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| author | Johannes Ranke <jranke@uni-bremen.de> | 2018-03-01 14:32:46 +0100 |
|---|---|---|
| committer | Johannes Ranke <jranke@uni-bremen.de> | 2018-03-01 14:32:46 +0100 |
| commit | 6653ff2507f45eae909f491a9af3f1eb5358a600 (patch) | |
| tree | 03a43f9cf86cc1d675eba1c6f9c5e31da9c2acdd /docs/articles/FOCUS_Z.html | |
| parent | a767013f407f7495492af6a1ceba4cf2b8aae839 (diff) | |
Static documentation rebuilt using current pkgdown::build_site()
Diffstat (limited to 'docs/articles/FOCUS_Z.html')
| -rw-r--r-- | docs/articles/FOCUS_Z.html | 124 |
1 files changed, 64 insertions, 60 deletions
diff --git a/docs/articles/FOCUS_Z.html b/docs/articles/FOCUS_Z.html index a5cfc616..52a1db77 100644 --- a/docs/articles/FOCUS_Z.html +++ b/docs/articles/FOCUS_Z.html @@ -8,8 +8,11 @@ <title>Example evaluation of FOCUS dataset Z • mkin</title> <!-- jquery --><script src="https://code.jquery.com/jquery-3.1.0.min.js" integrity="sha384-nrOSfDHtoPMzJHjVTdCopGqIqeYETSXhZDFyniQ8ZHcVy08QesyHcnOUpMpqnmWq" crossorigin="anonymous"></script><!-- Bootstrap --><link href="https://maxcdn.bootstrapcdn.com/bootstrap/3.3.7/css/bootstrap.min.css" rel="stylesheet" integrity="sha384-BVYiiSIFeK1dGmJRAkycuHAHRg32OmUcww7on3RYdg4Va+PmSTsz/K68vbdEjh4u" crossorigin="anonymous"> <script src="https://maxcdn.bootstrapcdn.com/bootstrap/3.3.7/js/bootstrap.min.js" integrity="sha384-Tc5IQib027qvyjSMfHjOMaLkfuWVxZxUPnCJA7l2mCWNIpG9mGCD8wGNIcPD7Txa" crossorigin="anonymous"></script><!-- Font Awesome icons --><link href="https://maxcdn.bootstrapcdn.com/font-awesome/4.6.3/css/font-awesome.min.css" rel="stylesheet" integrity="sha384-T8Gy5hrqNKT+hzMclPo118YTQO6cYprQmhrYwIiQ/3axmI1hQomh7Ud2hPOy8SP1" crossorigin="anonymous"> -<!-- pkgdown --><link href="../pkgdown.css" rel="stylesheet"> -<script src="../jquery.sticky-kit.min.js"></script><script src="../pkgdown.js"></script><!-- mathjax --><script src="https://mathjax.rstudio.com/latest/MathJax.js?config=TeX-AMS-MML_HTMLorMML"></script><!--[if lt IE 9]> +<!-- clipboard.js --><script src="https://cdnjs.cloudflare.com/ajax/libs/clipboard.js/1.7.1/clipboard.min.js" integrity="sha384-cV+rhyOuRHc9Ub/91rihWcGmMmCXDeksTtCihMupQHSsi8GIIRDG0ThDc3HGQFJ3" crossorigin="anonymous"></script><!-- pkgdown --><link href="../pkgdown.css" rel="stylesheet"> +<script src="../jquery.sticky-kit.min.js"></script><script src="../pkgdown.js"></script><meta property="og:title" content="Example evaluation of FOCUS dataset Z"> +<meta property="og:description" content=""> +<meta name="twitter:card" content="summary"> +<!-- mathjax --><script src="https://mathjax.rstudio.com/latest/MathJax.js?config=TeX-AMS-MML_HTMLorMML"></script><!--[if lt IE 9]> <script src="https://oss.maxcdn.com/html5shiv/3.7.3/html5shiv.min.js"></script> <script src="https://oss.maxcdn.com/respond/1.4.2/respond.min.js"></script> <![endif]--> @@ -77,7 +80,7 @@ <h1>Example evaluation of FOCUS dataset Z</h1> <h4 class="author">Johannes Ranke</h4> - <h4 class="date">2018-01-16</h4> + <h4 class="date">2018-03-01</h4> </div> @@ -90,64 +93,64 @@ <p>The following code defines the example dataset from Appendix 7 to the FOCUS kinetics report <span class="citation">(FOCUS Work Group on Degradation Kinetics 2014, 354)</span>.</p> <div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">library</span>(mkin, <span class="dt">quietly =</span> <span class="ot">TRUE</span>) LOD =<span class="st"> </span><span class="fl">0.5</span> -FOCUS_2006_Z =<span class="st"> </span><span class="kw">data.frame</span>( +FOCUS_<span class="dv">2006</span>_Z =<span class="st"> </span><span class="kw">data.frame</span>( <span class="dt">t =</span> <span class="kw">c</span>(<span class="dv">0</span>, <span class="fl">0.04</span>, <span class="fl">0.125</span>, <span class="fl">0.29</span>, <span class="fl">0.54</span>, <span class="dv">1</span>, <span class="dv">2</span>, <span class="dv">3</span>, <span class="dv">4</span>, <span class="dv">7</span>, <span class="dv">10</span>, <span class="dv">14</span>, <span class="dv">21</span>, <span class="dv">42</span>, <span class="dv">61</span>, <span class="dv">96</span>, <span class="dv">124</span>), <span class="dt">Z0 =</span> <span class="kw">c</span>(<span class="dv">100</span>, <span class="fl">81.7</span>, <span class="fl">70.4</span>, <span class="fl">51.1</span>, <span class="fl">41.2</span>, <span class="fl">6.6</span>, <span class="fl">4.6</span>, <span class="fl">3.9</span>, <span class="fl">4.6</span>, <span class="fl">4.3</span>, <span class="fl">6.8</span>, <span class="fl">2.9</span>, <span class="fl">3.5</span>, <span class="fl">5.3</span>, <span class="fl">4.4</span>, <span class="fl">1.2</span>, <span class="fl">0.7</span>), <span class="dt">Z1 =</span> <span class="kw">c</span>(<span class="dv">0</span>, <span class="fl">18.3</span>, <span class="fl">29.6</span>, <span class="fl">46.3</span>, <span class="fl">55.1</span>, <span class="fl">65.7</span>, <span class="fl">39.1</span>, <span class="dv">36</span>, <span class="fl">15.3</span>, <span class="fl">5.6</span>, <span class="fl">1.1</span>, - <span class="fl">1.6</span>, <span class="fl">0.6</span>, <span class="fl">0.5</span> *<span class="st"> </span>LOD, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="ot">NA</span>), - <span class="dt">Z2 =</span> <span class="kw">c</span>(<span class="dv">0</span>, <span class="ot">NA</span>, <span class="fl">0.5</span> *<span class="st"> </span>LOD, <span class="fl">2.6</span>, <span class="fl">3.8</span>, <span class="fl">15.3</span>, <span class="fl">37.2</span>, <span class="fl">31.7</span>, <span class="fl">35.6</span>, <span class="fl">14.5</span>, - <span class="fl">0.8</span>, <span class="fl">2.1</span>, <span class="fl">1.9</span>, <span class="fl">0.5</span> *<span class="st"> </span>LOD, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="ot">NA</span>), - <span class="dt">Z3 =</span> <span class="kw">c</span>(<span class="dv">0</span>, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="fl">0.5</span> *<span class="st"> </span>LOD, <span class="fl">9.2</span>, <span class="fl">13.1</span>, <span class="fl">22.3</span>, <span class="fl">28.4</span>, <span class="fl">32.5</span>, + <span class="fl">1.6</span>, <span class="fl">0.6</span>, <span class="fl">0.5</span> <span class="op">*</span><span class="st"> </span>LOD, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="ot">NA</span>), + <span class="dt">Z2 =</span> <span class="kw">c</span>(<span class="dv">0</span>, <span class="ot">NA</span>, <span class="fl">0.5</span> <span class="op">*</span><span class="st"> </span>LOD, <span class="fl">2.6</span>, <span class="fl">3.8</span>, <span class="fl">15.3</span>, <span class="fl">37.2</span>, <span class="fl">31.7</span>, <span class="fl">35.6</span>, <span class="fl">14.5</span>, + <span class="fl">0.8</span>, <span class="fl">2.1</span>, <span class="fl">1.9</span>, <span class="fl">0.5</span> <span class="op">*</span><span class="st"> </span>LOD, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="ot">NA</span>), + <span class="dt">Z3 =</span> <span class="kw">c</span>(<span class="dv">0</span>, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="ot">NA</span>, <span class="fl">0.5</span> <span class="op">*</span><span class="st"> </span>LOD, <span class="fl">9.2</span>, <span class="fl">13.1</span>, <span class="fl">22.3</span>, <span class="fl">28.4</span>, <span class="fl">32.5</span>, <span class="fl">25.2</span>, <span class="fl">17.2</span>, <span class="fl">4.8</span>, <span class="fl">4.5</span>, <span class="fl">2.8</span>, <span class="fl">4.4</span>)) -FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../reference/mkin_wide_to_long.html">mkin_wide_to_long</a></span>(FOCUS_2006_Z)</code></pre></div> +FOCUS_<span class="dv">2006</span>_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../reference/mkin_wide_to_long.html">mkin_wide_to_long</a></span>(FOCUS_<span class="dv">2006</span>_Z)</code></pre></div> </div> <div id="parent-and-one-metabolite" class="section level1"> <h1 class="hasAnchor"> <a href="#parent-and-one-metabolite" class="anchor"></a>Parent and one metabolite</h1> <p>The next step is to set up the models used for the kinetic analysis. As the simultaneous fit of parent and the first metabolite is usually straightforward, Step 1 (SFO for parent only) is skipped here. We start with the model 2a, with formation and decline of metabolite Z1 and the pathway from parent directly to sink included (default in mkin).</p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">Z.2a <-<span class="st"> </span><span class="kw"><a href="../reference/mkinmod.html">mkinmod</a></span>(<span class="dt">Z0 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z1"</span>), +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">Z<span class="fl">.2</span>a <-<span class="st"> </span><span class="kw"><a href="../reference/mkinmod.html">mkinmod</a></span>(<span class="dt">Z0 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z1"</span>), <span class="dt">Z1 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>))</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.2a <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.2a, FOCUS_2006_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) -<span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.2a)</code></pre></div> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z<span class="fl">.2</span>a <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z<span class="fl">.2</span>a, FOCUS_<span class="dv">2006</span>_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) +<span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z<span class="fl">.2</span>a)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_1-1.png" width="672"></p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z.2a, <span class="dt">data =</span> <span class="ot">FALSE</span>)$bpar</code></pre></div> -<pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper -## Z0_0 9.7015e+01 3.553135 2.7304e+01 1.6792e-21 91.4014 102.62838 -## k_Z0_sink 6.2135e-10 0.226894 2.7385e-09 5.0000e-01 0.0000 Inf -## k_Z0_Z1 2.2360e+00 0.165073 1.3546e+01 7.3939e-14 1.8374 2.72107 -## k_Z1_sink 4.8212e-01 0.065854 7.3212e+00 3.5520e-08 0.4006 0.58024</code></pre> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z<span class="fl">.2</span>a, <span class="dt">data =</span> <span class="ot">FALSE</span>)<span class="op">$</span>bpar</code></pre></div> +<pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper +## Z0_0 9.7015e+01 3.553140 2.7304e+01 1.6793e-21 NA NA +## k_Z0_sink 1.2790e-11 0.226895 5.6368e-11 5.0000e-01 NA NA +## k_Z0_Z1 2.2360e+00 0.165073 1.3546e+01 7.3938e-14 NA NA +## k_Z1_sink 4.8212e-01 0.065854 7.3212e+00 3.5520e-08 NA NA</code></pre> <p>As obvious from the parameter summary (the component of the summary), the kinetic rate constant from parent compound Z to sink is very small and the t-test for this parameter suggests that it is not significantly different from zero. This suggests, in agreement with the analysis in the FOCUS kinetics report, to simplify the model by removing the pathway to sink.</p> <p>A similar result can be obtained when formation fractions are used in the model formulation:</p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">Z.2a.ff <-<span class="st"> </span><span class="kw"><a href="../reference/mkinmod.html">mkinmod</a></span>(<span class="dt">Z0 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z1"</span>), +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">Z<span class="fl">.2</span>a.ff <-<span class="st"> </span><span class="kw"><a href="../reference/mkinmod.html">mkinmod</a></span>(<span class="dt">Z0 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z1"</span>), <span class="dt">Z1 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>), <span class="dt">use_of_ff =</span> <span class="st">"max"</span>)</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.2a.ff <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.2a.ff, FOCUS_2006_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) -<span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.2a.ff)</code></pre></div> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z<span class="fl">.2</span>a.ff <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z<span class="fl">.2</span>a.ff, FOCUS_<span class="dv">2006</span>_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) +<span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z<span class="fl">.2</span>a.ff)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_2-1.png" width="672"></p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z.2a.ff, <span class="dt">data =</span> <span class="ot">FALSE</span>)$bpar</code></pre></div> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z<span class="fl">.2</span>a.ff, <span class="dt">data =</span> <span class="ot">FALSE</span>)<span class="op">$</span>bpar</code></pre></div> <pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper -## Z0_0 97.01488 3.553146 27.3039 1.6793e-21 NA NA -## k_Z0 2.23601 0.216847 10.3114 3.6617e-11 NA NA +## Z0_0 97.01488 3.553145 27.3039 1.6793e-21 NA NA +## k_Z0 2.23601 0.216849 10.3114 3.6623e-11 NA NA ## k_Z1 0.48212 0.065854 7.3211 3.5520e-08 NA NA -## f_Z0_to_Z1 1.00000 0.101473 9.8548 9.7071e-11 NA NA</code></pre> +## f_Z0_to_Z1 1.00000 0.101473 9.8548 9.7068e-11 NA NA</code></pre> <p>Here, the ilr transformed formation fraction fitted in the model takes a very large value, and the backtransformed formation fraction from parent Z to Z1 is practically unity. Here, the covariance matrix used for the calculation of confidence intervals is not returned as the model is overparameterised.</p> <p>A simplified model is obtained by removing the pathway to the sink. </p> <p>In the following, we use the parameterisation with formation fractions in order to be able to compare with the results in the FOCUS guidance, and as it makes it easier to use parameters obtained in a previous fit when adding a further metabolite.</p> <div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">Z<span class="fl">.3</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinmod.html">mkinmod</a></span>(<span class="dt">Z0 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z1"</span>, <span class="dt">sink =</span> <span class="ot">FALSE</span>), <span class="dt">Z1 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>), <span class="dt">use_of_ff =</span> <span class="st">"max"</span>)</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z<span class="fl">.3</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z<span class="fl">.3</span>, FOCUS_2006_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z<span class="fl">.3</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z<span class="fl">.3</span>, FOCUS_<span class="dv">2006</span>_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) <span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z<span class="fl">.3</span>)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_3-1.png" width="672"></p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z<span class="fl">.3</span>, <span class="dt">data =</span> <span class="ot">FALSE</span>)$bpar</code></pre></div> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z<span class="fl">.3</span>, <span class="dt">data =</span> <span class="ot">FALSE</span>)<span class="op">$</span>bpar</code></pre></div> <pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper -## Z0_0 97.01488 2.681771 36.176 2.3636e-25 91.52152 102.508 -## k_Z0 2.23601 0.146862 15.225 2.2470e-15 1.95453 2.558 +## Z0_0 97.01488 2.681772 36.176 2.3636e-25 91.52152 102.508 +## k_Z0 2.23601 0.146861 15.225 2.2464e-15 1.95453 2.558 ## k_Z1 0.48212 0.042687 11.294 3.0686e-12 0.40216 0.578</code></pre> <p>As there is only one transformation product for Z0 and no pathway to sink, the formation fraction is internally fixed to unity.</p> </div> @@ -159,7 +162,7 @@ FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../ref <span class="dt">Z1 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z2"</span>, <span class="dt">sink =</span> <span class="ot">FALSE</span>), <span class="dt">Z2 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>), <span class="dt">use_of_ff =</span> <span class="st">"max"</span>)</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z<span class="fl">.5</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z<span class="fl">.5</span>, FOCUS_2006_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z<span class="fl">.5</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z<span class="fl">.5</span>, FOCUS_<span class="dv">2006</span>_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) <span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z<span class="fl">.5</span>)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_5-1.png" width="672"></p> <p>Finally, metabolite Z3 is added to the model. We use the optimised differential equation parameter values from the previous fit in order to accelerate the optimization.</p> @@ -169,25 +172,25 @@ FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../ref <span class="dt">Z3 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>), <span class="dt">use_of_ff =</span> <span class="st">"max"</span>)</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.FOCUS <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.FOCUS, FOCUS_2006_Z_mkin, - <span class="dt">parms.ini =</span> m.Z<span class="fl">.5</span>$bparms.ode, +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.FOCUS <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.FOCUS, FOCUS_<span class="dv">2006</span>_Z_mkin, + <span class="dt">parms.ini =</span> m.Z<span class="fl">.5</span><span class="op">$</span>bparms.ode, <span class="dt">quiet =</span> <span class="ot">TRUE</span>)</code></pre></div> <pre><code>## Warning in mkinfit(Z.FOCUS, FOCUS_2006_Z_mkin, parms.ini = m.Z.5$bparms.ode, : Optimisation by method Port did not converge. ## Convergence code is 1</code></pre> <div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.FOCUS)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_6-1.png" width="672"></p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z.FOCUS, <span class="dt">data =</span> <span class="ot">FALSE</span>)$bpar</code></pre></div> -<pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper -## Z0_0 96.84024 2.058814 47.0369 5.5723e-44 92.706852 100.973637 -## k_Z0 2.21540 0.118128 18.7543 7.7369e-25 1.990504 2.465708 -## k_Z1 0.47836 0.029294 16.3298 3.3443e-22 0.423035 0.540918 -## k_Z2 0.45166 0.044186 10.2218 3.0364e-14 0.371065 0.549767 -## k_Z3 0.05869 0.014290 4.1072 7.2560e-05 0.035983 0.095725 -## f_Z2_to_Z3 0.47147 0.057027 8.2676 2.7790e-11 0.360295 0.585556</code></pre> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z.FOCUS, <span class="dt">data =</span> <span class="ot">FALSE</span>)<span class="op">$</span>bpar</code></pre></div> +<pre><code>## Estimate se_notrans t value Pr(>t) Lower Upper +## Z0_0 96.837112 2.058861 47.0343 5.5877e-44 92.703779 100.970445 +## k_Z0 2.215368 0.118098 18.7587 7.6563e-25 1.990525 2.465609 +## k_Z1 0.478302 0.029289 16.3302 3.3408e-22 0.422977 0.540864 +## k_Z2 0.451617 0.044214 10.2144 3.1133e-14 0.371034 0.549702 +## k_Z3 0.058693 0.014296 4.1056 7.2924e-05 0.035994 0.095705 +## f_Z2_to_Z3 0.471516 0.057057 8.2639 2.8156e-11 0.360381 0.585548</code></pre> <div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw"><a href="../reference/endpoints.html">endpoints</a></span>(m.Z.FOCUS)</code></pre></div> <pre><code>## $ff ## Z2_Z3 Z2_sink -## 0.47147 0.52853 +## 0.47152 0.52848 ## ## $SFORB ## logical(0) @@ -195,9 +198,9 @@ FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../ref ## $distimes ## DT50 DT90 ## Z0 0.31288 1.0394 -## Z1 1.44901 4.8135 -## Z2 1.53466 5.0980 -## Z3 11.81037 39.2332</code></pre> +## Z1 1.44918 4.8141 +## Z2 1.53481 5.0985 +## Z3 11.80973 39.2311</code></pre> <p>This fit corresponds to the final result chosen in Appendix 7 of the FOCUS report. Confidence intervals returned by mkin are based on internally transformed parameters, however.</p> </div> <div id="using-the-sforb-model" class="section level1"> @@ -210,17 +213,17 @@ FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../ref <span class="dt">Z2 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z3"</span>), <span class="dt">Z3 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFORB"</span>))</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.1</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.1</span>, FOCUS_2006_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.1</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.1</span>, FOCUS_<span class="dv">2006</span>_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) <span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.mkin<span class="fl">.1</span>)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_7-1.png" width="672"></p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z.mkin<span class="fl">.1</span>, <span class="dt">data =</span> <span class="ot">FALSE</span>)$cov.unscaled</code></pre></div> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw">summary</span>(m.Z.mkin<span class="fl">.1</span>, <span class="dt">data =</span> <span class="ot">FALSE</span>)<span class="op">$</span>cov.unscaled</code></pre></div> <pre><code>## NULL</code></pre> <p>Therefore, a further stepwise model building is performed starting from the stage of parent and two metabolites, starting from the assumption that the model fit for the parent compound can be improved by using the SFORB model.</p> <div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">Z.mkin<span class="fl">.3</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinmod.html">mkinmod</a></span>(<span class="dt">Z0 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFORB"</span>, <span class="st">"Z1"</span>, <span class="dt">sink =</span> <span class="ot">FALSE</span>), <span class="dt">Z1 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z2"</span>, <span class="dt">sink =</span> <span class="ot">FALSE</span>), <span class="dt">Z2 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>))</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.3</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.3</span>, FOCUS_2006_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.3</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.3</span>, FOCUS_<span class="dv">2006</span>_Z_mkin, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) <span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.mkin<span class="fl">.3</span>)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_9-1.png" width="672"></p> <p>This results in a much better representation of the behaviour of the parent compound Z0.</p> @@ -230,8 +233,8 @@ FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../ref <span class="dt">Z2 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z3"</span>), <span class="dt">Z3 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>))</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.4</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.4</span>, FOCUS_2006_Z_mkin, - <span class="dt">parms.ini =</span> m.Z.mkin<span class="fl">.3</span>$bparms.ode, +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.4</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.4</span>, FOCUS_<span class="dv">2006</span>_Z_mkin, + <span class="dt">parms.ini =</span> m.Z.mkin<span class="fl">.3</span><span class="op">$</span>bparms.ode, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) <span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.mkin<span class="fl">.4</span>)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_10-1.png" width="672"></p> @@ -241,36 +244,36 @@ FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../ref <span class="dt">Z2 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFO"</span>, <span class="st">"Z3"</span>), <span class="dt">Z3 =</span> <span class="kw"><a href="../reference/mkinsub.html">mkinsub</a></span>(<span class="st">"SFORB"</span>))</code></pre></div> <pre><code>## Successfully compiled differential equation model from auto-generated C code.</code></pre> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.5</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.5</span>, FOCUS_2006_Z_mkin, - <span class="dt">parms.ini =</span> m.Z.mkin<span class="fl">.4</span>$bparms.ode[<span class="dv">1</span>:<span class="dv">4</span>], +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.5</span> <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.5</span>, FOCUS_<span class="dv">2006</span>_Z_mkin, + <span class="dt">parms.ini =</span> m.Z.mkin<span class="fl">.4</span><span class="op">$</span>bparms.ode[<span class="dv">1</span><span class="op">:</span><span class="dv">4</span>], <span class="dt">quiet =</span> <span class="ot">TRUE</span>) <span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.mkin<span class="fl">.5</span>)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11-1.png" width="672"></p> <p>The summary view of the backtransformed parameters shows that we get no confidence intervals due to overparameterisation. As the optimized is excessively small, it seems reasonable to fix it to zero.</p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin.5a <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.5</span>, FOCUS_2006_Z_mkin, - <span class="dt">parms.ini =</span> <span class="kw">c</span>(m.Z.mkin<span class="fl">.5</span>$bparms.ode[<span class="dv">1</span>:<span class="dv">7</span>], +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r">m.Z.mkin<span class="fl">.5</span>a <-<span class="st"> </span><span class="kw"><a href="../reference/mkinfit.html">mkinfit</a></span>(Z.mkin<span class="fl">.5</span>, FOCUS_<span class="dv">2006</span>_Z_mkin, + <span class="dt">parms.ini =</span> <span class="kw">c</span>(m.Z.mkin<span class="fl">.5</span><span class="op">$</span>bparms.ode[<span class="dv">1</span><span class="op">:</span><span class="dv">7</span>], <span class="dt">k_Z3_bound_free =</span> <span class="dv">0</span>), <span class="dt">fixed_parms =</span> <span class="st">"k_Z3_bound_free"</span>, <span class="dt">quiet =</span> <span class="ot">TRUE</span>) -<span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.mkin.5a)</code></pre></div> +<span class="kw"><a href="../reference/plot.mkinfit.html">plot_sep</a></span>(m.Z.mkin<span class="fl">.5</span>a)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11a-1.png" width="672"></p> <p>As expected, the residual plots for Z0 and Z3 are more random than in the case of the all SFO model for which they were shown above. In conclusion, the model is proposed as the best-fit model for the dataset from Appendix 7 of the FOCUS report.</p> <p>A graphical representation of the confidence intervals can finally be obtained.</p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw"><a href="../reference/mkinparplot.html">mkinparplot</a></span>(m.Z.mkin.5a)</code></pre></div> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw"><a href="../reference/mkinparplot.html">mkinparplot</a></span>(m.Z.mkin<span class="fl">.5</span>a)</code></pre></div> <p><img src="FOCUS_Z_files/figure-html/FOCUS_2006_Z_fits_11b-1.png" width="672"></p> <p>The endpoints obtained with this model are</p> -<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw"><a href="../reference/endpoints.html">endpoints</a></span>(m.Z.mkin.5a)</code></pre></div> +<div class="sourceCode"><pre class="sourceCode r"><code class="sourceCode r"><span class="kw"><a href="../reference/endpoints.html">endpoints</a></span>(m.Z.mkin<span class="fl">.5</span>a)</code></pre></div> <pre><code>## $ff ## Z0_free_Z1 Z1_Z2 Z2_sink Z2_Z3_free Z3_free_sink ## 1.00000 1.00000 0.46344 0.53656 1.00000 ## ## $SFORB ## Z0_b1 Z0_b2 Z3_b1 Z3_b2 -## 2.4471373 0.0075126 0.0800076 0.0000000 +## 2.4471382 0.0075127 0.0800075 0.0000000 ## ## $distimes ## DT50 DT90 DT50_Z0_b1 DT50_Z0_b2 DT50_Z3_b1 DT50_Z3_b2 -## Z0 0.3043 1.1848 0.28325 92.265 NA NA +## Z0 0.3043 1.1848 0.28325 92.264 NA NA ## Z1 1.5148 5.0320 NA NA NA NA ## Z2 1.6414 5.4526 NA NA NA NA ## Z3 NA NA NA NA 8.6635 Inf</code></pre> @@ -291,7 +294,8 @@ FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../ref <div class="col-md-3 hidden-xs hidden-sm" id="sidebar"> <div id="tocnav"> - <h2>Contents</h2> + <h2 class="hasAnchor"> +<a href="#tocnav" class="anchor"></a>Contents</h2> <ul class="nav nav-pills nav-stacked"> <li><a href="#the-data">The data</a></li> <li><a href="#parent-and-one-metabolite">Parent and one metabolite</a></li> @@ -310,7 +314,7 @@ FOCUS_2006_Z_mkin <-<span class="st"> </span><span class="kw"><a href="../ref </div> <div class="pkgdown"> - <p>Site built with <a href="http://hadley.github.io/pkgdown/">pkgdown</a>.</p> + <p>Site built with <a href="http://pkgdown.r-lib.org/">pkgdown</a>.</p> </div> </footer> |