Applying the Scientific Method to Simulation Experiments …

I’ve just finished a one hour Rosa & Co webinar, and thought to post the slides below. You might also be interested in their other webinars, you can find the webinar archive here.

Applying the Scientific Method from Frank Bergmann

SED-ML Level 1 Version 2–Release Candidate

The COMBINE meeting has just started, and we finally made the release candidate for the SED-ML Level 1 Version 2 specification available. SED-ML L1V2 finally extends the simulation experiments covered by SED-ML to include any kind of repeat and perturbation experiment. Apart from that it also includes the possibility to fully parameterize simulations, by specifying algorithm specific parameters like relative and absolute tolerances of integrators. The specification is available online from:

http://tinyurl.com/sed-ml-l1v2-rc

On my end I’ve updated the libSedML, and the SED-ML Script editor and of course SBW to be able to simulate L1V2. Another major change has been applied to the SED-ML Web Tools that now also support L1V2, and are now also capable of simulating the repeatedTask concept with CellML additionally to SBML.

As always any feedback is appreciated.

SBML Layout Specification RC2

Finally, after a good 10 years since the first presentation of a layout extension to SBML, the specification has been sent to the SBML editors for approval. One might think it is actually quite easy to describe where something is, and it should not take all that long to agree on a bare minimum for a standard, but be that as it may, we are now in the final stretches. If you like, you could have a look at the specification:

SBML Layout Specification RC2

It is of course fully supported by libSBML. Now that the specification is in the approved format for L3 packages, including a whole number of validation rules, validation is currently added to libSBML and will be available from the Online Validator with the acceptance of the package. In the meantime you could use the

SBML RNG Online Validator

Software support is shaping up: SBW has been supporting SBML Layout since 2005, and COPASI has it enabled in publicly released builds since last year. Both software tools also import CellDesigner annotations! At last years HARMONY meeting the layout specification has received its biggest change, by adding a GeneralGlyph, that makes it possible to also layout elements, that previously where not possible. Support for that is available in the latest SBW builds,

SBML Online Layout Viewer

And within the COPASI codebase, to be released sometime soon.Here a screenshot, showing the exchange between COPASI & SBW of an SBML Level 3 model with a GeneralGlyph that represents an SBML Event, including Trigger and Event Assignment:

SED-ML Web Tools & COMBINE archive

A couple of days I've published the COMBINE archive project to github. Today, I'm proud to let you know, that you can now upload / download COMBINE archive also to the SED-ML web tools:

  http://sysbioapps.dyndns.org/SED-ML_Web_Tools/

If you rather try it offline on your Windows box, try the SED-ML Script editor:

  SetupSedML-win32-1.11.exe

SED-ML Nested Proposal V3

A new version of the nested proposal is available immediately from:

http://identifiers.org/combine.specifications/sed-ml.proposal.nested-simulations.FB.version-3

The new version rephrases the Nested Simulation Class as Repeated Task, and addresses comments made by the community over the past couple of months (and of course the discussions at HARMONY 2012). As far as the scope is concerned, the current proposal is capable of describing all experiments possible with the previous version. Additionally through a new listOfSubTasks additional experiments can be run.

Steady state scan
Pulsing a parameter during a simulation
Multiple Stochastic Traces
Timecourse scan
2D Steady State scan

 

Of course there also is an implementation available in the SED-ML Web Tools, where all examples can be run directly.

SED-ML Nested Simulation Proposal v2

With the start of the new year it is time to get the Nested Simulation Proposal for SED-ML ready for wide-spread adoption. I believe nested simulations are vital for SED-ML so that we can cover a much larger variety of simulation experiments. I think it is especially important NOT to create a new simulation class for every single different simulation we perform on a model. By just defining two simulation classes:

• One Step: which brings the model to the next desired output step.
• Nested Simulation: which allows running over another simulation task, while changing multiple models parameters with computed values from ranges.

it is possible to construct a large number of simulations that are currently carried out.  I’ve taken these past weeks to fully flesh out all the details and the document is now available from Nature Proceedings:

http://precedings.nature.com/documents/4257/version/2

The new version describes in detail all attributes and elements and features a number of examples (see below)

All features have been implemented in libSedML. The major change is that internally libSedMLRunner no longer produces a simple 2d array of data, but a NuML result set.

NOTE: This proposal only covers the generation of the data, not the visualization. In other words this proposal allows to generate n-dimensional data sets, while currently our DataGenerators can not access the values. I believe the two issues should be handled in different proposals.

Examples

Just a brief overview of the examples:

Steady state scan
Pulsing a parameter during a simulation
Multiple Stochastic Traces
Timecourse scan
2D Steady State scan

 

Availability

As indicated above, the proposal is implemented in libSedML, a also released a new version of the SED-ML Web Tools, that can simulate all of the above examples.

Just for completeness sake: here the link to the old version:

Doc:            http://precedings.nature.com/documents/4257/version/1
Examples:   http://frank-fbergmann.blogspot.com/2010/03/nested-simulation-experiments.html

New SBML Translator Application online!

As second application I’m glad to announce the new SBML Translator application:

http://sysbioapps.dyndns.org/Translator

The application is a major redesign from the basic version.  Its features:

• multiple file upload (with drag & drop for chrome and firefox)
• translation of files via URL
• pasting of SBML
• Syntax Highlighting of the result
• downloading of translation with proper mime-type / extension

The translators have been updated to ensure that assignment rules  are sorted correctly in the translation (an issue that seems to have caused problems in the past). As soon as the SBFC project comes along I plan to include their translators as well. As always a screencast says more than words:

As always I’d love to hear any feedback that you have!

Introducing sysbioapps/Layout

Ever since the SBW applications have been pulled from sys-bio.org and are only available via IP I am working on a new version for each of these applications. Today I’ve made the new version of my Layout web application available:

http://sysbioapps.dyndns.org/Layout 

See it live:

Features

The new application has the same basic features as the old one:

• upload of an SBML file
• displaying SBML Layout / SBML Render Format
• displaying JDesigner / JDesigner 2 / CellDesigner annotation
• generating a layout
• exporting images / SVG / PDF

New in this version:

• multiple file support
• Chrome / Firefox: upload multiple files
• Chrome / Firefox: drag and drop files onto the web site to upload
• support for SBGN-ML

Implementation

The new version has been implemented using ASP.NET MVC3  and JQuery / JQueryUI. The actual heavy lifting is performed by the SBML Layout Library. The PDF export is made possible through sbml2tikz, followed by a compilation by pdflatex.

As always any feedback is welcome.

SED-ML Web Tools & KISAO

SED-ML uses KISAO to annotate simulation algorithms with information of what kind of simulation should be performed. Until today the SED-ML Web Tools only displayed the term identifier. This has changed, now the terms will be resolved and displayed:

To make this work I’ve modified LibSedML to resolve all KISAO terms found. This is now part of the Algorithm object, and can be accessed through the Term property.

Unfortunately KISAO is now only available in OWL format. This means people have to ‘reason’ over the document in order to find out even the most basic things. While the EBI provides a ‘libKISAO’, this library is only available for Java. 

In the end I’ve decided to convert the OWL file periodically in a more readable format:

 <term id='KISAO:0000377' 
        name='one-step method'>
   <definition> <![CDATA[A numerical method 
     for differential equations which uses one 
     starting value at each step.]]>
   </definition>

   <similarTo>KISAO:0000020</similarTo>
   ...
   <similarTo>KISAO:0000031</similarTo>




   <ancestor>KISAO:0000000</ancestor>

   <descendent>KISAO:0000261</descendent>
   <descendent>KISAO:0000380</descendent>
   <descendent>KISAO:0000064</descendent>
   <descendent>KISAO:0000286</descendent>
 </term>

I will update that file periodically and have it compiled into libSedML, if you would like to have a look at it, you can access it here:

kisao.xml

sys-bio.org web applications down

The web site of the Saurolab was moved to a different machine the domain sys-bio.org has been transferred to that machine. As a result, all applications that previously ran on sys-bio.org are no longer available via their old URLs. The old server is still available via its IP:

http://128.208.17.26/

That web site also still hosts the web applications:

• Layout: http://128.208.17.26/Layout/
• Simulation: http://128.208.17.26/Simulation2005/
• Translation: http://128.208.17.26/SBMLTranslator/
• Web Services: http://128.208.17.26/SbwWebServiceCreatorInterface/

In the coming weeks I will update these applications and move them over to http://sysbioapps.dyndns.org.

SBGN-ML Render Comparison

SBGN-ML, the markup language developed as part of the libSBGN project, is nearing it’s Milestone 2 release. The SBML Layout library currently fully implements the Process Diagram notation of SBGN-ML. (Work on implementing Activity Flow / Entity Relationship diagrams has started but is not anywhere close to ready.)

This is to announce a new online application:

http://sysbioapps.dyndns.org/RenderComparison/

This is how the page looks:

The site displays all current SBGN files from ProcessDiagram, ActivityFlow and EntityRelationship. Only the SBMLLayout column will be rendered every time. Information from PathVisio and SBGN-ED are cached and updated periodically.

You can change the directory, that is being displayed by selecting the Customize button on the top of the page, these options are available:

Where a different URL can be chosen (you could for example display the examples from Milestone 1 or the general examples). You also can display or hide individual columns.

As last option you can directly upload or point to any URL of an SBGN file that should be rendered.

More at COMBINE …

SBML Software Index on http://sysbioapps.dyndns.org

I’ve spend the weekend to update the sysbioapps website. It does provide a bit more information now and I’ve also fixed a minor issue with testing the SED-ML web services. Most notably however, I have placed the SBML Software Index online:

http://sysbioapps.dyndns.org/SoftwareMatrix

The Software Index provides the information from the SBML Software Survey (that collects information about available software that supports SBML) using the PivotViewer. This makes it possible to ask specific questions about the software and find the information much faster than it would be possible with the static matrix / summary information that was available until now.

I am well aware of the fact that many in the Systems Biology community do not consider Silverlight to be a viable platform: I have been told to rewrite the solution in Flash or JavaScript to make it possible to run it on more devices. However, I lack the time to do so at this moment, and so provide this information in the hopes that it will be of use to some.

How to use the Index

On the left hand side you will find a panel with the available categories:

Where you can simply search for specific information, or select options from the categories (in the screenshot above: Category, Dependencies, … SBML Import/Export) you are interested in. Each category contains several options (above we see Import and Export listed for the SBML Import / Export category). According to the pivot guidelines options within a category are supposed to be orthogonal. Unfortunately that is not the case for SBML software (as there are packages that support Import and Export for example). I still chose to place them together into one category (otherwise the number of categories would have become unwieldy). The consequence of this is that when you select both checkboxes, queries will be of the form:

SELECT TOOLS WITH EITHER SBML IMPORT  _ O R _ SBML EXPORT

rather than

SELECT TOOLS WITH EITHER SBML IMPORT _ A N D _ SBML EXPORT.

With this in mind I believe it is still possible to query the data easily (although I’m aware of at least 2 people that would disagree with this statement). I will revisit this as soon as Silverlight 5 is released this promises a modification of that behavior.

I also would like to attract your attention to the controls on the top of the control:

this allows to configure how the information is displayed. You can choose to display the information either tiled to see all selected tools at a glance:

Or as a bar graph, which makes it easy to compare specific aspects of the tools (such as which tools are available on which platform):

I will continue to update the index whenever new entries are submitted.

KNOWN ISSUES

Unfortunately at the time of this writing it was not possible to run the site using Moonlight. I know that the mono team is working tirelessly and so hope that this will be resolved in due time. Until then the index is only available on OSX and Windows. I’m sorry for the inconvenience.