="right">4.0</td> </tr> <tr class="even"> <td align="right">17.4547957</td> <td align="right">7.3</td> <td align="right">7.2</td> <td align="right">8.5</td> <td align="right">3.6</td> </tr> <tr class="odd"> <td align="right">17.4547957</td> <td align="right">8.1</td> <td align="right">6.9</td> <td align="right">8.9</td> <td align="right">3.3</td> </tr> <tr class="even"> <td align="right">26.1821936</td> <td align="right">2.0</td> <td align="right">4.9</td> <td align="right">8.1</td> <td align="right">2.1</td> </tr> <tr class="odd"> <td align="right">26.1821936</td> <td align="right">1.5</td> <td align="right">4.3</td> <td align="right">7.7</td> <td align="right">1.7</td> </tr> <tr class="even"> <td align="right">26.1821936</td> <td align="right">1.9</td> <td align="right">4.5</td> <td align="right">7.4</td> <td align="right">1.8</td> </tr> <tr class="odd"> <td align="right">34.9095915</td> <td align="right">1.3</td> <td align="right">3.8</td> <td align="right">5.9</td> <td align="right">1.6</td> </tr> <tr class="even"> <td align="right">34.9095915</td> <td align="right">1.0</td> <td align="right">3.1</td> <td align="right">6.0</td> <td align="right">1.6</td> </tr> <tr class="odd"> <td align="right">34.9095915</td> <td align="right">1.1</td> <td align="right">3.1</td> <td align="right">5.9</td> <td align="right">1.4</td> </tr> <tr class="even"> <td align="right">43.6369893</td> <td align="right">0.9</td> <td align="right">2.7</td> <td align="right">5.6</td> <td align="right">1.8</td> </tr> <tr class="odd"> <td align="right">43.6369893</td> <td align="right">0.7</td> <td align="right">2.3</td> <td align="right">5.2</td> <td align="right">1.5</td> </tr> <tr class="even"> <td align="right">43.6369893</td> <td align="right">0.7</td> <td align="right">2.1</td> <td align="right">5.6</td> <td align="right">1.3</td> </tr> <tr class="odd"> <td align="right">52.3643872</td> <td align="right">0.6</td> <td align="right">1.6</td> <td align="right">4.3</td> <td align="right">1.2</td> </tr> <tr class="even"> <td align="right">52.3643872</td> <td align="right">0.4</td> <td align="right">1.1</td> <td align="right">3.7</td> <td align="right">0.9</td> </tr> <tr class="odd"> <td align="right">52.3643872</td> <td align="right">0.5</td> <td align="right">1.3</td> <td align="right">3.9</td> <td align="right">1.1</td> </tr> <tr class="even"> <td align="right">74.8062674</td> <td align="right">0.4</td> <td align="right">0.4</td> <td align="right">2.5</td> <td align="right">0.5</td> </tr> <tr class="odd"> <td align="right">74.8062674</td> <td align="right">0.3</td> <td align="right">0.4</td> <td align="right">2.4</td> <td align="right">0.5</td> </tr> <tr class="even"> <td align="right">74.8062674</td> <td align="right">0.3</td> <td align="right">0.3</td> <td align="right">2.2</td> <td align="right">0.3</td> </tr> </tbody> </table> <table class="table"> <caption>Dataset BBA 2.2</caption> <thead><tr class="header"> <th align="right">time</th> <th align="right">DMTA</th> <th align="right">M23</th> <th align="right">M27</th> <th align="right">M31</th> </tr></thead> <tbody> <tr class="odd"> <td align="right">0.0000000</td> <td align="right">98.09</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">0.0000000</td> <td align="right">98.77</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="odd"> <td align="right">0.7678922</td> <td align="right">93.52</td> <td align="right">0.36</td> <td align="right">0.42</td> <td align="right">0.36</td> </tr> <tr class="even"> <td align="right">0.7678922</td> <td align="right">92.03</td> <td align="right">0.40</td> <td align="right">0.47</td> <td align="right">0.33</td> </tr> <tr class="odd"> <td align="right">2.3036765</td> <td align="right">88.39</td> <td align="right">1.03</td> <td align="right">0.71</td> <td align="right">0.55</td> </tr> <tr class="even"> <td align="right">2.3036765</td> <td align="right">87.18</td> <td align="right">1.07</td> <td align="right">0.82</td> <td align="right">0.64</td> </tr> <tr class="odd"> <td align="right">5.3752452</td> <td align="right">69.38</td> <td align="right">3.60</td> <td align="right">2.19</td> <td align="right">1.94</td> </tr> <tr class="even"> <td align="right">5.3752452</td> <td align="right">71.06</td> <td align="right">3.66</td> <td align="right">2.28</td> <td align="right">1.62</td> </tr> <tr class="odd"> <td align="right">10.7504904</td> <td align="right">45.21</td> <td align="right">6.97</td> <td align="right">5.45</td> <td align="right">4.22</td> </tr> <tr class="even"> <td align="right">10.7504904</td> <td align="right">46.81</td> <td align="right">7.22</td> <td align="right">5.19</td> <td align="right">4.37</td> </tr> <tr class="odd"> <td align="right">16.1257355</td> <td align="right">30.54</td> <td align="right">8.65</td> <td align="right">8.81</td> <td align="right">6.31</td> </tr> <tr class="even"> <td align="right">16.1257355</td> <td align="right">30.07</td> <td align="right">8.38</td> <td align="right">7.93</td> <td align="right">6.85</td> </tr> <tr class="odd"> <td align="right">21.5009807</td> <td align="right">21.60</td> <td align="right">9.10</td> <td align="right">10.25</td> <td align="right">7.05</td> </tr> <tr class="even"> <td align="right">21.5009807</td> <td align="right">20.41</td> <td align="right">8.63</td> <td align="right">10.77</td> <td align="right">6.84</td> </tr> <tr class="odd"> <td align="right">32.2514711</td> <td align="right">9.10</td> <td align="right">7.63</td> <td align="right">10.89</td> <td align="right">6.53</td> </tr> <tr class="even"> <td align="right">32.2514711</td> <td align="right">9.70</td> <td align="right">8.01</td> <td align="right">10.85</td> <td align="right">7.11</td> </tr> <tr class="odd"> <td align="right">43.0019614</td> <td align="right">6.58</td> <td align="right">6.40</td> <td align="right">10.41</td> <td align="right">6.06</td> </tr> <tr class="even"> <td align="right">43.0019614</td> <td align="right">6.31</td> <td align="right">6.35</td> <td align="right">10.35</td> <td align="right">6.05</td> </tr> <tr class="odd"> <td align="right">53.7524518</td> <td align="right">3.47</td> <td align="right">5.35</td> <td align="right">9.92</td> <td align="right">5.50</td> </tr> <tr class="even"> <td align="right">53.7524518</td> <td align="right">3.52</td> <td align="right">5.06</td> <td align="right">9.42</td> <td align="right">5.07</td> </tr> <tr class="odd"> <td align="right">64.5029421</td> <td align="right">3.40</td> <td align="right">5.14</td> <td align="right">9.15</td> <td align="right">4.94</td> </tr> <tr class="even"> <td align="right">64.5029421</td> <td align="right">3.67</td> <td align="right">5.91</td> <td align="right">9.25</td> <td align="right">4.39</td> </tr> <tr class="odd"> <td align="right">91.3791680</td> <td align="right">1.62</td> <td align="right">3.35</td> <td align="right">7.14</td> <td align="right">3.64</td> </tr> <tr class="even"> <td align="right">91.3791680</td> <td align="right">1.62</td> <td align="right">2.87</td> <td align="right">7.13</td> <td align="right">3.55</td> </tr> </tbody> </table> <table class="table"> <caption>Dataset BBA 2.3</caption> <thead><tr class="header"> <th align="right">time</th> <th align="right">DMTA</th> <th align="right">M23</th> <th align="right">M27</th> <th align="right">M31</th> </tr></thead> <tbody> <tr class="odd"> <td align="right">0.0000000</td> <td align="right">99.33</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">0.0000000</td> <td align="right">97.44</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="odd"> <td align="right">0.6733938</td> <td align="right">93.73</td> <td align="right">0.18</td> <td align="right">0.50</td> <td align="right">0.47</td> </tr> <tr class="even"> <td align="right">0.6733938</td> <td align="right">93.77</td> <td align="right">0.18</td> <td align="right">0.83</td> <td align="right">0.34</td> </tr> <tr class="odd"> <td align="right">2.0201814</td> <td align="right">87.84</td> <td align="right">0.52</td> <td align="right">1.25</td> <td align="right">1.00</td> </tr> <tr class="even"> <td align="right">2.0201814</td> <td align="right">89.82</td> <td align="right">0.43</td> <td align="right">1.09</td> <td align="right">0.89</td> </tr> <tr class="odd"> <td align="right">4.7137565</td> <td align="right">71.61</td> <td align="right">1.19</td> <td align="right">3.28</td> <td align="right">3.58</td> </tr> <tr class="even"> <td align="right">4.7137565</td> <td align="right">71.42</td> <td align="right">1.11</td> <td align="right">3.24</td> <td align="right">3.41</td> </tr> <tr class="odd"> <td align="right">9.4275131</td> <td align="right">45.60</td> <td align="right">2.26</td> <td align="right">7.17</td> <td align="right">8.74</td> </tr> <tr class="even"> <td align="right">9.4275131</td> <td align="right">45.42</td> <td align="right">1.99</td> <td align="right">7.91</td> <td align="right">8.28</td> </tr> <tr class="odd"> <td align="right">14.1412696</td> <td align="right">31.12</td> <td align="right">2.81</td> <td align="right">10.15</td> <td align="right">9.67</td> </tr> <tr class="even"> <td align="right">14.1412696</td> <td align="right">31.68</td> <td align="right">2.83</td> <td align="right">9.55</td> <td align="right">8.95</td> </tr> <tr class="odd"> <td align="right">18.8550262</td> <td align="right">23.20</td> <td align="right">3.39</td> <td align="right">12.09</td> <td align="right">10.34</td> </tr> <tr class="even"> <td align="right">18.8550262</td> <td align="right">24.13</td> <td align="right">3.56</td> <td align="right">11.89</td> <td align="right">10.00</td> </tr> <tr class="odd"> <td align="right">28.2825393</td> <td align="right">9.43</td> <td align="right">3.49</td> <td align="right">13.32</td> <td align="right">7.89</td> </tr> <tr class="even"> <td align="right">28.2825393</td> <td align="right">9.82</td> <td align="right">3.28</td> <td align="right">12.05</td> <td align="right">8.13</td> </tr> <tr class="odd"> <td align="right">37.7100523</td> <td align="right">7.08</td> <td align="right">2.80</td> <td align="right">10.04</td> <td align="right">5.06</td> </tr> <tr class="even"> <td align="right">37.7100523</td> <td align="right">8.64</td> <td align="right">2.97</td> <td align="right">10.78</td> <td align="right">5.54</td> </tr> <tr class="odd"> <td align="right">47.1375654</td> <td align="right">4.41</td> <td align="right">2.42</td> <td align="right">9.32</td> <td align="right">3.79</td> </tr> <tr class="even"> <td align="right">47.1375654</td> <td align="right">4.78</td> <td align="right">2.51</td> <td align="right">9.62</td> <td align="right">4.11</td> </tr> <tr class="odd"> <td align="right">56.5650785</td> <td align="right">4.92</td> <td align="right">2.22</td> <td align="right">8.00</td> <td align="right">3.11</td> </tr> <tr class="even"> <td align="right">56.5650785</td> <td align="right">5.08</td> <td align="right">1.95</td> <td align="right">8.45</td> <td align="right">2.98</td> </tr> <tr class="odd"> <td align="right">80.1338612</td> <td align="right">2.13</td> <td align="right">1.28</td> <td align="right">5.71</td> <td align="right">1.78</td> </tr> <tr class="even"> <td align="right">80.1338612</td> <td align="right">2.23</td> <td align="right">0.99</td> <td align="right">3.33</td> <td align="right">1.55</td> </tr> </tbody> </table> <table class="table"> <caption>Dataset Elliot</caption> <thead><tr class="header"> <th align="right">time</th> <th align="right">DMTA</th> <th align="right">M23</th> <th align="right">M27</th> <th align="right">M31</th> </tr></thead> <tbody> <tr class="odd"> <td align="right">0.000000</td> <td align="right">97.5</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">0.000000</td> <td align="right">100.7</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="odd"> <td align="right">1.228478</td> <td align="right">86.4</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">1.228478</td> <td align="right">88.5</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">1.5</td> </tr> <tr class="odd"> <td align="right">3.685435</td> <td align="right">69.8</td> <td align="right">2.8</td> <td align="right">2.3</td> <td align="right">5.0</td> </tr> <tr class="even"> <td align="right">3.685435</td> <td align="right">77.1</td> <td align="right">1.7</td> <td align="right">2.1</td> <td align="right">2.4</td> </tr> <tr class="odd"> <td align="right">8.599349</td> <td align="right">59.0</td> <td align="right">4.3</td> <td align="right">4.0</td> <td align="right">4.3</td> </tr> <tr class="even"> <td align="right">8.599349</td> <td align="right">54.2</td> <td align="right">5.8</td> <td align="right">3.4</td> <td align="right">5.0</td> </tr> <tr class="odd"> <td align="right">17.198697</td> <td align="right">31.3</td> <td align="right">8.2</td> <td align="right">6.6</td> <td align="right">8.0</td> </tr> <tr class="even"> <td align="right">17.198697</td> <td align="right">33.5</td> <td align="right">5.2</td> <td align="right">6.9</td> <td align="right">7.7</td> </tr> <tr class="odd"> <td align="right">25.798046</td> <td align="right">19.6</td> <td align="right">5.1</td> <td align="right">8.2</td> <td align="right">7.8</td> </tr> <tr class="even"> <td align="right">25.798046</td> <td align="right">20.9</td> <td align="right">6.1</td> <td align="right">8.8</td> <td align="right">6.5</td> </tr> <tr class="odd"> <td align="right">34.397395</td> <td align="right">13.3</td> <td align="right">6.0</td> <td align="right">9.7</td> <td align="right">8.0</td> </tr> <tr class="even"> <td align="right">34.397395</td> <td align="right">15.8</td> <td align="right">6.0</td> <td align="right">8.8</td> <td align="right">7.4</td> </tr> <tr class="odd"> <td align="right">51.596092</td> <td align="right">6.7</td> <td align="right">5.0</td> <td align="right">8.3</td> <td align="right">6.9</td> </tr> <tr class="even"> <td align="right">51.596092</td> <td align="right">8.7</td> <td align="right">4.2</td> <td align="right">9.2</td> <td align="right">9.0</td> </tr> <tr class="odd"> <td align="right">68.794789</td> <td align="right">8.8</td> <td align="right">3.9</td> <td align="right">9.3</td> <td align="right">5.5</td> </tr> <tr class="even"> <td align="right">68.794789</td> <td align="right">8.7</td> <td align="right">2.9</td> <td align="right">8.5</td> <td align="right">6.1</td> </tr> <tr class="odd"> <td align="right">103.192184</td> <td align="right">6.0</td> <td align="right">1.9</td> <td align="right">8.6</td> <td align="right">6.1</td> </tr> <tr class="even"> <td align="right">103.192184</td> <td align="right">4.4</td> <td align="right">1.5</td> <td align="right">6.0</td> <td align="right">4.0</td> </tr> <tr class="odd"> <td align="right">146.188928</td> <td align="right">3.3</td> <td align="right">2.0</td> <td align="right">5.6</td> <td align="right">3.1</td> </tr> <tr class="even"> <td align="right">146.188928</td> <td align="right">2.8</td> <td align="right">2.3</td> <td align="right">4.5</td> <td align="right">2.9</td> </tr> <tr class="odd"> <td align="right">223.583066</td> <td align="right">1.4</td> <td align="right">1.2</td> <td align="right">4.1</td> <td align="right">1.8</td> </tr> <tr class="even"> <td align="right">223.583066</td> <td align="right">1.8</td> <td align="right">1.9</td> <td align="right">3.9</td> <td align="right">2.6</td> </tr> <tr class="odd"> <td align="right">0.000000</td> <td align="right">93.4</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="even"> <td align="right">0.000000</td> <td align="right">103.2</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="odd"> <td align="right">1.228478</td> <td align="right">89.2</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">1.3</td> </tr> <tr class="even"> <td align="right">1.228478</td> <td align="right">86.6</td> <td align="right">NA</td> <td align="right">NA</td> <td align="right">NA</td> </tr> <tr class="odd"> <td align="right">3.685435</td> <td align="right">78.2</td> <td align="right">2.6</td> <td align="right">1.0</td> <td align="right">3.1</td> </tr> <tr class="even"> <td align="right">3.685435</td> <td align="right">78.1</td> <td align="right">2.4</td> <td align="right">2.6</td> <td align="right">2.3</td> </tr> <tr class="odd"> <td align="right">8.599349</td> <td align="right">55.6</td> <td align="right">5.5</td> <td align="right">4.5</td> <td align="right">3.4</td> </tr> <tr class="even"> <td align="right">8.599349</td> <td align="right">53.0</td> <td align="right">5.6</td> <td align="right">4.6</td> <td align="right">4.3</td> </tr> <tr class="odd"> <td align="right">17.198697</td> <td align="right">33.7</td> <td align="right">7.3</td> <td align="right">7.6</td> <td align="right">7.8</td> </tr> <tr class="even"> <td align="right">17.198697</td> <td align="right">33.2</td> <td align="right">6.5</td> <td align="right">6.7</td> <td align="right">8.7</td> </tr> <tr class="odd"> <td align="right">25.798046</td> <td align="right">20.9</td> <td align="right">5.8</td> <td align="right">8.7</td> <td align="right">7.7</td> </tr> <tr class="even"> <td align="right">25.798046</td> <td align="right">19.9</td> <td align="right">7.7</td> <td align="right">7.6</td> <td align="right">6.5</td> </tr> <tr class="odd"> <td align="right">34.397395</td> <td align="right">18.2</td> <td align="right">7.8</td> <td align="right">8.0</td> <td align="right">6.3</td> </tr> <tr class="even"> <td align="right">34.397395</td> <td align="right">12.7</td> <td align="right">7.3</td> <td align="right">8.6</td> <td align="right">8.7</td> </tr> <tr class="odd"> <td align="right">51.596092</td> <td align="right">7.8</td> <td align="right">7.0</td> <td align="right">7.4</td> <td align="right">5.7</td> </tr> <tr class="even"> <td align="right">51.596092</td> <td align="right">9.0</td> <td align="right">6.3</td> <td align="right">7.2</td> <td align="right">4.2</td> </tr> <tr class="odd"> <td align="right">68.794789</td> <td align="right">11.4</td> <td align="right">4.3</td> <td align="right">10.3</td> <td align="right">3.2</td> </tr> <tr class="even"> <td align="right">68.794789</td> <td align="right">9.0</td> <td align="right">3.8</td> <td align="right">9.4</td> <td align="right">4.2</td> </tr> <tr class="odd"> <td align="right">103.192184</td> <td align="right">3.9</td> <td align="right">2.6</td> <td align="right">6.5</td> <td align="right">3.8</td> </tr> <tr class="even"> <td align="right">103.192184</td> <td align="right">4.4</td> <td align="right">2.8</td> <td align="right">6.9</td> <td align="right">4.0</td> </tr> <tr class="odd"> <td align="right">146.188928</td> <td align="right">2.6</td> <td align="right">1.6</td> <td align="right">4.6</td> <td align="right">4.5</td> </tr> <tr class="even"> <td align="right">146.188928</td> <td align="right">3.4</td> <td align="right">1.1</td> <td align="right">4.5</td> <td align="right">4.5</td> </tr> <tr class="odd"> <td align="right">223.583066</td> <td align="right">2.0</td> <td align="right">1.4</td> <td align="right">4.3</td> <td align="right">3.8</td> </tr> <tr class="even"> <td align="right">223.583066</td> <td align="right">1.7</td> <td align="right">1.3</td> <td align="right">4.2</td> <td align="right">2.3</td> </tr> </tbody> </table> </div> <div class="section level2"> <h2 id="separate-evaluations">Separate evaluations<a class="anchor" aria-label="anchor" href="#separate-evaluations"></a> </h2> <p>As a first step to obtain suitable starting parameters for the NLHM fits, we do separate fits of several variants of the pathway model used previously <span class="citation">(Ranke et al. 2021)</span>, varying the kinetic model for the parent compound. Because the SFORB model often provides faster convergence than the DFOP model, and can sometimes be fitted where the DFOP model results in errors, it is included in the set of parent models tested here.</p> <div class="sourceCode" id="cb4"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="kw">if</span> <span class="op">(</span><span class="op">!</span><span class="fu"><a href="https://rdrr.io/r/base/files2.html" class="external-link">dir.exists</a></span><span class="op">(</span><span class="st">"dmta_dlls"</span><span class="op">)</span><span class="op">)</span> <span class="fu"><a href="https://rdrr.io/r/base/files2.html" class="external-link">dir.create</a></span><span class="op">(</span><span class="st">"dmta_dlls"</span><span class="op">)</span></span> <span><span class="va">m_sfo_path_1</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span></span> <span> DMTA <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"M23"</span>, <span class="st">"M27"</span>, <span class="st">"M31"</span><span class="op">)</span><span class="op">)</span>,</span> <span> M23 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M27 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M31 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"M27"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span> <span> name <span class="op">=</span> <span class="st">"m_sfo_path"</span>, dll_dir <span class="op">=</span> <span class="st">"dmta_dlls"</span>,</span> <span> unload <span class="op">=</span> <span class="cn">TRUE</span>, overwrite <span class="op">=</span> <span class="cn">TRUE</span>,</span> <span> quiet <span class="op">=</span> <span class="cn">TRUE</span></span> <span><span class="op">)</span></span> <span><span class="va">m_fomc_path_1</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span></span> <span> DMTA <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"FOMC"</span>, <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"M23"</span>, <span class="st">"M27"</span>, <span class="st">"M31"</span><span class="op">)</span><span class="op">)</span>,</span> <span> M23 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M27 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M31 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"M27"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span> <span> name <span class="op">=</span> <span class="st">"m_fomc_path"</span>, dll_dir <span class="op">=</span> <span class="st">"dmta_dlls"</span>,</span> <span> unload <span class="op">=</span> <span class="cn">TRUE</span>, overwrite <span class="op">=</span> <span class="cn">TRUE</span>,</span> <span> quiet <span class="op">=</span> <span class="cn">TRUE</span></span> <span><span class="op">)</span></span> <span><span class="va">m_dfop_path_1</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span></span> <span> DMTA <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"DFOP"</span>, <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"M23"</span>, <span class="st">"M27"</span>, <span class="st">"M31"</span><span class="op">)</span><span class="op">)</span>,</span> <span> M23 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M27 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M31 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"M27"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span> <span> name <span class="op">=</span> <span class="st">"m_dfop_path"</span>, dll_dir <span class="op">=</span> <span class="st">"dmta_dlls"</span>,</span> <span> unload <span class="op">=</span> <span class="cn">TRUE</span>, overwrite <span class="op">=</span> <span class="cn">TRUE</span>,</span> <span> quiet <span class="op">=</span> <span class="cn">TRUE</span></span> <span><span class="op">)</span></span> <span><span class="va">m_sforb_path_1</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span></span> <span> DMTA <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFORB"</span>, <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"M23"</span>, <span class="st">"M27"</span>, <span class="st">"M31"</span><span class="op">)</span><span class="op">)</span>,</span> <span> M23 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M27 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M31 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"M27"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span> <span> name <span class="op">=</span> <span class="st">"m_sforb_path"</span>, dll_dir <span class="op">=</span> <span class="st">"dmta_dlls"</span>,</span> <span> unload <span class="op">=</span> <span class="cn">TRUE</span>, overwrite <span class="op">=</span> <span class="cn">TRUE</span>,</span> <span> quiet <span class="op">=</span> <span class="cn">TRUE</span></span> <span><span class="op">)</span></span> <span><span class="va">m_hs_path_1</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinmod</a></span><span class="op">(</span></span> <span> DMTA <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"HS"</span>, <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"M23"</span>, <span class="st">"M27"</span>, <span class="st">"M31"</span><span class="op">)</span><span class="op">)</span>,</span> <span> M23 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M27 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span>,</span> <span> M31 <span class="op">=</span> <span class="fu"><a href="../../reference/mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"M27"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span> <span> name <span class="op">=</span> <span class="st">"m_hs_path"</span>, dll_dir <span class="op">=</span> <span class="st">"dmta_dlls"</span>,</span> <span> unload <span class="op">=</span> <span class="cn">TRUE</span>, overwrite <span class="op">=</span> <span class="cn">TRUE</span>,</span> <span> quiet <span class="op">=</span> <span class="cn">TRUE</span></span> <span><span class="op">)</span></span> <span><span class="va">deg_mods_1</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span></span> <span> sfo_path_1 <span class="op">=</span> <span class="va">m_sfo_path_1</span>,</span> <span> fomc_path_1 <span class="op">=</span> <span class="va">m_fomc_path_1</span>,</span> <span> dfop_path_1 <span class="op">=</span> <span class="va">m_dfop_path_1</span>,</span> <span> sforb_path_1 <span class="op">=</span> <span class="va">m_sforb_path_1</span>,</span> <span> hs_path_1 <span class="op">=</span> <span class="va">m_hs_path_1</span><span class="op">)</span></span> <span></span> <span><span class="va">sep_1_const</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mmkin.html">mmkin</a></span><span class="op">(</span></span> <span> <span class="va">deg_mods_1</span>,</span> <span> <span class="va">dmta_ds</span>,</span> <span> error_model <span class="op">=</span> <span class="st">"const"</span>,</span> <span> quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span> <span></span> <span><span class="fu"><a href="../../reference/status.html">status</a></span><span class="op">(</span><span class="va">sep_1_const</span><span class="op">)</span> <span class="op">|></span> <span class="fu"><a href="https://rdrr.io/pkg/knitr/man/kable.html" class="external-link">kable</a></span><span class="op">(</span><span class="op">)</span></span></code></pre></div> <table class="table"> <thead><tr class="header"> <th align="left"></th> <th align="left">Calke</th> <th align="left">Borstel</th> <th align="left">Flaach</th> <th align="left">BBA 2.2</th> <th align="left">BBA 2.3</th> <th align="left">Elliot</th> </tr></thead> <tbody> <tr class="odd"> <td align="left">sfo_path_1</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="even"> <td align="left">fomc_path_1</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="odd"> <td align="left">dfop_path_1</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">C</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="even"> <td align="left">sforb_path_1</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">C</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="odd"> <td align="left">hs_path_1</td> <td align="left">C</td> <td align="left">C</td> <td align="left">C</td> <td align="left">C</td> <td align="left">C</td> <td align="left">C</td> </tr> </tbody> </table> <p>All separate pathway fits with SFO or FOMC for the parent and constant variance converged (status OK). Most fits with DFOP or SFORB for the parent converged as well. The fits with HS for the parent did not converge with default settings.</p> <div class="sourceCode" id="cb5"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="va">sep_1_tc</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/stats/update.html" class="external-link">update</a></span><span class="op">(</span><span class="va">sep_1_const</span>, error_model <span class="op">=</span> <span class="st">"tc"</span><span class="op">)</span></span> <span><span class="fu"><a href="../../reference/status.html">status</a></span><span class="op">(</span><span class="va">sep_1_tc</span><span class="op">)</span> <span class="op">|></span> <span class="fu"><a href="https://rdrr.io/pkg/knitr/man/kable.html" class="external-link">kable</a></span><span class="op">(</span><span class="op">)</span></span></code></pre></div> <table class="table"> <thead><tr class="header"> <th align="left"></th> <th align="left">Calke</th> <th align="left">Borstel</th> <th align="left">Flaach</th> <th align="left">BBA 2.2</th> <th align="left">BBA 2.3</th> <th align="left">Elliot</th> </tr></thead> <tbody> <tr class="odd"> <td align="left">sfo_path_1</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="even"> <td align="left">fomc_path_1</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">C</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">C</td> </tr> <tr class="odd"> <td align="left">dfop_path_1</td> <td align="left">OK</td> <td align="left">C</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="even"> <td align="left">sforb_path_1</td> <td align="left">OK</td> <td align="left">C</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="odd"> <td align="left">hs_path_1</td> <td align="left">C</td> <td align="left">C</td> <td align="left">C</td> <td align="left">C</td> <td align="left">C</td> <td align="left">OK</td> </tr> </tbody> </table> <p>With the two-component error model, the set of fits with convergence problems is slightly different, with convergence problems appearing for different data sets when applying the DFOP and SFORB model and some additional convergence problems when using the FOMC model for the parent.</p> </div> <div class="section level2"> <h2 id="hierarchichal-model-fits">Hierarchichal model fits<a class="anchor" aria-label="anchor" href="#hierarchichal-model-fits"></a> </h2> <p>The following code fits two sets of the corresponding hierarchical models to the data, one assuming constant variance, and one assuming two-component error.</p> <div class="sourceCode" id="cb6"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="va">saem_1</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/mhmkin.html">mhmkin</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="va">sep_1_const</span>, <span class="va">sep_1_tc</span><span class="op">)</span><span class="op">)</span></span></code></pre></div> <p>The run time for these fits was around two hours on five year old hardware. After a recent hardware upgrade these fits complete in less than twenty minutes.</p> <div class="sourceCode" id="cb7"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="../../reference/status.html">status</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">)</span> <span class="op">|></span> <span class="fu"><a href="https://rdrr.io/pkg/knitr/man/kable.html" class="external-link">kable</a></span><span class="op">(</span><span class="op">)</span></span></code></pre></div> <table class="table"> <thead><tr class="header"> <th align="left"></th> <th align="left">const</th> <th align="left">tc</th> </tr></thead> <tbody> <tr class="odd"> <td align="left">sfo_path_1</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="even"> <td align="left">fomc_path_1</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="odd"> <td align="left">dfop_path_1</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="even"> <td align="left">sforb_path_1</td> <td align="left">OK</td> <td align="left">OK</td> </tr> <tr class="odd"> <td align="left">hs_path_1</td> <td align="left">OK</td> <td align="left">OK</td> </tr> </tbody> </table> <p>According to the <code>status</code> function, all fits terminated successfully.</p> <div class="sourceCode" id="cb8"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/stats/anova.html" class="external-link">anova</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">)</span> <span class="op">|></span> <span class="fu"><a href="https://rdrr.io/pkg/knitr/man/kable.html" class="external-link">kable</a></span><span class="op">(</span>digits <span class="op">=</span> <span class="fl">1</span><span class="op">)</span></span></code></pre></div> <pre><code>Warning in FUN(X[[i]], ...): Could not obtain log likelihood with 'is' method for sforb_path_1 const</code></pre> <table class="table"> <thead><tr class="header"> <th align="left"></th> <th align="right">npar</th> <th align="right">AIC</th> <th align="right">BIC</th> <th align="right">Lik</th> </tr></thead> <tbody> <tr class="odd"> <td align="left">sfo_path_1 const</td> <td align="right">17</td> <td align="right">2291.8</td> <td align="right">2288.3</td> <td align="right">-1128.9</td> </tr> <tr class="even"> <td align="left">sfo_path_1 tc</td> <td align="right">18</td> <td align="right">2276.3</td> <td align="right">2272.5</td> <td align="right">-1120.1</td> </tr> <tr class="odd"> <td align="left">fomc_path_1 const</td> <td align="right">19</td> <td align="right">2099.0</td> <td align="right">2095.0</td> <td align="right">-1030.5</td> </tr> <tr class="even"> <td align="left">fomc_path_1 tc</td> <td align="right">20</td> <td align="right">1939.6</td> <td align="right">1935.5</td> <td align="right">-949.8</td> </tr> <tr class="odd"> <td align="left">dfop_path_1 const</td> <td align="right">21</td> <td align="right">2038.8</td> <td align="right">2034.4</td> <td align="right">-998.4</td> </tr> <tr class="even"> <td align="left">hs_path_1 const</td> <td align="right">21</td> <td align="right">2024.2</td> <td align="right">2019.8</td> <td align="right">-991.1</td> </tr> <tr class="odd"> <td align="left">dfop_path_1 tc</td> <td align="right">22</td> <td align="right">1879.8</td> <td align="right">1875.2</td> <td align="right">-917.9</td> </tr> <tr class="even"> <td align="left">sforb_path_1 tc</td> <td align="right">22</td> <td align="right">1832.9</td> <td align="right">1828.3</td> <td align="right">-894.4</td> </tr> <tr class="odd"> <td align="left">hs_path_1 tc</td> <td align="right">22</td> <td align="right">1831.4</td> <td align="right">1826.8</td> <td align="right">-893.7</td> </tr> </tbody> </table> <p>When the goodness-of-fit of the models is compared, a warning is obtained, indicating that the likelihood of the pathway fit with SFORB for the parent compound and constant variance could not be calculated with importance sampling (method ‘is’). As this is the default method on which all AIC and BIC comparisons are based, this variant is not included in the model comparison table. Comparing the goodness-of-fit of the remaining models, HS model model with two-component error provides the best fit. However, for batch experiments performed with constant conditions such as the experiments evaluated here, there is no reason to assume a discontinuity, so the SFORB model is preferable from a mechanistic viewpoint. In addition, the information criteria AIC and BIC are very similar for HS and SFORB. Therefore, the SFORB model is selected here for further refinements.</p> <div class="section level3"> <h3 id="parameter-identifiability-based-on-the-fisher-information-matrix">Parameter identifiability based on the Fisher Information Matrix<a class="anchor" aria-label="anchor" href="#parameter-identifiability-based-on-the-fisher-information-matrix"></a> </h3> <p>Using the <code>illparms</code> function, ill-defined statistical model parameters such as standard deviations of the degradation parameters in the population and error model parameters can be found.</p> <div class="sourceCode" id="cb10"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="../../reference/illparms.html">illparms</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">)</span> <span class="op">|></span> <span class="fu"><a href="https://rdrr.io/pkg/knitr/man/kable.html" class="external-link">kable</a></span><span class="op">(</span><span class="op">)</span></span></code></pre></div> <table class="table"> <thead><tr class="header"> <th align="left"></th> <th align="left">const</th> <th align="left">tc</th> </tr></thead> <tbody> <tr class="odd"> <td align="left">sfo_path_1</td> <td align="left"></td> <td align="left">sd(DMTA_0)</td> </tr> <tr class="even"> <td align="left">fomc_path_1</td> <td align="left"></td> <td align="left">sd(DMTA_0)</td> </tr> <tr class="odd"> <td align="left">dfop_path_1</td> <td align="left"></td> <td align="left"></td> </tr> <tr class="even"> <td align="left">sforb_path_1</td> <td align="left"></td> <td align="left">sd(log_k_DMTA_bound_free)</td> </tr> <tr class="odd"> <td align="left">hs_path_1</td> <td align="left"></td> <td align="left">sd(log_tb)</td> </tr> </tbody> </table> <p>When using constant variance, no ill-defined variance parameters are identified with the <code>illparms</code> function in any of the degradation models. When using the two-component error model, there is one ill-defined variance parameter in all variants except for the variant using DFOP for the parent compound.</p> <p>For the selected combination of the SFORB pathway model with two-component error, the random effect for the rate constant from reversibly bound DMTA to the free DMTA (<code>k_DMTA_bound_free</code>) is not well-defined. Therefore, the fit is updated without assuming a random effect for this parameter.</p> <div class="sourceCode" id="cb11"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="va">saem_sforb_path_1_tc_reduced</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/stats/update.html" class="external-link">update</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">[[</span><span class="st">"sforb_path_1"</span>, <span class="st">"tc"</span><span class="op">]</span><span class="op">]</span>,</span> <span> no_random_effect <span class="op">=</span> <span class="st">"log_k_DMTA_bound_free"</span><span class="op">)</span></span> <span><span class="fu"><a href="../../reference/illparms.html">illparms</a></span><span class="op">(</span><span class="va">saem_sforb_path_1_tc_reduced</span><span class="op">)</span></span></code></pre></div> <p>As expected, no ill-defined parameters remain. The model comparison below shows that the reduced model is preferable.</p> <div class="sourceCode" id="cb12"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/stats/anova.html" class="external-link">anova</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">[[</span><span class="st">"sforb_path_1"</span>, <span class="st">"tc"</span><span class="op">]</span><span class="op">]</span>, <span class="va">saem_sforb_path_1_tc_reduced</span><span class="op">)</span> <span class="op">|></span> <span class="fu"><a href="https://rdrr.io/pkg/knitr/man/kable.html" class="external-link">kable</a></span><span class="op">(</span>digits <span class="op">=</span> <span class="fl">1</span><span class="op">)</span></span></code></pre></div> <table class="table"> <thead><tr class="header"> <th align="left"></th> <th align="right">npar</th> <th align="right">AIC</th> <th align="right">BIC</th> <th align="right">Lik</th> </tr></thead> <tbody> <tr class="odd"> <td align="left">saem_sforb_path_1_tc_reduced</td> <td align="right">21</td> <td align="right">1830.3</td> <td align="right">1825.9</td> <td align="right">-894.2</td> </tr> <tr class="even"> <td align="left">saem_1[[“sforb_path_1”, “tc”]]</td> <td align="right">22</td> <td align="right">1832.9</td> <td align="right">1828.3</td> <td align="right">-894.4</td> </tr> </tbody> </table> <p>The convergence plot of the refined fit is shown below.</p> <div class="sourceCode" id="cb13"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">saem_sforb_path_1_tc_reduced</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"convergence"</span><span class="op">)</span></span></code></pre></div> <p><img src="2022_dmta_pathway_files/figure-html/saem-sforb-path-1-tc-reduced-convergence-1.png" width="700" style="display: block; margin: auto;"></p> <p>For some parameters, for example for <code>f_DMTA_ilr_1</code> and <code>f_DMTA_ilr_2</code>, i.e. for two of the parameters determining the formation fractions of the parallel formation of the three metabolites, some movement of the parameters is still visible in the second phase of the algorithm. However, the amplitude of this movement is in the range of the amplitude towards the end of the first phase. Therefore, it is likely that an increase in iterations would not improve the parameter estimates very much, and it is proposed that the fit is acceptable. No numeric convergence criterion is implemented in saemix.</p> </div> <div class="section level3"> <h3 id="alternative-check-of-parameter-identifiability">Alternative check of parameter identifiability<a class="anchor" aria-label="anchor" href="#alternative-check-of-parameter-identifiability"></a> </h3> <p>As an alternative check of parameter identifiability <span class="citation">(Duchesne et al. 2021)</span>, multistart runs were performed on the basis of the refined fit shown above.</p> <div class="sourceCode" id="cb14"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="va">saem_sforb_path_1_tc_reduced_multi</span> <span class="op"><-</span> <span class="fu"><a href="../../reference/multistart.html">multistart</a></span><span class="op">(</span><span class="va">saem_sforb_path_1_tc_reduced</span>,</span> <span> n <span class="op">=</span> <span class="fl">32</span>, cores <span class="op">=</span> <span class="fl">10</span><span class="op">)</span></span></code></pre></div> <div class="sourceCode" id="cb15"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">saem_sforb_path_1_tc_reduced_multi</span><span class="op">)</span></span></code></pre></div> <pre><code><multistart> object with 32 fits: E OK 15 17 OK: Fit terminated successfully E: Error</code></pre> <p>Out of the 32 fits that were initiated, only 17 terminated without an error. The reason for this is that the wide variation of starting parameters in combination with the parameter variation that is used in the SAEM algorithm leads to parameter combinations for the degradation model that the numerical integration routine cannot cope with. Because of this variation of initial parameters, some of the model fits take up to two times more time than the original fit.</p> <div class="sourceCode" id="cb17"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/graphics/par.html" class="external-link">par</a></span><span class="op">(</span>mar <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">12.1</span>, <span class="fl">4.1</span>, <span class="fl">2.1</span>, <span class="fl">2.1</span><span class="op">)</span><span class="op">)</span></span> <span><span class="fu"><a href="../../reference/parplot.html">parplot</a></span><span class="op">(</span><span class="va">saem_sforb_path_1_tc_reduced_multi</span>, ylim <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">0.5</span>, <span class="fl">2</span><span class="op">)</span>, las <span class="op">=</span> <span class="fl">2</span><span class="op">)</span></span></code></pre></div> <div class="figure" style="text-align: center"> <img src="2022_dmta_pathway_files/figure-html/unnamed-chunk-2-1.png" alt="Parameter boxplots for the multistart runs that succeeded" width="960"><p class="caption"> Parameter boxplots for the multistart runs that succeeded </p> </div> <p>However, visual analysis of the boxplot of the parameters obtained in the successful fits confirms that the results are sufficiently independent of the starting parameters, and there are no remaining ill-defined parameters.</p> </div> </div> <div class="section level2"> <h2 id="plots-of-selected-fits">Plots of selected fits<a class="anchor" aria-label="anchor" href="#plots-of-selected-fits"></a> </h2> <p>The SFORB pathway fits with full and reduced parameter distribution model are shown below.</p> <div class="sourceCode" id="cb18"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">[[</span><span class="st">"sforb_path_1"</span>, <span class="st">"tc"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></span></code></pre></div> <div class="figure" style="text-align: center"> <img src="2022_dmta_pathway_files/figure-html/unnamed-chunk-3-1.png" alt="SFORB pathway fit with two-component error" width="700"><p class="caption"> SFORB pathway fit with two-component error </p> </div> <div class="sourceCode" id="cb19"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">saem_sforb_path_1_tc_reduced</span><span class="op">)</span></span></code></pre></div> <div class="figure" style="text-align: center"> <img src="2022_dmta_pathway_files/figure-html/unnamed-chunk-4-1.png" alt="SFORB pathway fit with two-component error, reduced parameter model" width="700"><p class="caption"> SFORB pathway fit with two-component error, reduced parameter model </p> </div> <p>Plots of the remaining fits and listings for all successful fits are shown in the Appendix.</p> </div> <div class="section level2"> <h2 id="conclusions">Conclusions<a class="anchor" aria-label="anchor" href="#conclusions"></a> </h2> <p>Pathway fits with SFO, FOMC, DFOP, SFORB and HS models for the parent compound could be successfully performed.</p> </div> <div class="section level2"> <h2 id="acknowledgements">Acknowledgements<a class="anchor" aria-label="anchor" href="#acknowledgements"></a> </h2> <p>The helpful comments by Janina Wöltjen of the German Environment Agency on earlier versions of this document are gratefully acknowledged.</p> </div> <div class="section level2"> <h2 id="references">References<a class="anchor" aria-label="anchor" href="#references"></a> </h2> <div id="refs" class="references csl-bib-body hanging-indent"> <div id="ref-duchesne_2021" class="csl-entry"> Duchesne, Ronan, Anissa Guillemin, Olivier Gandrillon, and Fabien Crauste. 2021. <span>“Practical Identifiability in the Frame of Nonlinear Mixed Effects Models: The Example of the in Vitro Erythropoiesis.”</span> <em>BMC Bioinformatics</em> 22 (478). <a href="https://doi.org/10.1186/s12859-021-04373-4" class="external-link">https://doi.org/10.1186/s12859-021-04373-4</a>. </div> <div id="ref-ranke2021" class="csl-entry"> Ranke, Johannes, Janina Wöltjen, Jana Schmidt, and Emmanuelle Comets. 2021. <span>“Taking Kinetic Evaluations of Degradation Data to the Next Level with Nonlinear Mixed-Effects Models.”</span> <em>Environments</em> 8 (8). <a href="https://doi.org/10.3390/environments8080071" class="external-link">https://doi.org/10.3390/environments8080071</a>. </div> </div> </div> <div class="section level2"> <h2 id="appendix">Appendix<a class="anchor" aria-label="anchor" href="#appendix"></a> </h2> <div class="section level3"> <h3 id="plots-of-hierarchical-fits-not-selected-for-refinement">Plots of hierarchical fits not selected for refinement<a class="anchor" aria-label="anchor" href="#plots-of-hierarchical-fits-not-selected-for-refinement"></a> </h3> <div class="sourceCode" id="cb20"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">[[</span><span class="st">"sfo_path_1"</span>, <span class="st">"tc"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></span></code></pre></div> <div class="figure" style="text-align: center"> <img src="2022_dmta_pathway_files/figure-html/unnamed-chunk-5-1.png" alt="SFO pathway fit with two-component error" width="700"><p class="caption"> SFO pathway fit with two-component error </p> </div> <div class="sourceCode" id="cb21"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">[[</span><span class="st">"fomc_path_1"</span>, <span class="st">"tc"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></span></code></pre></div> <div class="figure" style="text-align: center"> <img src="2022_dmta_pathway_files/figure-html/unnamed-chunk-6-1.png" alt="FOMC pathway fit with two-component error" width="700"><p class="caption"> FOMC pathway fit with two-component error </p> </div> <div class="sourceCode" id="cb22"><pre class="downlit sourceCode r"> <code class="sourceCode R"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">saem_1</span><span class="op">[[</span><span class="st">"sforb_path_1"</span>, <span class="st">"tc"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></span></code></pre></div> <div class="figure" style="text-align: center"> <img src="2022_dmta_pathway_files/figure-html/unnamed-chunk-7-1.png" alt="HS pathway fit with two-component error" width="700"><p class="caption"> HS pathway fit with two-component error </p> </div> </div> <div class="section level3"> <h3 id="hierarchical-model-fit-listings">Hierarchical model fit listings<a class="anchor" aria-label="anchor" href="#hierarchical-model-fit-listings"></a> </h3> <div class="section level4"> <h4 id="fits-with-random-effects-for-all-degradation-parameters">Fits with random effects for all degradation parameters<a class="anchor" aria-label="anchor" href="#fits-with-random-effects-for-all-degradation-parameters"></a> </h4> </div> <div class="section level4"> <h4 id="improved-fit-of-the-sforb-pathway-model-with-two-component-error">Improved fit of the SFORB pathway model with two-component error<a class="anchor" aria-label="anchor" href="#improved-fit-of-the-sforb-pathway-model-with-two-component-error"></a> </h4> </div> </div> <div class="section level3"> <h3 id="session-info">Session info<a class="anchor" aria-label="anchor" href="#session-info"></a> </h3> <pre><code>R version 4.2.2 Patched (2022-11-10 r83330) Platform: x86_64-pc-linux-gnu (64-bit) Running under: Debian GNU/Linux bookworm/sid Matrix products: default BLAS: /usr/lib/x86_64-linux-gnu/openblas-serial/libblas.so.3 LAPACK: /usr/lib/x86_64-linux-gnu/openblas-serial/libopenblas-r0.3.21.so locale: [1] LC_CTYPE=de_DE.UTF-8 LC_NUMERIC=C [3] LC_TIME=de_DE.UTF-8 LC_COLLATE=de_DE.UTF-8 [5] LC_MONETARY=de_DE.UTF-8 LC_MESSAGES=de_DE.UTF-8 [7] LC_PAPER=de_DE.UTF-8 LC_NAME=C [9] LC_ADDRESS=C LC_TELEPHONE=C [11] LC_MEASUREMENT=de_DE.UTF-8 LC_IDENTIFICATION=C attached base packages: [1] parallel stats graphics grDevices utils datasets methods [8] base other attached packages: [1] saemix_3.2 npde_3.3 knitr_1.41 mkin_1.2.2 loaded via a namespace (and not attached): [1] deSolve_1.34 zoo_1.8-11 tidyselect_1.2.0 xfun_0.35 [5] bslib_0.4.2 purrr_1.0.0 lattice_0.20-45 colorspace_2.0-3 [9] vctrs_0.5.1 generics_0.1.3 htmltools_0.5.4 yaml_2.3.6 [13] pkgbuild_1.4.0 utf8_1.2.2 rlang_1.0.6 pkgdown_2.0.7 [17] jquerylib_0.1.4 pillar_1.8.1 glue_1.6.2 DBI_1.1.3 [21] lifecycle_1.0.3 stringr_1.5.0 munsell_0.5.0 gtable_0.3.1 [25] ragg_1.2.4 codetools_0.2-18 memoise_2.0.1 evaluate_0.19 [29] inline_0.3.19 callr_3.7.3 fastmap_1.1.0 ps_1.7.2 [33] lmtest_0.9-40 fansi_1.0.3 highr_0.9 scales_1.2.1 [37] cachem_1.0.6 desc_1.4.2 jsonlite_1.8.4 systemfonts_1.0.4 [41] fs_1.5.2 textshaping_0.3.6 gridExtra_2.3 ggplot2_3.4.0 [45] digest_0.6.31 stringi_1.7.8 processx_3.8.0 dplyr_1.0.10 [49] grid_4.2.2 rprojroot_2.0.3 cli_3.5.0 tools_4.2.2 [53] magrittr_2.0.3 sass_0.4.4 tibble_3.1.8 crayon_1.5.2 [57] pkgconfig_2.0.3 prettyunits_1.1.1 assertthat_0.2.1 rmarkdown_2.19 [61] R6_2.5.1 mclust_6.0.0 nlme_3.1-161 compiler_4.2.2 </code></pre> </div> <div class="section level3"> <h3 id="hardware-info">Hardware info<a class="anchor" aria-label="anchor" href="#hardware-info"></a> </h3> <pre><code>CPU model: AMD Ryzen 9 7950X 16-Core Processor</code></pre> <pre><code>MemTotal: 64940452 kB</code></pre> </div> </div> </div> <div class="col-md-3 hidden-xs hidden-sm" id="pkgdown-sidebar"> <nav id="toc" data-toggle="toc"><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>