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th.field-name, table.docinfo th.docinfo-name { + font-weight: bold ; + text-align: left ; + white-space: nowrap ; + padding-left: 0 } + +h1 tt.docutils, h2 tt.docutils, h3 tt.docutils, +h4 tt.docutils, h5 tt.docutils, h6 tt.docutils { + font-size: 100% } + +ul.auto-toc { + list-style-type: none } + +</style> +<!-- configuration parameters --> +<meta name="defaultView" content="slideshow" /> +<meta name="controlVis" content="hidden" /> +<!-- style sheet links --> +<script src="ui/small-white/slides.js" type="text/javascript"></script> +<link rel="stylesheet" href="ui/small-white/slides.css" + type="text/css" media="projection" id="slideProj" /> +<link rel="stylesheet" href="ui/small-white/outline.css" + type="text/css" media="screen" id="outlineStyle" /> +<link rel="stylesheet" href="ui/small-white/print.css" + type="text/css" media="print" id="slidePrint" /> +<link rel="stylesheet" href="ui/small-white/opera.css" + type="text/css" media="projection" id="operaFix" /> + +<style type="text/css"> +#currentSlide {display: none;} +</style> +</head> +<body> +<div class="layout"> +<div id="controls"></div> +<div id="currentSlide"></div> +<div id="header"> + +</div> +<div id="footer"> +<h1>In silico methods for toxicity prediction</h1> +<h2>2012-10-04 <em>in silico</em> toxicology gmbh</h2> +</div> +</div> +<div class="presentation"> +<div class="slide" id="slide0"> +<h1 class="title">In silico methods for toxicity prediction</h1> +<table class="docinfo" frame="void" rules="none"> +<col class="docinfo-name" /> +<col class="docinfo-content" /> +<tbody valign="top"> +<tr><th class="docinfo-name">Author:</th> +<td>Christoph Helma</td></tr> +<tr class="field"><th class="docinfo-name">Affiliation:</th><td class="field-body">in silico toxicology gmbh</td> +</tr> +<tr><th class="docinfo-name">Date:</th> +<td>2012-10-04</td></tr> +</tbody> +</table> + +</div> +<div class="slide" id="outline"> +<h1>Outline</h1> +<ul class="incremental simple"> +<li>In silico toxicology methods</li> +<li>Lazar framework</li> +<li>Products and services</li> +</ul> +</div> +<div class="slide" id="in-silico-methods"> +<h1>In silico methods</h1> +<ul class="incremental simple"> +<li>Systems biology/molecular modeling</li> +<li>Expert systems</li> +<li>Data driven techniques</li> +</ul> +</div> +<div class="slide" id="systems-biology-molecular-modeling"> +<h1>Systems biology/molecular modeling</h1> +<p>Model individual events (e.g. receptor interactions, (de)toxification) of the <em>adverse outcome pathway</em></p> +<ul class="incremental small green simple"> +<li>Mechanistic interpretation</li> +</ul> +<ul class="incremental small red simple"> +<li>Calculations/simulations may be very time consuming</li> +<li>May require a lot of experimental data for parameterization</li> +<li>Impossible to model mechanisms of complex toxicological endpoints</li> +</ul> +<p>Examples: VirtualToxLab/Biograf</p> +</div> +<div class="slide" id="expert-systems"> +<h1>Expert systems</h1> +<p>Formalize expert knowledge about chemicals and toxicity mechanisms and create a software program</p> +<ul class="incremental small green simple"> +<li>Mechanistic interpretation</li> +</ul> +<ul class="incremental small red simple"> +<li>Model creation very time consuming</li> +<li>Many toxicity mechanisms are poorly understood or even unknown</li> +<li>Error prone and hard to validate (strong tendency towards overfitting)</li> +</ul> +<p>Examples: Derek/Lhasa</p> +</div> +<div class="slide" id="data-driven"> +<h1>Data driven</h1> +<p>Use all existing data for a particular endpoint and apply machine learning/QSAR algorithms in order to create a prediction model</p> +<ul class="incremental small green simple"> +<li>Comparably fast</li> +<li>Applicable for every endpoint with sufficient experimental data</li> +<li>Sound validation possible</li> +</ul> +<ul class="incremental small red simple"> +<li>Applicability domain/model quality depends on experimental data</li> +<li>Mechanistic relevance has to be extracted from models/descriptors/predictions</li> +</ul> +<p>Examples: Classical QSARs, Topkat, Multicase, lazar</p> +</div> +<div class="slide" id="lazy-structure-activity-relationships-lazar"> +<h1>Lazy-Structure-Activity Relationships (lazar)</h1> +<p>Automated read across predictions</p> +<ul class="incremental small simple"> +<li>Find <em>similar</em> compounds (=neighbors) with measured activities</li> +<li>Create a local (Q)SAR model with neighbors as training compounds</li> +<li>Make a prediction with this model</li> +</ul> +<p class="incremental">Lazar estimates the confidence (<em>applicability domain</em>) for each prediction</p> +</div> +<div class="slide" id="chemical-similarity"> +<h1>Chemical Similarity</h1> +<p>Can be based on</p> +<ul class="incremental simple"> +<li>Chemical structures</li> +<li>Chemical properties</li> +<li>Biological properties</li> +<li>...</li> +</ul> +<p class="incremental">Lazar uses <em>activity specific similarities</em></p> +</div> +<div class="slide" id="activity-specific-similarities"> +<h1>Activity specific similarities</h1> +<p>Consider only <em>relevant</em> (i.e. statistically significant) substructures, properties, ... for similarity calculations</p> +<p>Algorithms for finding relevant substructures (by A. Maunz):</p> +<ul class="simple"> +<li>Backbone refinement classes (BBRC)</li> +<li>Latent structure mining (LAST)</li> +</ul> +</div> +<div class="slide" id="http-lazar-in-silico-ch"> +<h1><a class="reference external" href="http://lazar.in-silico.ch">http://lazar.in-silico.ch</a></h1> +<img alt="lazar-input.png" class="align-center" src="lazar-input.png" style="height: 13em;" /> +</div> +<div class="slide" id="id1"> +<h1><a class="reference external" href="http://lazar.in-silico.ch">http://lazar.in-silico.ch</a></h1> +<img alt="lazar-output1.png" class="align-center" src="lazar-output1.png" style="height: 13em;" /> +</div> +<div class="slide" id="id2"> +<h1><a class="reference external" href="http://lazar.in-silico.ch">http://lazar.in-silico.ch</a></h1> +<img alt="lazar-output2.png" class="align-center" src="lazar-output2.png" style="height: 13em;" /> +</div> +<div class="slide" id="id3"> +<h1><a class="reference external" href="http://lazar.in-silico.ch">http://lazar.in-silico.ch</a></h1> +<img alt="lazar-output3.png" class="align-center" src="lazar-output3.png" style="height: 13em;" /> +</div> +<div class="slide" id="lazar-limitations"> +<h1>Lazar limitations</h1> +<ul class="incremental simple"> +<li>Model quality depends on data quality</li> +<li>Applicability domain depends on learning instances</li> +</ul> +</div> +<div class="slide" id="in-silico-toxicology-gmbh"> +<h1>in silico toxicology gmbh</h1> +<p>Open source software and algorithm development</p> +<ul class="incremental simple"> +<li>Predictive toxicology and QSAR models</li> +<li>Toxicological data mining</li> +<li>Life science webservices and data warehouses</li> +</ul> +</div> +<div class="slide" id="why-open-source"> +<h1>Why open source?</h1> +<ul class="incremental simple"> +<li>Clear and unambiguous documentation of implemented algorithms essential for scientific software (also required by many regulatory guidelines)</li> +<li>Collaboration with partners, projects and external contributors</li> +<li>Establishment of international standards</li> +<li>Security of investment</li> +</ul> +</div> +<div class="slide" id="eu-research-projects-fp6-7"> +<h1>EU Research projects (FP6/7)</h1> +<table class="small docutils field-list" frame="void" rules="none"> +<col class="field-name" /> +<col class="field-body" /> +<tbody valign="top"> +<tr class="field"><th class="field-name">Sens-it-iv:</th><td class="field-body">Novel testing strategies for in vitro assessment of allergens</td> +</tr> +<tr class="field"><th class="field-name">Scarlet:</th><td class="field-body">Network on in silico methods for carcinogenicity and mutagenicity</td> +</tr> +<tr class="field"><th class="field-name">OpenTox:</th><td class="field-body">Open source framework for predictive toxicology</td> +</tr> +<tr class="field"><th class="field-name">ToxBank:</th><td class="field-body">Integrated data analysis and servicing of alternative testing methods in toxicology</td> +</tr> +<tr class="field"><th class="field-name">ModNanoTox:</th><td class="field-body">Modelling toxicity behaviour of engineered nanoparticles</td> +</tr> +</tbody> +</table> +</div> +<div class="slide" id="free-products-and-services"> +<h1>Free products and services</h1> +<table class="docutils field-list" frame="void" rules="none"> +<col class="field-name" /> +<col class="field-body" /> +<tbody valign="top"> +<tr class="field"><th class="field-name" colspan="2">Lazar application:</th></tr> +<tr class="field"><td> </td><td class="field-body"><a class="reference external" href="http://lazar.in-silico.ch">http://lazar.in-silico.ch</a></td> +</tr> +<tr class="field"><th class="field-name" colspan="2">OpenTox Webservices:</th></tr> +<tr class="field"><td> </td><td class="field-body"><a class="reference external" href="http://webservices.in-silico.ch">http://webservices.in-silico.ch</a></td> +</tr> +<tr class="field"><th class="field-name">Source code:</th><td class="field-body"><a class="reference external" href="https://github.com/opentox">https://github.com/opentox</a></td> +</tr> +</tbody> +</table> +<p>Issue tracker, documentation, ...</p> +</div> +<div class="slide" id="commercial-products-and-services"> +<h1>Commercial products and services</h1> +<ul class="incremental simple"> +<li>Lazar "software as a service" (SaaS): secure access for confidential predictions, batch predictions, ...</li> +<li>Virtual appliances with lazar software for in-house/desktop installation</li> +<li>Installation services</li> +<li>Phone and email support</li> +</ul> +</div> +<div class="slide" id="id4"> +<h1>Commercial products and services</h1> +<ul class="incremental simple"> +<li>Virtual toxicity screening of compounds and libraries</li> +<li>Development of prediction models for new endpoints</li> +<li>Scientific programming, contract research and consulting</li> +</ul> +</div> +<div class="slide" id="contact"> +<h1>Contact</h1> +<table class="docutils field-list" frame="void" rules="none"> +<col class="field-name" /> +<col class="field-body" /> +<tbody valign="top"> +<tr class="field"><th class="field-name">Web:</th><td class="field-body"><a class="reference external" href="http://www.in-silico.ch">http://www.in-silico.ch</a></td> +</tr> +<tr class="field"><th class="field-name">Email:</th><td class="field-body"><a class="reference external" href="mailto:helma@in-silico.ch">helma@in-silico.ch</a></td> +</tr> +</tbody> +</table> +</div> +</div> +</body> +</html> |