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Published December 10, 2013 | Supplemental Material + Published + Submitted
Journal Article Open

SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools


Background: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing. Results: We present the Systems Biology Markup Language (SBML) Qualitative Models Package ("qual"), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models. Conclusions: SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks.

Additional Information

© 2013 Chaouiya et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 15 August 2013 Accepted: 26 November 2013. Published: 10 December 2013. Authors thank the members of the SBML qual mailing list for their contributions and/or feedback during the development of the qual package specification. We also thank Aidan MacNamara and Federica Eduati for help with the EGF/TNFα model. Furthermore, we appreciate financial aids from the European Union through the "BioPreDyn" project to JSR (ECFP7-KBBE-2011-5 Grant #289434), Nebraska NASA Space Grant Consortium grant ("Technology for collaborative biomedical research") and National Institutes of Health grant support (#5R01DA030962) to TH, Fundação para a Ciência e a Tecnologia (grant PTDC/EIA-CCO/099229/2008) to CC, US National Institute of General Medical Sciences support (#GM070923) for SMK, MH and NLN, a Marie Curie International Outgoing Fellowship within the EU 7th Framework Program for Research and Technological Development (project AMBiCon, 332020) to AD, the Swiss Federal Government through the Federal Office of Education Science and Innovation (SERI) and the European Commission FP6 project ENFIN (Experimental Network for Functional INtegration – LSHGCT-2005-518254) to IX, the Fundação para a Ciência e a Tecnologia (grant Pest-OE/EEI/LA0021) to PTM, Federal Ministry of Education and Research (BMBF, Germany) as part of the Virtual Liver Network (grant number 0315756, 0315744) to AD, SK. FB, MvI, JSR and NLN also benefited from dedicated support by EMBL-EBI. Authors' contributions: CC, JSR, and TH designed the workflow and case studies presented here and wrote the manuscript. CC initiated, coordinated and contributed to the development of SBML qual. CC coordinated the support of the package in GINsim. JSR contributed to the development of SBML qual, and supervised its implementation in CellNOpt. TH contributed to the development of SBML qual, and coordinated the implementation of its support in the Cell Collective. NLN initiated the development of SBML qual, provided the initial version of the package and the support in libSBML, and contributed to the manuscript. DT initiated and regularly contributed to the development of SBML qual, and also contributed to the redaction of the manuscript. SMK contributed towards the finalisation of the SBML qual specification and developed the libSBML code that supports the format. DB contributed to the development of the qual package and developed a first support in LibSBML. AN contributed to the qual package, implemented its support in GINsim and implemented the LogicalModel library. MPI implemented an XML validator for SBML qual as part of LibSBML, helped review, collect feedback and improve the SBML qual specification, and created the first implementation of the CellNOpt-to-SBML-qual converter. AD and FB contributed to the development of SBML qual and to JSBML. JD implemented the SBML qual export in boolSim. IX contributed to the development of SBML qual. EG contributed to the support of SBML qual in CellNOpt and to the manuscript. PTM implemented the GINsim export to GNA, contributed to the GINsim support for SBML qual and to the manuscript. MP and HdJ tested the specification by developing SBML qual support for GNA; HdJ contributed to the manuscript. MH helped guide development of the SBML Level 3 "qual" package specification and contributed to the manuscript. SK contributed to SBML qual development and supervised its support in CellNetAnalyzer. AVK contributed to the requirements of the SBML package, and implementation of SBML support in CellNetAnalyzer. NR contributed to the development of SBML qual, and implemented support for the specification in JSBML. BK and BW implemented SBML qual support in the Cell Collective. TC participated in the case-study setting-up, simulations and import/export in CellNOpt, and contributed to the manuscript. All authors read and approved the final manuscript.

Attached Files

Published - 1752-0509-7-135.pdf

Submitted - 1309.1910.pdf

Supplemental Material - 12918_2013_1259_MOESM1_ESM.pdf


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