2080 lines
76 KiB
HTML
2080 lines
76 KiB
HTML
<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN"
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"http://www.w3.org/TR/REC-html40/loose.dtd">
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<html>
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<meta name="GENERATOR" content="TtH 3.81">
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<style type="text/css"> div.p { margin-top: 7pt;}</style>
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<style type="text/css"><!--
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td div.comp { margin-top: -0.6ex; margin-bottom: -1ex;}
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td div.comb { margin-top: -0.6ex; margin-bottom: -.6ex;}
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td div.hrcomp { line-height: 0.9; margin-top: -0.8ex; margin-bottom: -1ex;}
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td div.norm {line-height:normal;}
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span.roman {font-family: serif; font-style: normal; font-weight: normal;}
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span.overacc2 {position: relative; left: .8em; top: -1.2ex;}
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span.overacc1 {position: relative; left: .6em; top: -1.2ex;} --></style>
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<title> ATACS User's Manual</title>
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<h1 align="center">ATACS User's Manual </h1>
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<div class="p"><!----></div>
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<h3 align="center">Chris J. Myers, Kevin Jones, Scott Little, Nicholas Seegmiller, Robert Thacker, David Walter </h3>
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<div class="p"><!----></div>
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<div class="p"><!----></div>
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<div class="p"><!----></div>
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<div class="p"><!----></div>
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<h2><a name="tth_sEc1">
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1</a> Introduction</h2>
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<div class="p"><!----></div>
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LEMA has been developed for the formal verification of analog and mixed-signal (AMS) circuits. LEMA includes the following tools:
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<div class="p"><!----></div>
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<ul>
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<li> LHPN Editor - a tool to create a model using the
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<em>labeled hybrid Petri net</em> (LHPN) format.<br />
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The LHPN format is described in
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<A HREF="http://www.async.ece.utah.edu/publications">
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David Walter and Scott Little's PhD dissertations
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</A>
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(UofUtah 2007/2008).
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<div class="p"><!----></div>
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</li>
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<li> Verification tool - a tool to perform model checking on a LHPN model. The tool can use DBM, BDD, or SMT to represent the state space.
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These model checkers are described in
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<A HREF="http://www.async.ece.utah.edu/publications">
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David Walter and Scott Little's PhD dissertations
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</A>
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(UofUtah 2007/2008).
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<div class="p"><!----></div>
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</li>
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<li> Learn tool - a tool to learn a LHPN from simulation data.<br />
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This tool is described in
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<A HREF="http://www.async.ece.utah.edu/publications">
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Scott Little's PhD Dissertation
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</A>
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(UofUtah 2008).
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<div class="p"><!----></div>
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</li>
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<li> TSD Graph Editor- a tool to visualize TSD files.
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<div class="p"><!----></div>
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</li>
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</ul>
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<div class="p"><!----></div>
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<h2><a name="tth_sEc2">
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2</a> Project Management</h2>
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<div class="p"><!----></div>
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A project is a collection of models, analysis views, learn
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views, and graphs. As shown below, <tt>iBioSim</tt> displays all project
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files on the left, the open models, views, and graphs on the
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right, and a log of all external commands on the bottom.
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The menu bar is located on the top of the window in the Windows and
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Linux versions. It is located on the top of the screen in the MacOS version.
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<center>
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<img src="screenshots/iBioSim.png" alt="screenshots/iBioSim.png" />
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</center>
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<div class="p"><!----></div>
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<h3><a name="tth_sEc2.1">
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2.1</a> Creating and Opening Projects</h3>
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<div class="p"><!----></div>
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To create a new project, select New → Project from the File
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menu as shown below. You will then be prompted to browse to a desired location
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and to give a name to the project directory. After you do this,
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click the new button and a new project directory will be created.
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To open a project, select Open → Project from the File menu.
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You will then be prompted to browse to a project directory to
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open, and clicking open will open the project. You may also open
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a project by selecting one of your five most recently opened
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projects by selecting the project name shown in the File drop
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down menu shown below.
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<center>
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<img src="screenshots/project.png" alt="screenshots/project.png" />
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</center>
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<div class="p"><!----></div>
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<h3><a name="tth_sEc2.2">
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2.2</a> Creating Models and Graphs</h3>
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<div class="p"><!----></div>
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After you have created or opened a project, you can create a
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new model or graph to add to the project. To create a new
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Genetic Circuit Model (see Section ), select
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New → Genetic Circuit Model from the
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File menu as shown below. You will then be prompted to give a model id. At this
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point, a GCM editor (see Section ) will open in a new
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tab. To create a new SBML model, select New → SBML Model
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from the File menu. You will then be prompted to give a model id.
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At this point, an SBML editor (see Section ) will open
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in a new tab. To create a new TSD graph, select New → TSD Graph
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from the File menu. You will then be prompted to give a name to
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the TSD graph. At this point, a TSD graph editor (see Section )
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will open in a new tab. To create a new probability graph, select
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New → Probability Graph from the File menu. You will then
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be prompted to give a name to the probability graph. At this point, a
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probability graph editor (see Section )
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will open in a new tab. Once a model or graph is created, it can
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be opened again later by right clicking on the object in the
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project window and selecting "Edit", or alternatively
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double-clicking on the object.
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<center>
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<img src="screenshots/newModel.png" alt="screenshots/newModel.png" />
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</center>
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<div class="p"><!----></div>
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<h3><a name="tth_sEc2.3">
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2.3</a> Importing Models</h3>
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<div class="p"><!----></div>
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You can import into the current working project GCMs
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or SBML Models created by other programs or stored in other projects.
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To import a GCM, select Import → Genetic Circuit Model
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from the File menu as shown below. You will then be able to browse to
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find a model to import. After selecting the desired model, click the
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import button
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to bring the GCM into the project. Before bringing the model into the
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project, it will be checked to see if it is a valid GCM file.
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To import an SBML model, the procedure is the same except use the
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Import → SBML Model option. Before bringing the model
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into the project, it will be checked to see if it a valid SBML file.
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The model will also be checked for consistency, and any errors or
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warnings will be reported. These should be corrected before analysis
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of the model is performed.
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<center>
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<img src="screenshots/import.png" alt="screenshots/import.png" />
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</center>
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<div class="p"><!----></div>
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<h3><a name="tth_sEc2.4">
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2.4</a> Editing Project Objects</h3>
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<div class="p"><!----></div>
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All project objects can be modified by highlighting the object
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and using a right mouse click to open a menu of options as shown
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below. Using this menu, every type of object can be copied, renamed, or
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deleted. For a GCM, the "View/Edit" option opens the
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model in a GCM editor (see Section ). For an SBML model,
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the "View/Edit" option opens the model in an SBML editor
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(see Section ). For a TSD graph, the "View/Edit"
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option opens the TSD graph in a TSD graph editor (see Section ).
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For a probability graph, the "View/Edit" option opens
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the probability graph in a probability graph editor
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(see Section ).
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For an analysis view, the "Open Analysis View" option opens the
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analysis view (see Section ). For a learn view, the
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"Open Learn View" option opens the learn view (see Section ).
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<div class="p"><!----></div>
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<center>
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<table>
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<tr><td align="center"><img src="screenshots/modGCM.png" alt="screenshots/modGCM.png" /> </td><td align="center"></td><td align="center"><img src="screenshots/modSBML.png" alt="screenshots/modSBML.png" /> </td></tr>
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<tr><td align="center"></td></tr>
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<tr><td align="center"><img src="screenshots/modAnalysis.png" alt="screenshots/modAnalysis.png" /> </td><td align="center"></td><td align="center"><img src="screenshots/modLearn.png" alt="screenshots/modLearn.png" />
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</td></tr></table>
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</center>
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<div class="p"><!----></div>
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<h3><a name="tth_sEc2.5">
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2.5</a> Viewing Project Objects</h3>
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<div class="p"><!----></div>
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A GCM can also be viewed using
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<A HREF="http://www.graphviz.org/">
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GraphViz's
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</A>
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dotty program by right clicking on the model you want to view and
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selecting the "View Genetic Circuit" option.
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There are two additional ways to view an SBML model. You
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can either select the "View Network" option or the
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"View in Browser" option. The "View Network"
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option converts the model to a GraphViz file and then will open that
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file with GraphViz's dotty program. The "View in Browser" option
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coverts the model to an xhtml file and opens that file with your
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default xhtml browser.
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<div class="p"><!----></div>
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<center>
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<table>
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<tr><td align="center"><img src="screenshots/modGCM.png" alt="screenshots/modGCM.png" /> </td><td align="center"></td><td align="center"><img src="screenshots/modSBML.png" alt="screenshots/modSBML.png" /> </td></tr>
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<tr><td align="center"></td></tr>
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<tr><td align="center"><img src="screenshots/modAnalysis.png" alt="screenshots/modAnalysis.png" /> </td><td align="center"></td><td align="center"><img src="screenshots/modLearn.png" alt="screenshots/modLearn.png" />
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</td></tr></table>
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</center>
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<div class="p"><!----></div>
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<h3><a name="tth_sEc2.6">
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2.6</a> Creating Tool Views</h3>
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<div class="p"><!----></div>
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To perform analysis or learning, right click on a model and
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select "Create Analysis View" (see Section )
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to perform analysis or "Create Learn View" (see Section )
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to perform learning. You will then be prompted to give a name to
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your analysis or learn view. After a name is entered, a tab with
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the newly created view will open. Once a view is created, it can
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be opened again later by right clicking on an analysis directory
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and selecting "Open Analysis/Learn View" or alternatively
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double-clicking on the view.
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<center>
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<table>
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<tr><td align="center"><img src="screenshots/createAnalysis.png" alt="screenshots/createAnalysis.png" /> </td><td align="center"></td><td align="center"><img src="screenshots/createLearn.png" alt="screenshots/createLearn.png" />
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</td></tr></table>
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</center>
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<div class="p"><!----></div>
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When you create an analysis view from a GCM, an SBML model is
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automatically created for simulation and analysis. Within the
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analysis view, you can edit the initial concentrations and
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parameters. However, if you wish to be able to edit the
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structure, you should first create an SBML model using Create
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SBML Model option in the right click menu or the Save as SBML button in
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the GCM Editor (see Section ). You can then open and
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edit this model using an SBML editor (see Section ) and
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create an analysis view from this edited model.
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<div class="p"><!----></div>
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<h2><a name="tth_sEc3">
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3</a> <a name="SBMLEdit">
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</a>SBML Editor</h2>
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<div class="p"><!----></div>
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The SBML editor as shown below allows the user to create or modify an SBML
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model of a biochemical reaction network. An SBML model includes
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compartments (see Section ),
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species (see Section ),
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reactions (see Section ),
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parameters (see Section ),
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function definitions (see Section ),
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unit definitions (see Section ),
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compartment types (see Section ),
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species types (see Section ),
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initial assignments (see Section ),
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rules (see Section ),
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constraints (see Section ), and
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events (see Section ).
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Each of these items can be added, removed, or edited.
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To add a new item, click on the appropriate add button. You
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will then be prompted to provide a unique id and some properties
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for this new item (as described below). After you have filled out
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all of the required fields, click add and the new item will be
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added to the SBML model.
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To remove an item from the model, select that item and click
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the remove button. The item will then be removed from the model.
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However, if you try to remove an item that is being used
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(for example, a species that is used in a reaction), you will first have
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to remove its use.
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To edit an existing item, select that item from the list and
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click the edit button. An editing window will open and you will
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be able to change the properties of that item. When you are done
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editing this item, click save to save the changes to the item.
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After the model is complete, press the Save SBML button to store
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the model. The Save and Check SBML button also saves the model, but
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in this case it also checks the models consistency.
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Note that many checks are done on the fly, so it should be difficult
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to create models with consistency problems. However, if a user does
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not wish to be warned about undeclared units or does not wish to have
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units checked at all can set preferences to turn this off
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(see Section ). The Save and Check SBML button
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though will still present all the unit warnings and errors.
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Finally, the Save As button can also be used to store the
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model, but in this case, a new model ID will be requested and the
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model will be saved using that ID.
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<center>
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<img src="screenshots/SBMLedit.png" alt="screenshots/SBMLedit.png" />
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</center>
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<div class="p"><!----></div>
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<h3><a name="tth_sEc3.1">
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3.1</a> <a name="SBMLMath">
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</a>SBML Math Formulas</h3>
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<div class="p"><!----></div>
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Math formulas appear in many SBML constructs. These formulas are
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expressed as text strings using a simple C-like syntax.
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SBML math formulas can include:
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<ul>
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<li> Variables (compartment, species, parameter IDs, and reaction IDs)
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<div class="p"><!----></div>
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</li>
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<li> Real Numbers
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<div class="p"><!----></div>
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</li>
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<li> Built-in constants: exponentiale, pi, true, and false.
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<div class="p"><!----></div>
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</li>
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<li> Special variable time or t which returns the current simulation time.
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<div class="p"><!----></div>
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</li>
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<li> Mathematical operators including add (+), subtract (-), multiply
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(*), divide (/), and power (x^y) which is equivalent to pow(x,y).
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<div class="p"><!----></div>
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</li>
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<li> A function defined in the list of function definitions.
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<div class="p"><!----></div>
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</li>
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<li> Logical functions: and, or, xor, not.
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<div class="p"><!----></div>
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</li>
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<li> Relational functions: eq, neq, geq, gt, leq, and lt.
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<div class="p"><!----></div>
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</li>
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<li> Unary functions: abs, ceiling, exp, factorial, floor, ln, log,
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sqr, and sqrt.
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<div class="p"><!----></div>
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</li>
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<li> Trigonometric functions: cos, cosh, sin, sinh, tan, tanh, cot,
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coth, csc, csch, sec, sech, arccos, arccosh, arcsin, arcsinh,
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arctan, arctanh, arccot, arccoth, arccsc, arccsch, arcsec, and arcsech.
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<div class="p"><!----></div>
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</li>
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<li> The delay(expr1,expr2) function which returns the value of expr1 at a time
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expr2 time units earlier (not currently supported by analysis).
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<div class="p"><!----></div>
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</li>
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<li> The piecewise(value1, case1, value2, case2, ..., otherwise)
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function returns value1 if case1 is true, value2 if case2 is true,
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etc. If no cases are true, it returns otherwise value.
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<div class="p"><!----></div>
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</li>
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</ul>
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<div class="p"><!----></div>
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<tt>iBioSim</tt>'s simulators also support several random functions which
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are added by default to any SBML file created with its SBML editor.
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The following random functions, therefore, can also be used in SBML
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math formula:
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<ul>
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<li> Continuous random functions: uniform(a,b), normal(m,s), exponential(mu),
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gamma(a,b), lognormal(z,s), chisq(nu), laplace(a), cauchy(a), and
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rayleigh(s).
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<div class="p"><!----></div>
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</li>
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<li> Discrete random functions: poisson(mu), binomial(p,n), and bernoulli(p).
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<div class="p"><!----></div>
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</li>
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</ul>
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<div class="p"><!----></div>
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<h3><a name="tth_sEc3.2">
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3.2</a> <a name="MainElem">
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</a>Main Elements</h3>
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<div class="p"><!----></div>
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This Main Elements tab shown below is used to specify
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compartments (see Section ),
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species (see Section ),
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reactions (see Section ), and
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parameters (see Section ).
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This tab also includes the Model ID which is fixed to be the same as
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the filename as well as the Model Name which can be used to provide an
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arbitrary string description of the model.
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<center>
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<img src="screenshots/mainElem.png" alt="screenshots/mainElem.png" />
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</center>
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<div class="p"><!----></div>
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<h4><a name="tth_sEc3.2.1">
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3.2.1</a> <a name="compartments">
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</a>Compartments</h4>
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<div class="p"><!----></div>
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Compartments are used to specify locations where species are
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found. Every model must include at least one compartment. A new
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model includes a compartment named "default" that
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cannot be removed unless a new compartment is provided.
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A compartment to which species have been assigned also cannot be removed.
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As shown below, a compartment has the following fields:
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<ul>
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<li> ID: a unique ID composed of only alphanumeric characters and
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underscores.
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<div class="p"><!----></div>
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</li>
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<li> Name: an arbitrary string description (optional).
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<div class="p"><!----></div>
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</li>
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<li> Type: selected from the list of compartment types (default=none).
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<div class="p"><!----></div>
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</li>
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<li> Dimensions: number of spatial dimensions (default=3).
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<div class="p"><!----></div>
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</li>
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<li> Outside: the compartment that is outside this compartment
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(default=none).
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<div class="p"><!----></div>
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</li>
|
|
|
|
<li> Constant: Boolean indicating if the size is constant
|
|
(default=true).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Size: initial size of the compartment (default=1.0).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Units: the units for the size (default=none).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<center>
|
|
<img src="screenshots/compartment.png" alt="screenshots/compartment.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.2.2">
|
|
3.2.2</a> <a name="species">
|
|
</a>Species</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Species are the molecules that appear as reactants, products, or modifiers
|
|
in the reactions in the biochemical reaction network.
|
|
As shown below, a species has the following fields:
|
|
|
|
<ul>
|
|
<li> ID: a unique ID composed of only alphanumeric characters and
|
|
underscores.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Name: an arbitrary string description (optional).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Type: selected from the list of species types (default=none).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Compartment: location of the species (default=default).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Boundary Condition: Boolean indicating if the species
|
|
amount/concentration
|
|
cannot be changed by reactions (default=false).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Constant: Boolean indicating if the species amount/concentration
|
|
is constant (default=false).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Initial Amount/Concentration: initial value of the amount or
|
|
concentration of the species. Whether it is an amount or concentration
|
|
can also be selected (default=amount/0.0).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Units: the units for the amount/concentration (default=none).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<center>
|
|
<img src="screenshots/species.png" alt="screenshots/species.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.2.3">
|
|
3.2.3</a> <a name="reactions">
|
|
</a>Reactions</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Reactions are used to create or destroy molecular species in a
|
|
biochemical reaction network. As shown below, a
|
|
reaction is composed of the following:
|
|
|
|
<ul>
|
|
<li> ID: a unique ID composed only of alphanumeric characters and
|
|
underscores.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Name: an arbitrary string description (optional).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Reversible: a Boolean indicating if the reaction is reversible
|
|
(default=false).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Fast: a Boolean indicating if the reaction is fast (default=false).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> List of Reactants: species that are consumed by this reaction.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> List of Products: species that are produced by this reaction.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> List of Modifiers: species that are neither produced or consumed
|
|
by this reaction.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> List of Local Parameters: symbolic values that can be used in
|
|
the kinetic law or stoichiometry math formulas for this reaction.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Kinetic law: an SBML math formula (see Section <a href="#SBMLMath">3.1</a>)
|
|
describing the rate or probability for this reaction.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
When adding a reactant or product, the user must specify a species ID and
|
|
the stoichiometry (i.e., the number of molecules produced or consumed by the
|
|
reaction). The stoichiometry can also be expressed as a stoichiometry math
|
|
formula. Each parameter is composed of an ID, Name, Value, and Units.
|
|
The list of parameters begins with a default forward
|
|
reaction rate (kf) and reverse reaction rate (kr). These names
|
|
and their values should likely be edited. The kinetic law can
|
|
either be automatically generated using the Use Mass Action
|
|
button or manually entered. The
|
|
"Use Mass Action" button creates a rate law using the
|
|
law of mass action. It assumes that the first parameter in the
|
|
list is the forward reaction rate and the second parameter in the
|
|
list is the reverse reaction rate.
|
|
The "Clear" button clears the kinetic law editor.
|
|
The stoichiometry math and kinetic law formulas can only include
|
|
those species that appear as reactants, products, or modifiers.
|
|
|
|
<center>
|
|
<img src="screenshots/reaction.png" alt="screenshots/reaction.png" />
|
|
|
|
<table>
|
|
<tr><td align="center"><img src="screenshots/reactant.png" alt="screenshots/reactant.png" /> </td><td align="center"><img src="screenshots/product.png" alt="screenshots/product.png" />
|
|
</td></tr></table>
|
|
|
|
<img src="screenshots/localParam.png" alt="screenshots/localParam.png" /><br />
|
|
<img src="screenshots/kineticLaw.png" alt="screenshots/kineticLaw.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.2.4">
|
|
3.2.4</a> <a name="parameters">
|
|
</a>Global Parameters</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Global parameters are variables that can
|
|
be used in SBML math formulas (see Section <a href="#SBMLMath">3.1</a>).
|
|
As shown below, a parameter includes the following:
|
|
|
|
<ul>
|
|
<li> ID: a unique ID composed only of alphanumeric characters and
|
|
underscores.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Name: an arbitrary string description (optional).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Value: initial value for the parameter.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Units: the units for the parameter value (default=none).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Constant: Boolean indicating if the parameter value
|
|
is constant (default=true).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<center>
|
|
<img src="screenshots/parameter.png" alt="screenshots/parameter.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc3.3">
|
|
3.3</a> <a name="DefnTypes">
|
|
</a>Definitions/Types</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
The Definitions/Types tab shown below allows users to provide
|
|
function definitions (see Section ),
|
|
unit definitions (see Section ),
|
|
compartment types (see Section ), and
|
|
species types (see Section ).
|
|
|
|
<center>
|
|
<img src="screenshots/DefnTypes.png" alt="screenshots/DefnTypes.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.3.1">
|
|
3.3.1</a> <a name="funcDefn">
|
|
</a>Function Definitions</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Function definitions are used to create user defined functions that
|
|
can then be used in SBML math formulas (see Section <a href="#SBMLMath">3.1</a>).
|
|
As shown below, function definitions include an ID, an optional name field, a
|
|
comma-separated list of arguments, and its definition. The definition
|
|
is an SBML math formula though it is restricted to only use variable
|
|
names which are arguments to the function. While functions can
|
|
call other functions, they cannot be recursive (i.e., call themselves)
|
|
either directly or indirectly (i.e., through a cycle of function calls).
|
|
As mentioned earlier, several random functions supported by
|
|
<tt>iBioSim</tt>'s simulators are added automatically.
|
|
|
|
<center>
|
|
<img src="screenshots/function.png" alt="screenshots/function.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.3.2">
|
|
3.3.2</a> <a name="unitDefn">
|
|
</a>Unit Definitions</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Unit definitions are used to construct user-defined units which are
|
|
derived from the set of base units. As shown below, a
|
|
unit definition includes an ID,
|
|
an optional name, and a list of units that define it. There are
|
|
buttons to add, remove, and edit elements in the list of units.
|
|
Each unit is composed of a kind, exponent, scale, and multiplier. The kind
|
|
is selected from the list of base units in the table below:
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<center>
|
|
<table border="1">
|
|
<tr><td align="center">ampere </td><td align="center">gram </td><td align="center">katal </td><td align="center">metre </td><td align="center">second </td><td align="center">watt </td></tr>
|
|
<tr><td align="center">bacquerel </td><td align="center">gray </td><td align="center">kelvin </td><td align="center">mole </td><td align="center">siemens </td><td align="center">weber </td></tr>
|
|
<tr><td align="center">candela </td><td align="center">henry </td><td align="center">kilogram </td><td align="center">newton </td><td align="center">sievert </td><td align="center"> </td></tr>
|
|
<tr><td align="center">coulomb </td><td align="center">hertz </td><td align="center">litre </td><td align="center">ohm </td><td align="center">steradian </td><td align="center"> </td></tr>
|
|
<tr><td align="center">dimensionless </td><td align="center">item </td><td align="center">lumen </td><td align="center">pascal </td><td align="center">tesla </td><td align="center"> </td></tr>
|
|
<tr><td align="center">farad </td><td align="center">joule </td><td align="center">lux </td><td align="center">radian </td><td align="center">volt </td><td align="center"> </td></tr></table>
|
|
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
The exponent and scale are integers, and the multiplier is a real
|
|
number that specifies the relationship between the derived unit and the
|
|
base unit using the relation below:
|
|
|
|
<br clear="all" /><table border="0" width="100%"><tr><td>
|
|
<table border="0" cellspacing="0" cellpadding="0">
|
|
<tr><td width="50%"></td><td nowrap="nowrap" align="right" colspan="1"><table border="0" cellspacing="0" cellpadding="2"><tr><td nowrap="nowrap" align="left">
|
|
<span class="roman">unit</span> </td></tr></table></td><td nowrap="nowrap" align="left">
|
|
<table border="0" cellspacing="0" cellpadding="2"><tr><td nowrap="nowrap" align="left">
|
|
= </td></tr></table></td><td nowrap="nowrap" align="left">
|
|
<table><tr><td nowrap="nowrap" align="right" colspan="1">(<span class="roman">multiplier</span> * 10<sup><span class="roman">scale</span></sup> * <span class="roman">baseUnit</span>)<sup><span class="roman">exponent</span></sup></td></tr></table></td><td width="50%"></td></tr></table>
|
|
</td></tr></table>
|
|
|
|
|
|
|
|
<center>
|
|
<img src="screenshots/units.png" alt="screenshots/units.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.3.3">
|
|
3.3.3</a> <a name="compTypes">
|
|
</a>Compartment Types</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Compartment types are used to relate multiple compartments. As shown
|
|
below, a compartment type includes an ID and an optional name field.
|
|
|
|
<center>
|
|
<img src="screenshots/compType.png" alt="screenshots/compType.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.3.4">
|
|
3.3.4</a> <a name="specTypes">
|
|
</a>Species Types</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Species types are used to relate multiple species. As shown below, a
|
|
species type includes an ID and an optional name field.
|
|
|
|
<center>
|
|
<img src="screenshots/specType.png" alt="screenshots/specType.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc3.4">
|
|
3.4</a> <a name="InitRuleConstEvent">
|
|
</a>Initial Assignments/Rules/Constraints/Events</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
The <tt>Initial Assignments/Rules/Constraints/Events</tt>
|
|
tab as shown below allows users to provide initial assignments
|
|
(see Section ),
|
|
rules (see Section ),
|
|
constraints (see Section ), and
|
|
events (see Section ).
|
|
|
|
<center>
|
|
<img src="screenshots/IRCE.png" alt="screenshots/IRCE.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.4.1">
|
|
3.4.1</a> <a name="initials">
|
|
</a>Initial Assignments</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Initial assignments as shown below are used to provide an SBML math formula
|
|
(see Section <a href="#SBMLMath">3.1</a>) that is evaluated at time 0 to determine
|
|
the initial value of a compartment size, species amount or
|
|
concentration, or parameter. The value of this formula takes precedence over
|
|
the initial value specified in the object.
|
|
|
|
<center>
|
|
<img src="screenshots/initial.png" alt="screenshots/initial.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.4.2">
|
|
3.4.2</a> <a name="rules">
|
|
</a>Rules</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
There are three types of rules: algebraic, assignment, and rate rules
|
|
which are in the following form:
|
|
|
|
<center>
|
|
|
|
<table border="1">
|
|
<tr><td align="center">Algebraic </td><td align="center">left-hand side is zero </td><td align="center">0 = f(W) </td></tr>
|
|
<tr><td align="center">Assignment </td><td align="center">left-hand side is a scalar </td><td align="center">x = f(W) </td></tr>
|
|
<tr><td align="center">Rate </td><td align="center">left-hand side is a rate-of-change </td><td align="center">[dx/dt] = f(W)
|
|
</td></tr></table>
|
|
|
|
</center>
|
|
Algebraic rules specify relationships which must be maintained
|
|
(not currently supported by analysis). Assignment rules specify
|
|
the value of a compartment size, species amount or concentration, or
|
|
parameter in terms of an SBML math formula (see
|
|
Section <a href="#SBMLMath">3.1</a>). A variable cannot be determined by
|
|
both an assignment rule and initial assignment. Rate rules specify
|
|
the rate of change of a compartment size, species amount or
|
|
concentration, or parameter in terms of an SBML math formula
|
|
(see Section <a href="#SBMLMath">3.1</a>). A variable cannot be determined
|
|
by both an assignment rule and a rate rule. A species that is
|
|
a reactant or a product of any reaction cannot be updated by either
|
|
an assignment rule or rate rule.
|
|
|
|
<div class="p"><!----></div>
|
|
When adding a rule, the user first selects the type of rule as shown
|
|
below. This
|
|
will automatically restrict the set of variables available for the
|
|
left-hand side to those that are valid. The user should then select
|
|
a variable, and enter an SBML math formula (see Section <a href="#SBMLMath">3.1</a>)
|
|
for the rule. When editing a rule, the user cannot modify the rule type.
|
|
|
|
<center>
|
|
<img src="screenshots/rule.png" alt="screenshots/rule.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.4.3">
|
|
3.4.3</a> <a name="constraints">
|
|
</a>Constraints</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Constraints are used to specify properties that should cause
|
|
simulation to terminate. Our analysis method can provide histograms
|
|
that show the proportion of simulations that are terminated due to each
|
|
possible constraint. As shown below,
|
|
each constraint is composed of an ID which is
|
|
used to identify it in these histograms, a constraint given as an
|
|
SBML math formula (see Section <a href="#SBMLMath">3.1</a>), and a message
|
|
describing the constraint. A default id is automatically generated
|
|
when a new constraint is created.
|
|
|
|
<center>
|
|
<img src="screenshots/constraint.png" alt="screenshots/constraint.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h4><a name="tth_sEc3.4.4">
|
|
3.4.4</a> <a name="events">
|
|
</a>Events</h4>
|
|
|
|
<div class="p"><!----></div>
|
|
Events are used to specify discrete changes of compartment sizes,
|
|
species amounts or concentrations, and parameter values.
|
|
As shown below, each event
|
|
is composed of an ID, an optional name, a trigger formula, an optional
|
|
delay formula, and a list of event assignments. When adding a new
|
|
event, a default ID is provided. The behavior of an event is that during
|
|
each simulation cycle, the trigger formula is evaluated. If it was false
|
|
in the previous simulation cycle, and it is now evaluating to true,
|
|
the event is scheduled to occur at a time in the future specified by
|
|
the delay formula or immediately if no delay formula is provided.
|
|
It should be noted that since the trigger value must change from false
|
|
to true, no event is scheduled if the trigger evaluates to true at the
|
|
start of simulation. When an event occurs, it executes all the event
|
|
assignments. Each event assignment sets a compartment size, species
|
|
amount or concentration, or parameter value to the value specified by
|
|
the SBML math formula (see Section <a href="#SBMLMath">3.1</a>) provided with the event
|
|
assignment.
|
|
|
|
<center>
|
|
<img src="screenshots/event.png" alt="screenshots/event.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc4">
|
|
4</a> <a name="GCMEdit">
|
|
</a>GCM Editor</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
The GCM editor shown below allows the user to create or modify a GCM
|
|
(see Section ). A GCM is a compact graphical representation
|
|
of a genetic circuit which can later be synthesized into an SBML model.
|
|
A GCM includes promoters (see Section ),
|
|
GCM species (see Section ),
|
|
influences (see Section ),
|
|
GCM parameters (see Section ), and an optional
|
|
SBML file. GCM species, influences,
|
|
and promoters can be added, removed, or edited. Parameters can only be edited.
|
|
An SBML file can also be selected to merge with the SBML generated from a GCM.
|
|
This allows either customization of the SBML model or the addition of SBML
|
|
constructs such as Initial Assignments, Rules, Constraints,
|
|
and Events (see Section <a href="#InitRuleConstEvent">3.4</a>).
|
|
|
|
<center>
|
|
<img src="screenshots/GCMedit.png" alt="screenshots/GCMedit.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
To add a new item to the GCM, click on the appropriate add button. You
|
|
will then be prompted to input information regarding the new
|
|
item. After you have filled out the required fields, click on ok
|
|
and the new item will be added into the GCM.
|
|
To remove an item from the GCM, select that item and click the
|
|
remove button. The item will then be removed from the GCM.
|
|
However, if you try to remove species or promoters that are used in
|
|
an influence, you will first have to remove the influence in
|
|
order to remove the species or promoter from the model.
|
|
To edit an existing item, select that item from the list and
|
|
click the edit button. An editing window will open and you will
|
|
be able to change the properties of that item. When you are done
|
|
editing this item, click save to save the changes to the item.
|
|
To merge an existing SBML file with the GCM output, click on
|
|
the SBML file and select the SBML file to use. This will merge
|
|
the contents of the selected SBML file with the SBML file that is
|
|
generated from the GCM. Finally, there are two abstractions that can
|
|
be selected to be performed when generating SBML, the biochemical and
|
|
dimerization abstractions.
|
|
|
|
<div class="p"><!----></div>
|
|
Once a GCM is completed, the user can save the GCM or save the GCM
|
|
using a new name. The user can also save the GCM as SBML which creates
|
|
an SBML file of the same name as the GCM. Finally, the user can save
|
|
an SBML template which creates a blank SBML file with the same species
|
|
as the GCM. This is useful for creating an SBML file which will be
|
|
attached to the GCM, and includes rules, constraints, or events.
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc4.1">
|
|
4.1</a> <a name="Promoters">
|
|
</a>Promoters</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
Promoters are special species which represent the region of the DNA
|
|
from which transcription is initiated.
|
|
When adding or editing promoters, the user must supply a unique ID.
|
|
An optional name can also be provided which is an arbitrary string
|
|
description for the promoter.
|
|
If desired, the user can then modify the initial promoter count (ng),
|
|
the RNAP binding equilibrium (Ko),
|
|
the open complex production rate (ko),
|
|
the stoichiometry of production (i.e., the number of transcripts
|
|
per mRNA, np), the basal production rate (kb), or
|
|
the activated production rate (ka).
|
|
|
|
<center>
|
|
<img src="screenshots/promoter.png" alt="screenshots/promoter.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc4.2">
|
|
4.2</a> <a name="GCMSpecies">
|
|
</a>GCM Species</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
GCM species are the molecules (usually proteins) produced by genes.
|
|
When adding or editing a species, the user must provide a unique ID.
|
|
The user can also select the type of the species to be normal, constant,
|
|
or unconstrained.
|
|
A normal species will result in gene production and degradation reactions
|
|
being produced. A constant species will not generate any
|
|
production or degradation reactions. An unconstrained species will
|
|
produce a constant production and degradation reaction.
|
|
The user can also specify an initial species count (ns), a
|
|
Dimerization equilibrium (Kd), and a degradation rate (kd).
|
|
|
|
<center>
|
|
<img src="screenshots/GCMspecies.png" alt="screenshots/GCMspecies.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc4.3">
|
|
4.3</a> <a name="Influences">
|
|
</a>Influences</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
Influences describe the relationships between the GCM species.
|
|
When adding or editing an influence, the user must select an
|
|
input and output species, as well as the type of influence. If
|
|
the type is repression, then the input species represses the
|
|
production of the output species. If the type is activation, then
|
|
the input species activates the production of the output species.
|
|
The user can also specify whether the influence has a promoter.
|
|
If a promoter is selected, then this groups all influences using
|
|
the same promoter together.
|
|
|
|
<center>
|
|
<img src="screenshots/influence.png" alt="screenshots/influence.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
For example, if there are two influences:<br />
|
|
A −| C, Promoter P1<br />
|
|
B −| C, Promoter P2<br />
|
|
this will create two reactions, where in the presence of A and
|
|
B, C is repressed. This would behave roughly like a NAND gate.
|
|
If, on the other hand, there are two influences:<br />
|
|
A −| C, Promoter P1<br />
|
|
B −| C, Promoter P1<br />
|
|
this creates one reaction, where in the presence of A or
|
|
B, C is repressed. This would behave roughly like a NOR gate.
|
|
|
|
<div class="p"><!----></div>
|
|
Users can also specify if the influence is a biochemical
|
|
influence. A biochemical influence requires all input species
|
|
belonging to the same promoter to be present in order to affect
|
|
transcription.
|
|
|
|
<div class="p"><!----></div>
|
|
For example, if there are two biochemical influences:<br />
|
|
A +| C, Promoter P1<br />
|
|
B +| C, Promoter P1<br />
|
|
this will create two reactions, A and B combines into a
|
|
complex, and the complex represses the production of C. This is a
|
|
NAND gate. If, on the other hand, if biochemical is not selected,
|
|
this behaves as a NOR gate.
|
|
|
|
<div class="p"><!----></div>
|
|
The user can also set the value for degree of cooperativity (nc)
|
|
which is the number of binding sites for transcription factors.
|
|
The N-mer as transcription factor (nd) field determines how many
|
|
monomers of the input species
|
|
must be bound together in order to affect transcription. The user
|
|
can also set the value of the repression or activation binding equilibrium
|
|
(Kr and Ka). Finally, the user can specify the biochemical equilibrium
|
|
(Kb).
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc4.4">
|
|
4.4</a> <a name="GCMParameters">
|
|
</a>GCM Parameters</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
GCM parameters are a list of global parameters that are used
|
|
when generating the SBML model for the GCM. The parameter list
|
|
allows the user an easy way to change all the parameter values in
|
|
a convenient location. If a parameter in the GCM is set to
|
|
default, it will use the value found in the GCM parameter list.
|
|
These defaults can be modified in the user preferences
|
|
(see Section ). The GCM parameters are listed below:
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<center>
|
|
<table border="1">
|
|
<tr><td align="center">ID </td><td align="center">Default Value </td><td align="center">Units </td><td align="center">Structure </td><td align="center">Description </td></tr><tr><td></td></tr>
|
|
<tr><td align="center">nr </td><td align="center">30 </td><td align="center">molecule </td><td align="center">model </td><td align="center">Initial RNAP count </td></tr>
|
|
<tr><td align="center">ns </td><td align="center">0 </td><td align="center">molecule </td><td align="center">species </td><td align="center">Initial species count </td></tr>
|
|
<tr><td align="center">Kd </td><td align="center">0.05 </td><td align="center">[1/(<span class="roman">molecule</span>)] </td><td align="center">species
|
|
</td><td align="center">Dimerization equilibrium</td></tr>
|
|
<tr><td align="center">kd </td><td align="center">0.0075 </td><td align="center">[1/(<span class="roman">sec</span>)] </td><td align="center">species
|
|
</td><td align="center">Degradation rate </td></tr>
|
|
<tr><td align="center">ng </td><td align="center">2 </td><td align="center">molecule </td><td align="center">promoter </td><td align="center">Initial promoter count </td></tr>
|
|
<tr><td align="center">np </td><td align="center">10 </td><td align="center">molecule </td><td align="center">promoter </td><td align="center">Stoichiometry of
|
|
production </td></tr>
|
|
<tr><td align="center">nc </td><td align="center">2 </td><td align="center">molecule </td><td align="center">promoter </td><td align="center">Degree of cooperativity </td></tr>
|
|
<tr><td align="center">Ko </td><td align="center">0.033 </td><td align="center">[1/(<span class="roman">molecule</span>)] </td><td align="center">promoter
|
|
</td><td align="center">RNAP binding equilibrium</td></tr>
|
|
<tr><td align="center">ko </td><td align="center">0.05 </td><td align="center">[1/(<span class="roman">sec</span>)] </td><td align="center">promoter
|
|
</td><td align="center">Open complex production rate </td></tr>
|
|
<tr><td align="center">kb </td><td align="center">0.0001 </td><td align="center">[1/(<span class="roman">sec</span>)] </td><td align="center">promoter
|
|
</td><td align="center">Basal production rate </td></tr>
|
|
<tr><td align="center">ka </td><td align="center">0.25 </td><td align="center">[1/(<span class="roman">sec</span>)] </td><td align="center">promoter
|
|
</td><td align="center">Activated production rate</td></tr>
|
|
<tr><td align="center">nd </td><td align="center">1 </td><td align="center">molecule </td><td align="center">influence </td><td align="center">N-mer as transcription
|
|
factor </td></tr>
|
|
<tr><td align="center">Kr </td><td align="center">0.5 </td><td align="center">[1/(<span class="roman">molecule</span><sup>nc</sup>)] </td><td align="center">influence
|
|
</td><td align="center">Repression binding equilibrium </td></tr>
|
|
<tr><td align="center">Ka </td><td align="center">0.0033 </td><td align="center">[1/(<span class="roman">molecule</span><sup>(nc+1)</sup>)] </td><td align="center">influence
|
|
</td><td align="center">Activation binding equilibrium </td></tr>
|
|
<tr><td align="center">Kb </td><td align="center">0.05 </td><td align="center">[1/(<span class="roman">molecule</span>)] </td><td align="center">influence
|
|
</td><td align="center">Biochemical equilibrium </td></tr></table>
|
|
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<center><img src="screenshots/GCMparam.png" alt="screenshots/GCMparam.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc5">
|
|
5</a> <a name="Analysis">
|
|
</a>Analysis View</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
The analysis view is used to analyze biochemical reaction
|
|
network models. The analysis view as shown below includes tabs for
|
|
simulation options (see Section ),
|
|
abstraction options (see Section ),
|
|
a parameter editor (see Section ),
|
|
a TSD graph editor (see Section ), and a
|
|
probability graph editor (see Section ).
|
|
|
|
<center>
|
|
<img src="screenshots/analysisView.png" alt="screenshots/analysisView.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc5.1">
|
|
5.1</a> <a name="simOptions">
|
|
</a>Simulation Options</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
iBioSim comes with a number of simulation methods, ranging
|
|
from continuous-deterministic simulation methods to
|
|
discrete-stochastic simulation methods. In order to perform
|
|
efficient temporal behavior analysis, various model abstraction
|
|
can also be automatically applied. These routines are implemented
|
|
within the reb2sac tool described in
|
|
<A HREF="http://www.async.ece.utah.edu/publications">
|
|
Kuwahara's PhD Dissertation (UofUtah 2007)
|
|
</A>
|
|
.
|
|
|
|
<div class="p"><!----></div>
|
|
The first set of radio buttons in this tab specifies the
|
|
levels of abstraction. "None" means to use no abstraction,
|
|
"Abstraction" means to perform reaction-based abstraction, and
|
|
"Logical Abstraction" means to perform both reaction-based and
|
|
logical abstractions.
|
|
|
|
<div class="p"><!----></div>
|
|
The second set of radio buttons specify the type of analysis.
|
|
"ODE" is for continuous-deterministic simulation,
|
|
"Monte Carlo" is for discrete-stochastic simulation,
|
|
"Markov" performs temporal probability distribution
|
|
analysis on finite-state Markov chain models, "sbml"
|
|
outputs the model in SBML format, "Network" outputs the
|
|
structure of the model in the GraphViz format for display by dotty,
|
|
"Browser" outputs the model in xhtml format for display
|
|
in a web browswer.
|
|
|
|
<div class="p"><!----></div>
|
|
The last set of radio buttons asks if you want to "Overwrite"
|
|
the simulation runs or if you want to "Append" more
|
|
simulation runs.
|
|
If you have not yet performed any simulation, this option is disabled.
|
|
|
|
<div class="p"><!----></div>
|
|
The next field specifies the simulation method you want to use
|
|
based on the simulation type you specified. The methods available
|
|
are:
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<center>
|
|
<table border="1">
|
|
<tr><td align="center">Type </td><td align="center">Method ID </td><td>Description </td></tr><tr><td></td></tr>
|
|
<tr><td align="center">ODE </td><td align="center">Euler </td><td>The forward Euler Method </td></tr>
|
|
<tr><td align="center">ODE </td><td align="center">gear1 </td><td>Gear Method M=1 </td></tr>
|
|
<tr><td align="center">ODE </td><td align="center">gear2 </td><td>Gear Method M=2 </td></tr>
|
|
<tr><td align="center">ODE </td><td align="center">rk4imp </td><td>Implicit 4th order Runge-Kutta at Gaussian points </td></tr>
|
|
<tr><td align="center">ODE </td><td align="center">rk8pd </td><td>Embedded Runge-Kutta Prince-Dormand (8,9) method </td></tr>
|
|
<tr><td align="center">ODE </td><td align="center">rkf45 </td><td>Embedded Runge-Kutta-Fehlberg (4, 5) method </td></tr>
|
|
<tr><td align="center">Monte carlo </td><td align="center">Gillespie </td><td>Gillespie's SSA direct method </td></tr>
|
|
<tr><td align="center">Monte carlo </td><td align="center">emc-sim </td><td>Use jump count as next reaction time </td></tr>
|
|
<tr><td align="center">Monte carlo </td><td align="center">bunker </td><td>Uses mean for next reaction time </td></tr>
|
|
<tr><td align="center">Monte carlo </td><td align="center">nmc </td><td>Uses normally distributed next reaction time
|
|
</td></tr></table>
|
|
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
There are some properties that need to be set for simulation.
|
|
The table below specifies these:
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<center>
|
|
<table border="1">
|
|
<tr><td>Field </td><td>Description </td></tr><tr><td></td></tr>
|
|
<tr><td>Time Limit </td><td>The simulation time limit </td></tr>
|
|
<tr><td>Print Interval </td><td>The print time interval for each simulation run </td></tr>
|
|
<tr><td>Maximum Time Step </td><td>The maximum time step allowed </td></tr>
|
|
<tr><td> </td><td>(also minimum time step for the Euler method) </td></tr>
|
|
<tr><td>Absolute Error </td><td>Used by the adaptive time step ODE methods </td></tr>
|
|
<tr><td>Random Seed </td><td>An integer number as a seed to generate random
|
|
numbers </td></tr>
|
|
<tr><td>Runs </td><td>The number of Monte Carlo simulation runs to
|
|
perform </td></tr>
|
|
<tr><td>Simulation ID </td><td>Creates a simulation directory with the ID name </td></tr></table>
|
|
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc5.2">
|
|
5.2</a> <a name="absOptions">
|
|
</a>Abstraction Options</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
This tab as shown below allows the user to set the properties of rapid
|
|
equilibrium, QSSA, and operator site abstraction methods.
|
|
|
|
<ul>
|
|
<li> Rapid Equilibrium Condition 1 specifies threshold T1 such that the rapid
|
|
equilibrium condition fails when T1 > E0 / (S0 + k−1/k1).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Rapid Equilibrium Condition 2 specifies threshold T2 such that the rapid
|
|
equilibrium condition fails when T1 > k2 /k−1.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> The QSSA condition specifies threshold T used by
|
|
the QSSA abstraction method where T > E0 / (S0 + KM).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> The Max concentration threshold specifies the maximum
|
|
number of molecules that a species can have initially and still
|
|
be considered an operator site by the operator site reduction.
|
|
|
|
<div class="p"><!----></div>
|
|
This tab also allows the user to select the interesting species.
|
|
Interesting species are the ones that are used in the
|
|
analysis, and hence are those which should never be abstracted away.
|
|
This tab shows all available species, and to make a species (or set of
|
|
species) interesting, highlight the species and press the Add Species
|
|
button. There is also a button to remove interesting species and to clear
|
|
all interesting species.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<center>
|
|
<img src="screenshots/absOptions.png" alt="screenshots/absOptions.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc5.3">
|
|
5.3</a> <a name="paramEdit">
|
|
</a>Parameter Editor</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
The parameter editor as shown below is similar in form to the SBML editor,
|
|
but it only allows initial concentrations and parameters to be
|
|
adjusted. Each of these parameters starts with the original value
|
|
specified in the SBML or GCM associated with
|
|
this analysis view. By changing the type to "Custom", a
|
|
new value can be entered. Changing the type back to "Original",
|
|
restores the original value. These values can also be swept by
|
|
selecting the "Sweep" type. In this case, you should
|
|
provide a start value, a stop value, a step amount, and a level
|
|
(1 or 2). When analyzing using sweep parameters, one analysis run
|
|
is produced for each value stepped through from start to stop.
|
|
The parameters at level 2 are changed first. When they have all
|
|
reached their stop value, the parameters at level 1 are stepped
|
|
once, and the parameters at level 2 are stepped through again.
|
|
This process repeats until all parameters at level 1 have stepped
|
|
to their stop value.
|
|
|
|
<center>
|
|
<img src="screenshots/paramEdit.png" alt="screenshots/paramEdit.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc6">
|
|
6</a> <a name="Learn">
|
|
</a>Learn View</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
The learn view is used to discover genetic circuit
|
|
connectivity from time series data. The learn view includes tabs
|
|
for a data manager (see Section ),
|
|
a learn tool (see Section ), and a
|
|
TSD graph editor (see Section ).
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc6.1">
|
|
6.1</a> <a name="dataManager">
|
|
</a>Data Manager</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
The data manager as shown below is used to both enter time series
|
|
experimental data as well as bring data
|
|
into the learn view. The Add button is used to create a new data
|
|
file. After pressing this button, enter the name of the new data
|
|
file, and then enter the data for this file using the data editor
|
|
to the right. The Remove button deletes all highlighted files.
|
|
Note that after highlighting one file, you can use the ctrl key
|
|
to highlight additional files or the shift key to highlight a
|
|
range of files. The Rename button is used to change the name of a
|
|
data file. The Copy button copies a data file. The Copy From View
|
|
button brings up a list of all analysis and learn views in the
|
|
current project, and data from the selected view will be copied
|
|
into this learn view. Finally, the Import button brings up a file
|
|
browser, and it allows you to import a data file from outside
|
|
this project. These files can be in time series data (TSD) format
|
|
(see Section ), comma separated value (CSV) format, or tab
|
|
delimited format (DAT).
|
|
|
|
<div class="p"><!----></div>
|
|
The contents of the data file highlighted on the left appear in the
|
|
data editor on the right. Individual data entries can be modified,
|
|
new data points can be added using the Add Data Point button, data
|
|
points can be removed using the Remove Data Point button, and data
|
|
points can be copied using the Copy Data Point button. When you are
|
|
satisfied with all your changes, you should press the Save button
|
|
to record your changes.
|
|
|
|
<center>
|
|
<img src="screenshots/dataManager.png" alt="screenshots/dataManager.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h3><a name="tth_sEc6.2">
|
|
6.2</a> <a name="learnTool">
|
|
</a>Learn Tool</h3>
|
|
|
|
<div class="p"><!----></div>
|
|
The learn tool shown below uses the GeneNet algorithm described in
|
|
<A HREF="http://www.async.ece.utah.edu/publications">
|
|
Barker's PhD dissertation (UofUtah 2007)
|
|
</A>
|
|
. To use this learn tool, adjust
|
|
any options described below, if desired, then press the Save and
|
|
Learn button. The resulting genetic circuit is specified using
|
|
our Genetic Circuit Model (GCM) Format (see Section ) and is shown
|
|
graphically using GraphViz's Dotty tool. On this tab, there are also
|
|
buttons to save the parameters without learning, view the last learned
|
|
circuit, save the generated circuit into the project, and view the last run
|
|
log.
|
|
|
|
<center>
|
|
<img src="screenshots/learn.png" alt="screenshots/learn.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
Below are the basic learning options as shown above are as follows:
|
|
|
|
<ul>
|
|
<li> Minimum Number of Initial Vectors (Tn) (default=2): <br />
|
|
Tn is a threshold value used in the CreateInfluenceVectorSet
|
|
algorithm and represents the minimum number of influence vectors
|
|
constructed in this algorithm.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Maximum Influence Vector Size (Tj) (default=2): <br />
|
|
Tj is a threshold value used in the CombineInfluenceVectors
|
|
algorithm to determine the maximal size of merged influence
|
|
vectors.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Score for Empty Influence Vector (Ti) (default=0.5): <br />
|
|
The score for an influence vector with no influences in it.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Number of Bins (default=4): <br />
|
|
The number of bins value specifies how many values the
|
|
encoded time series data can assume.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Equal Data Per Bins / Equal Spacing of Bins: <br />
|
|
This radio button selects whether the auto generated levels
|
|
should be determined by equaling dividing the data between the
|
|
bins or by equally dividing the range of the data.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Use Auto Generated Levels / Use User Generated Levels: <br />
|
|
This radio button allows the user to select whether they want
|
|
the levels separating the bins to be auto generated or the user
|
|
would like to provide them.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> When using user provided levels, the Suggest Levels
|
|
button will provide the levels that would have been auto
|
|
generated as a suggestion. These levels can then edited by the
|
|
user. The number of bins for each species can also be individually adjusted.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<div class="p"><!----></div>
|
|
The advanced learning options shown below are as follows:
|
|
|
|
<ul>
|
|
<li> Ratio for Activation (Ta) (default=1.15): <br />
|
|
A probability ratio above this value results in a vote for an
|
|
influence vector that has a majority of activation influences.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ratio for Repression (Tr) (default=0.75): <br />
|
|
A probability ratio above this value results in a vote for an
|
|
influence vector that has a majority of repression influences.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Merge Influence Vectors Delta (Tm) (default=0.0): <br />
|
|
Two influence vectors cannot be merged unless the difference
|
|
in their scores is less than this value.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Relax Thresholds Delta (Tt) (default=0.025): <br />
|
|
The values of Ta and Tr are modified by this amount when
|
|
these thresholds are relaxed.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Debug Level (default=0): <br />
|
|
This controls how much information is displayed by the
|
|
GeneNet algorithm when it runs.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Successors / Predecessors / Both (default=Successors): <br />
|
|
This radio button selects whether successor data point pairs,
|
|
predecessor data point pairs, or both are used.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Basic FindBaseProb (default=unchecked): <br />
|
|
When selected, the basic FindBaseProb function is used.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<center>
|
|
<img src="screenshots/advLearn.png" alt="screenshots/advLearn.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc7">
|
|
7</a> <a name="TSDEdit">
|
|
</a>TSD Graph Editor</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
The TSD graph editor appears as a tab in both analysis and learn
|
|
views. TSD graphs can also be created at the top-level of the project
|
|
to allow you to integrate results from several analysis or learn
|
|
views. These graphs can be created using the New → TSD Graph
|
|
menu option. Once created, they can be viewed and edited by double
|
|
clicking on the graph in the project window. An example graph is
|
|
shown below.
|
|
|
|
<center>
|
|
<img src="screenshots/TSDgraph.png" alt="screenshots/TSDgraph.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
In the TSD graph editor shown below,
|
|
a graph is created by double clicking on the graph. You can then set
|
|
various parameters and select what values you would like to have
|
|
graphed. The parameters that you can select for a graph include:
|
|
|
|
<ul>
|
|
<li> Title - The title of the graph.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> X-Axis Label - The label displayed for the x-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Y-Axis Label - The label displayed for the y-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> X-Min - The starting value for the x-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> X-Max - The ending value for the x-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> X-Step - The increment for the x-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Y-Min - The starting value for the y-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Y-Max - The ending value for the y-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Y-Step - The increment for the y-Axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Auto Resize Check Box -
|
|
Determines whether to automatically resize the graph for best fit.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<center>
|
|
<img src="screenshots/editGraph.png" alt="screenshots/editGraph.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
The data selection menu on the left displays all of the
|
|
available sets of data that can be graphed. In particular, one can
|
|
graph the average, variance, standard deviation, or results from
|
|
individual simulation runs. For a top-level graph, these
|
|
data sets will be organized hierarchically. Hierarchy is also
|
|
introduced when simulations in an analysis view are given
|
|
simulation IDs or after performing an analysis while sweeping parameter
|
|
values. After selecting a data set, one can select individual species to
|
|
graph and how they are to be displayed. In other words, for each
|
|
species, there are the following options:
|
|
|
|
<ul>
|
|
<li> Use Check Box - Determines
|
|
whether or not this species is displayed on the graph. Checking or
|
|
unchecking the box at the top changes the state for all species in
|
|
the data set.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Species Label - The name displayed in the legend.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Drop Down Menu Of Colors - The color that is used for this species.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Drop Down Menu Of Shapes - The shape that is used to mark the
|
|
data points.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Connect Check Box -
|
|
Determines whether to connect the points with a line. Checking or
|
|
unchecking the box at the top changes the state for all species in
|
|
the data set.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Visible Check Box - Determines
|
|
whether shapes are visible on the line. Checking or
|
|
unchecking the box at the top changes the state for all species in
|
|
the data set.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Fill Check Box - Determines whether shapes are filled
|
|
on the line. Checking or
|
|
unchecking the box at the top changes the state for all species in
|
|
the data set.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
Note that a check mark appears on a data set to indicate that some
|
|
species have been selected in that data set. Also, all species can
|
|
be deselected by pressing the Deselect All button.
|
|
|
|
<div class="p"><!----></div>
|
|
The "Save Graph" button saves the settings for the graph to
|
|
a file, so when you re-open the graph, it will reload this data and display
|
|
in the same way as before. The "Save As" button prompts for a
|
|
filename and creates a new top-level graph with that name.
|
|
Finally, the "Export" button prompts for a filename and exports
|
|
the data to the given name. The extension provided for the filename
|
|
is used to determine how the graph is to be exported. The
|
|
supported file types are:
|
|
|
|
<ul>
|
|
<li> csv - comma separated value data file.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> dat - column separated data file.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> eps - encapsulated postscript.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> jpg - JPEG (Joint Photographic Experts Group).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> pdf - portable document format.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> png - portable network graphics.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> svg - scalable vector graphics.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> tsd - time series data format (see Section ).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
If no extension is given, then the file type is the one
|
|
specified in the file filter (default is pdf). For image (i.e.,
|
|
not data) file types, you will be prompted to give a desired
|
|
pixel height and width for the file before the file is exported.
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc8">
|
|
8</a> <a name="ProbEdit">
|
|
</a>Probability Graph Editor</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
Probability graphs are used to display histograms for reasons that
|
|
simulations terminated. This is used in conjunction with SBML constraints
|
|
to determine the likelihood of various conditions.
|
|
The probability graph editor appears as a tab in analysis
|
|
views. Probability graphs can also be created at the top-level of the project
|
|
to allow you to integrate results from several analysis views.
|
|
These graphs can be created using the New → Probability Graph
|
|
menu option. Once created, they can be viewed and edited by double
|
|
clicking on the graph in the project window. An example probability
|
|
graph is shown below.
|
|
|
|
<center>
|
|
<img src="screenshots/probGraph.png" alt="screenshots/probGraph.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
In the probability graph editor,
|
|
a graph is created by double clicking on the graph. You can then set
|
|
various parameters and select what values you would like to have
|
|
graphed. The parameters that you can select for a graph include:
|
|
|
|
<ul>
|
|
<li> Title - The title of the graph.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> X-Axis Label - The label displayed for the x-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Y-Axis Label - The label displayed for the y-axis.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<center>
|
|
<img src="screenshots/editProbGraph.png" alt="screenshots/editProbGraph.png" />
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
The data selection menu on the left displays all of the
|
|
available sets of data that can be graphed.
|
|
For a top-level graph, these
|
|
data sets will be organized hierarchically. Hierarchy is also
|
|
introduced when simulations in an analysis view are given
|
|
simulation IDs or after performing an analysis while sweeping parameter
|
|
values. After selecting a data set, one can select individual constraints to
|
|
graph and how they are to be displayed. In other words, for each
|
|
constraint, there are the following options:
|
|
|
|
<ul>
|
|
<li> Use Check Box - Determines
|
|
whether or not this constraint is displayed on the graph. Checking or
|
|
unchecking the box at the top changes the state for all constraints in
|
|
the data set.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Constraints Label - The name displayed in the legend.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Drop Down Menu Of Colors - The color that is used for this constraint.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
Note that a check mark appears on a data set to indicate that some
|
|
constraints have been selected in that data set. Also, all constraints can
|
|
be deselected by pressing the Deselect All button.
|
|
|
|
<div class="p"><!----></div>
|
|
The "Save Graph" button save the settings for the graph to
|
|
a file, so when you re-open the graph, it will reload this data and display
|
|
in the same way as before. The "Save As" button prompts for a
|
|
filename and creates a new top-level graph with that name.
|
|
Finally, the "Export" button prompts for a filename and exports
|
|
the data to the given name. The extension provided for the filename
|
|
is used to determine how the graph is to be exported. The
|
|
supported file types are:
|
|
|
|
<ul>
|
|
<li> eps - encapsulated postscript.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> jpg - JPEG (Joint Photographic Experts Group).
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> pdf - portable document format.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> png - portable network graphics.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> svg - scalable vector graphics.
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
If no extension is given, then the file type is the one
|
|
specified in the file filter (default is pdf). For image (i.e.,
|
|
not data) file types, you will be prompted to give a desired
|
|
pixel height and width for the file before the file is exported.
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc9">
|
|
9</a> <a name="Preferences">
|
|
</a>Preferences</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
User preferences can be set by selecting the <tt>Preferences</tt> option
|
|
under the <tt>File</tt> menu on Linux and Windows or the <tt>iBioSim</tt>
|
|
menu on MacOS. As shown below, the user can decided whether they wish
|
|
to see warnings about undeclared units in SBML and whether they wish
|
|
to check units at all. The user can also change the GCM default
|
|
parameter values by clicking on the <tt>GCM Defaults</tt> button.
|
|
|
|
<center>
|
|
|
|
<table>
|
|
<tr><td align="center"><img src="screenshots/SBMLPref.png" alt="screenshots/SBMLPref.png" /> </td><td align="center"><img src="screenshots/GCMPref.png" alt="screenshots/GCMPref.png" />
|
|
</td></tr></table>
|
|
|
|
</center>
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc10">
|
|
10</a> <a name="GCM">
|
|
</a>Genetic Circuit Model Format</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
Our genetic circuit model (gcm) format specifies a genetic
|
|
circuit using the same format used by the GraphViz graph drawing
|
|
tool. The vertices in the graph are the species in
|
|
the genetic circuit, and the edges in the graph represent the
|
|
activation and repression relationships between the species. An
|
|
activation relationship is shown with a blue (blue4) arrow (vee)
|
|
and a repression relationship is shown with a red (firebrick4)
|
|
tee. The label field in the species declaration is the name of
|
|
the species. The arrowhead field in the relationship declaration
|
|
represents the type of relationship between the species.
|
|
Repression is labeled with a tee and activation is labeled with a
|
|
vee. The label field in the relationship declaration represents
|
|
how many molecules are necessary to activate or repress the
|
|
production of the species. An example is shown below for a simple
|
|
genetic circuit in which the species CI represses CII while CII
|
|
activates CI production. The s1 − > s2 edge has a label field of
|
|
"2" which means two molecules of CI are required to form a dimer
|
|
to repress CII.
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<pre>
|
|
digraph G {
|
|
CI [shape=ellipse,color=black,label="CI"];
|
|
CII [shape=ellipse,color=black,label="CII"];
|
|
CII -> CI [color="blue4",arrowhead=vee];
|
|
CI -> CII [color="firebrick4",label="2",arrowhead=tee];
|
|
}
|
|
|
|
</pre>
|
|
|
|
<div class="p"><!----></div>
|
|
More advanced behavior can be modeled by using extra fields.
|
|
The promoter field groups a set of species together. The examples
|
|
below shows how the promoter field works. In the genetic circuit
|
|
model below, species A represses the production of species B and
|
|
C, independently. If there was exactly 1 molecule of species A,
|
|
it would only be able to repress production of species B or C,
|
|
but not both.
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<pre>
|
|
digraph G {
|
|
A [shape=ellipse,color=black,label="A"];
|
|
B [shape=ellipse,color=black,label="B"];
|
|
C [shape=ellipse,color=black,label="C"];
|
|
A -> B [color="blue4",arrowhead=tee];
|
|
A -> C [color="blue4",arrowhead=tee];
|
|
}
|
|
|
|
</pre>
|
|
|
|
<div class="p"><!----></div>
|
|
With the promoter field, one species A now represses the
|
|
promoter "P1", which produces both species B and C.
|
|
This means that one molecule of species A will repress the
|
|
production of both species B and C.
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<pre>
|
|
digraph G {
|
|
A [shape=ellipse,color=black,label="A"];
|
|
B [shape=ellipse,color=black,label="B"];
|
|
C [shape=ellipse,color=black,label="C"];
|
|
A -> B [color="blue4",arrowhead=tee,promoter="P1"];
|
|
A -> C [color="blue4",arrowhead=tee,promoter="P1"];
|
|
}
|
|
|
|
</pre>
|
|
|
|
<div class="p"><!----></div>
|
|
The promoter field can also be used to separate production
|
|
reactions. In the example below, both species A and B can repress
|
|
the production of species C. If either is present, then very
|
|
little C will be produced. This behavior is like a NOR gate.
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<pre>
|
|
digraph G {
|
|
A [shape=ellipse,color=black,label="A"];
|
|
B [shape=ellipse,color=black,label="B"];
|
|
C [shape=ellipse,color=black,label="C"];
|
|
A -> C [color="blue4",arrowhead=tee];
|
|
B -> C [color="blue4",arrowhead=tee];
|
|
}
|
|
|
|
</pre>
|
|
|
|
<div class="p"><!----></div>
|
|
However, if there needs to be two different sources of
|
|
production for species C, the promoter field can be used to
|
|
accomplish this. In the example below, A represses the production
|
|
of C by binding to the P1 promoter, and B represses the
|
|
production of C by binding to the P2 promoter. Both A and B need
|
|
to be present to fully repress the level of C. If either is at a
|
|
low level, then the level of C will be high. This behavior is
|
|
like a NAND gate.
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<pre>
|
|
digraph G {
|
|
A [shape=ellipse,color=black,label="A"];
|
|
B [shape=ellipse,color=black,label="B"];
|
|
C [shape=ellipse,color=black,label="C"];
|
|
A -> C [color="blue4",arrowhead=tee,promoter="P1"];
|
|
B -> C [color="blue4",arrowhead=tee,promoter="P2"];
|
|
}
|
|
|
|
</pre>
|
|
|
|
<div class="p"><!----></div>
|
|
The example below shows how to model an AND gate. The species
|
|
A and B have the constant flag set to true. This means that A and
|
|
B have no production and degradation reactions. The reactions
|
|
contain a promoter label "P1". This means that the
|
|
species C can be activated by both A and B. Combined with the
|
|
type flag of biochemical, this creates a biochemical reaction
|
|
where species A and B combine together to form a complex to
|
|
activate production of species C.
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<pre>
|
|
digraph G {
|
|
A [shape=ellipse,color=black,label="A",const=true];
|
|
B [shape=ellipse,color=black,label="B",const=true];
|
|
C [shape=ellipse,color=black,label="C"];
|
|
A -> C [color="blue4",arrowhead=vee,promoter="P1",type=biochemical];
|
|
B -> C [color="blue4",arrowhead=vee,promoter="P1",type=biochemical];
|
|
}
|
|
|
|
</pre>
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc11">
|
|
11</a> <a name="TSD">
|
|
</a>Time Series Data Format</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
The time series data (tsd) format is composed of a
|
|
parenthesized and comma-separated set of time points. Each time
|
|
point is composed of a parenthesized and comma-separated set of
|
|
data for that time point. This first time point is composed of a
|
|
set of strings that are the labels for the data entries. The
|
|
first entry in each time point is by convention the time for that
|
|
time point. Below is an example simulation of the species CI and
|
|
CII from 0 to 1000 seconds with time points separated by 100
|
|
seconds.
|
|
|
|
<div class="p"><!----></div>
|
|
(("time","CI","CII"), (0,0,0), (100,0,19), (200,20,25), (300,19,18),
|
|
(400,17,20), (500,17,46), <br />
|
|
(600,26,40), (700,43,43), (800,63,28), (900,72,34), (1000,72,28))
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc12">
|
|
12</a> <a name="HotKeys">
|
|
</a>List of Hot Keys</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
Below is a list of the hot keys used in Windows and Linux with the
|
|
MacOS equilvalents in parantheses.
|
|
|
|
<ul>
|
|
<li> Ctrl-X (Cmd-Q) - Exit or quit
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-, (Cmd-,) - Preferences
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-A - About
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-M - Manual
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> (Cmd-H) - Hide window
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> (Alt-Cmd-H) - Hide other windows
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-C - Copy
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-R - Rename
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-D - Delete
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-P - New Project
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-O - Open Project
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-G - New Genetic Circuit Model
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-S - New SBML Model
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-V - New VHDL
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-L - New LHPN
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-N - Import Genetic Circuit Model or LHPN
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-B - Import SBML
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-H - Import VHDL
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-T - TSD Graph
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> Ctrl-Y - Probability Graph
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc13">
|
|
13</a> Tutorial</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
A detailed
|
|
<a href="tutorial.html">
|
|
tutorial
|
|
</a>
|
|
is available in the <tt>docs</tt> directory that comes with the distribution.
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc14">
|
|
14</a> Reporting Bugs and Feature Requests</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
In order to report a bug or to request a change or feature, please
|
|
send an email to:<br />
|
|
<a href="mailto:atacs-bugs@vlsigroup.ece.utah.edu">
|
|
<tt>atacs-bugs@vlsigroup.ece.utah.edu</tt>.<br />
|
|
</a>
|
|
The subject line must begin with one of the following keywords or the
|
|
mail will be filtered by our spam filters:
|
|
|
|
<ul>
|
|
<li> BUG - error or crash of the software
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> CHANGE - something which can be improved
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
|
|
<li> FEATURE - something new
|
|
<div class="p"><!----></div>
|
|
</li>
|
|
</ul>
|
|
|
|
<div class="p"><!----></div>
|
|
<h2><a name="tth_sEc15">
|
|
15</a> Credits</h2>
|
|
|
|
<div class="p"><!----></div>
|
|
The iBioSim tool is being developed at the University of Utah
|
|
by
|
|
<A HREF="http://www.async.ece.utah.edu/~myers">
|
|
Chris Myers,
|
|
</A>
|
|
|
|
<A HREF="http://www.cs.utah.edu/~barkern">
|
|
Nathan Barker,
|
|
</A>
|
|
|
|
<A HREF="http://www.cs.utah.edu/~kuwahara">
|
|
Hiroyuki Kuwahara,
|
|
</A>
|
|
|
|
<A HREF="http://www.async.ece.utah.edu/~cmadsen">
|
|
Curtis Madsen,
|
|
</A>
|
|
and
|
|
<A HREF="http://www.cs.utah.edu/~namphuon">
|
|
Nam Nguyen.
|
|
</A>
|
|
Nathan Barker is now with Southern Utah University, and Hiroyuki
|
|
Kuwahara is now with the Centre for Computational and System
|
|
Biology in Trento, Italy.
|
|
|
|
<div class="p"><!----></div>
|
|
|
|
<br /><br /><hr /><small>File translated from
|
|
T<sub><font size="-1">E</font></sub>X
|
|
by <a href="http://hutchinson.belmont.ma.us/tth/">
|
|
T<sub><font size="-1">T</font></sub>H</a>,
|
|
version 3.81.<br />On 10 Jan 2013, 14:10.</small>
|
|
</html>
|