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BioModels Workshop 2009: Day 2

Today was great fun – lots of presentations and lots of lively discussions, of which we were all a part, but which Nicolas Le Novère ("shown" left, courtesy of Falko Krause 🙂 ) also enjoyed.

Here are the notes!

CellML: Catherine Lloyd

Most of the talk aligned with the talk Catherine gave at BioSysBio 2009 this past week. Some parts were new, however. For instance, she seemed to spend a little more time on versioning. A version is an update of a model entry – usually with a traceable model history. A variant is a slightly different model from the same reference. A variant could be the same model adapted for adifferent cell type. Alternatively, variants of a model may be created to reproduce the different figures from a publication.

libAnnotationSBML: Neil Swainston

Automatic Linking of MIRIAM Annotation to a model using web services. He was involved with the creation of the SBML metabolic yeast network, which had MIRIAM annotations. And now that this qualitative information has been published, they're doing some experiments to get quantitative data. They developed a simple CellDesigner plugin as proof-of-concept to allow the linking of a model to their quantitative data repository (not finished yet).

MIRIAM annotations are a form of tagging the model. However, they want to do more: use the annotations to "reason" over the model. By "reason", they mean doing more than just seeing if the model is annotated: but seeing if the model is being annotated well. Do the reactions balance? Such a question cannot solely be answered by libSBML, and they can use ChEBI to do this. As a human, you would go to the ChEBI entry and get the formula from ChEBI. Then, you can compare that to your reaction. Can this be done automatically?

libAnnotationSBML connects to ChEBI, KEGG, UniProt, MIRIAM. This information is presented in a single convenience class. This stuff has a "SBML Reaction Balance Analyser". They don't do any automatic corrections, but they can identify where something doesn't match with ChEBI. Would like to do it automatically in the near future. Would also like to suggest corrections to existing models (incorrect annotations, missing reactants / products, stoichiometry). Would like to intelligently generate models.

Future: support more web services, write it in C++, or perhaps ask the MIRIAM people to have a web service method that retrieves the URL for the wsdl as well as the human-readable URL. However, connections to web services tend to be inconsistent, and therefore you can't always get the information you want.

semanticSBML: Falko Krause

You can find more information here: http://sysbio.molgen.mpg.de/semanticsbml/. Here there is a standalone GUI which is capable of offline annotation. There is also a web interface.

This is in fact a much more interesting application than is suggested by the notes – mainly I was preoccupied with making sure my talk was ready to go, as it was almost my turn. I highly recommend that you have a look at the link above and have a play with this software.

Saint

I didn't speak directly about Saint, as I will be speaking about MFO instead this afternoon. However, as model annotation was being talked about today, I thought it might be useful for me to put up some information about Saint. The presentation and video will be up on the IET website (but isn't yet). In the meantime, here's a rundown of the purpose of Saint.

The creation of accurate quantitative Systems Biology Markup Language (SBML) models is a time-intensive manual process. Modellers need to know and understand both the systems they are modelling and the intricacies of SBML. However, the amount of relevant data for even a relatively small and well-scoped model is overwhelming. Saint, an automated SBML annotation integration environment, aims to aid the modeller and reduce development time by providing extra information about any given SBML model in an easy-to-use interface. Saint accepts SBML-formatted files and integrates information from multiple databases automatically. Any new information that the user agrees with is then automatically added to the SBML model.

The initial functionality of Saint allows the annotation of already-extant species and suggests additional interactions. The user uploads their SBML model, and the portions of the model recognized by Saint are then displayed using a tabular structure. The user can then remove any items they are not interested in annotating. For instance, some terms such as "sink" are modelling artefacts and do not correspond to genes or proteins. Therefore, the user would normally wish to delete this from the search space to prevent any possible matches with actual biological species of a similar name. Once the user is satisfied with the list of items to be annotated, the model is submitted using the "Annotate Listed Items" button at the bottom of the table. A summary of the annotation returned by Saint is then added to the main table. The user can then remove any new annotation that is unsuitable for their model. At any stage, the user may click on the "Annotated Model" tab in Saint, which adds all new annotation to the original model and presents the new SBML model for viewing and download.

While there are a number of tools available for manipulating and validating SBML (e.g. LibSBML), simulating SBML models (e.g. BASIS and the SBML Toolbox ), and analysing simulations (e.g. COPASI,), and running modelling workflows (e.g. Taverna ), Saint is the first to provide basic automatic annotation of SBML models in an easy-to-use GUI. The purpose of Saint is to aid the researcher in the difficult task of information discovery by seamlessly querying multiple databases and providing the results of that query within the SBML model itself. By providing a modelling interface to existing data integration resources and, modellers are able to add valuable information to models quickly and simply.

Saint already generates reactions and associated new species and species references. It is being extended this creation of reactions to also generate skeleton models based around a species or pathway of interest.

SBO: Nick Juty

The sourceforge website has a tracker as well as access to the whole project. You can browse the whole tree from http://www.ebi.ac.uk/sbo. Your search retrieves a series of tables, and they will retrieve obsolete terms so that you can tell what used to be there. The main curation works happens via a web interface that directly talks to the database (this is just for curation). Lots of web services available.

From SBML to SBGN through SBO: Alice Villeger

Semantic annotations as a bridge between standards. Showed a very nice modification to the SBGN reference card where she colored sections by their SBO branch, which then showed up areas where different branches were used for the same type of notation (and therefore were candidates for modification within SBO). She showed that the SBML info needed is in Species Reference => this can be solved by changing the current SBGN specs. Further, there are some SBO terms that have no direct SBML equivalent (e.g. or, and). She gave a number of other examples, too.

It also seems that the compartment in SBGN and the SBML specification don't match. This is because the SBML compartment is not intended to be the same as the SBGN compartment (a functional versus a physical compartment).

Her analysis of the alignment of SBGN and SBO showed up a number of inconsistencies. This was really useful. There should be some machine-readable expression of SBML x SBO and SBGN x SBO. Further, there aren't many models annotated with
SBO yet. And, if they are, they are not always sufficiently precise. One solution could be a MIRIAM to SBO converter program.

http://arcadiapathways.sourceforge.net

http://biomodels.net/meetings/2009/index.html

Please note that this post is merely my notes on the presentation. They are not guaranteed to be correct, and unless explicitly stated are not my opinions. They do not reflect the opinions of my employers. Any errors you can happily assume to be mine and no-one else's. I'm happy to correct any errors you may spot – just let me know!

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BioModels Workshop 2009: Day 1

BioModels Database Introduction: Nicolas Le Novere

Repository of quantitative models only for the moment: no implicit statement of biochemical accuracy as a consequence of being in the database, but must be of biological interest and only those that have been described in peer-reviewed scientific literature. In terms of curation: model syntax and semantics are checked; and then models are simulated to check the correspondence to the reference; model components are annotated; they improve identification and retrieval. Models are accepted in various formats, and exported in other formats too.

The models come from individuals, existing model repositories, journals, and direct curation from literature by BioModels curators. Within the individuals category, submitters are members of the SBML community and authors. More than 200 journals *advise* deposition, including all PLoS, BMC, and Nature Mol Sys Bio.

BioModels Database Technical Aspects: Chen Li

The infrastructure of the db includes a set of tomcat application server clusters. MySql databases sit behind these server clusters. There is also a mirror site at Caltech. All models in the BioModels database have to pass through the BioModels pipeline: syntax check, consistency check, divergence to either curated or non-curated branch. When a model is submitted, the db parses it and fetches MIRIAM anntoations. It fetches information from GO, UP, ChEBI, and the taxonomy db, and then added into the model. Exports are available in lots of formats: most of the SBML levels, CellML, XPP-Aut, VCell, SciLab, BioPax. For BioPax and VCell they use a Java converter developed in-house; for CellML, SciLab and XPP they use an XSLT, and to build the PDF they use SBML2Latex. There are also SVG, GIF and various other visualizations available. There is also a link to the JWS online simulator.

They also have a Model of the Month, which is available via the web site or via an RSS feed. THey use AJAX for parts of their web interface: to view a models tree that is created based on the GO hierarchy; an internal-only annotation tool; sub-model generation and more. There is also a nice display of the Mathematical equations. They have a set of web services that are publicly accessible. The source code and database schema are available from sourceforge.

BioModels stores the frozen models: the way the models were when the publications were submitted. They need to correspond exactly to how it was published. However, if a modification was created by the authors and then a new paper made, the new version can then go into the database. If the models don't run, they don't reproduce the published results and therefore aren't MIRIAM compliant. Therefore they remain in the non-curated section of the database.

SBML Converters: Nicolas Rodriguez

They have: Scilab, XPP, CellML 1.0, BioPax Level 2, Dot/SVG, Vcell and PDF. For BioPax the original conversion lost a lot of granularity (physical entity -> species, for example). Now, by making use of the MIRIAM annotation, a more precise characterization can be made (e.g. UniProt annotation implies a protein in biopax, which is more specific than physical entity). For CellML, a new conversion from SBML to CellML is being developed by Andrew Miller, but it is still in the early stages. They're waiting for CellML 1.2 + CellML metadata to make the conversion better. The current SVG and GIF exports are not satisfactory, and they're looking for collaboration with other groups or efforts.

Model Curation and Annotation: Lukas Endler

Within the curated branch, models are: checked for MIRIAM compliance, a curation figure is added, model elements are manually added, and they get a BioModels ID. In the non-curated branch they are only slightly edited by curators, and only publication details and creation details are added. For MIRIAM compliance specifically within BioModels (more restrictive than MIRIAM compliance), the models must be: correctly encoded in a standard format (valid SBML), contain a link to a peer-reviewed journal, the creators' contact details, be able to reproduce the results given in the reference publication, and reflect the structure of the processes and formulas described in the reference publication.

The non-curated branch is valid SBML, but not MIRIAM compliant: cannot reproduce results, the models differ in structure from the publication, or it is not a kinetic model. If it is MIRIAM compliant, then it goes into this branch if the models contain kinetics they do not know how to curate yet (boolean models) or some parts are not encoded in SBML (e.g. spatial information). Another reason it would go here if it is MIRIAM compliant is if there is a significant tailback due to insufficient time and workforce, in which case it will be moved into the curated branch as soon as possible.

The curation guidelines are that they should: read the publication; go through the SBML model and compare all the elements (where possible they create reactions out of differential equations, add names to unnamed reactions, rules and events); change names and IDs to correspond to the article; try to reproduce one or two key results of the reference publication and create a curation result (e.g. a figure or table); add notes; move the model to the curated branch for annotation and publication.

http://biomodels.net/meetings/2008/index.html (Yes, it is the 2009 meeting, even though the URL says "2008").

Please note that this post is merely my notes on the presentation. They are not guaranteed to be correct, and unless explicitly stated are not my opinions. They do not reflect the opinions of my employers. Any errors you can happily assume to be mine and no-one else's. I'm happy to correct any errors you may spot – just let me know!

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