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Expanding Horizons to Include More Modelling Approaches and Formats Mihai Glont1, Tung V D1248–D1253 Nucleic Acids Research, 2018, Vol. 46, Database issue Published online 2 November 2017 doi: 10.1093/nar/gkx1023 BioModels: expanding horizons to include more modelling approaches and formats Mihai Glont1, Tung V. N. Nguyen1, Martin Graesslin2, Robert Halke¨ 3,RazaAli1, Jochen Schramm2, Sarala M. Wimalaratne1, Varun B. Kothamachu1,4, Nicolas Rodriguez4, Maciej J. Swat1, Jurgen Eils2, Roland Eils2, Camille Laibe1, Rahuman S. Malik-Sheriff1,*, Vijayalakshmi Chelliah1, Nicolas Le Novere` 4,* and Henning Hermjakob1,* 1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK, 2Department of Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, University of Heidelberg, BioQuant, IPMB and DKFZ Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany, 3University of Rostock, Rostock, Germany and 4Babraham Institute, Cambridge CB22 3AT, UK Received September 25, 2017; Editorial Decision October 17, 2017; Accepted October 18, 2017 ABSTRACT a resource that facilitates the exchange, reuse and repurpos- ing of the models. Since its inception, BioModels’ content BioModels serves as a central repository of mathe- has been steadily increasing, making it a central portal that matical models representing biological processes. It provides reproducible, high-quality, freely accessible mod- offers a platform to make mathematical models easily els published in the scientific literature. BioModels hosts shareable across the systems modelling community, over 8400 models from the scientific literature submitted thereby supporting model reuse. To facilitate host- by authors as well as internal and external BioModels cu- ing a broader range of model formats derived from rators. This includes a recent submission of 6750 patient- diverse modelling approaches and tools, a new in- specific genome-scale metabolic models derived from tu- frastructure for BioModels has been developed that mour samples of individual patients (2). Where possible, is available at http://www.ebi.ac.uk/biomodels. This models submitted to BioModels are manually curated to re- new system allows submitting and sharing of a wide produce the simulation figures in the reference publication and are semantically enriched using cross references to ex- range of models with improved support for formats ternal database resources and ontologies. BioModels also other than SBML. It also offers a version-control hosts over 140 000 models generated from biological path- backed environment in which authors and curators ways produced by the Path2Models project (3). All hosted can work collaboratively to curate models. This arti- models are freely available to access and download through cle summarises the features available in the current BioModels, either individually from our website (http:// system and discusses the potential benefit they of- www.ebi.ac.uk/biomodels) or as release archives from our fer to the users over the previous system. In sum- FTP server (ftp://ftp.ebi.ac.uk/pub/databases/biomodels/), mary, the new portal broadens the scope of mod- under Creative Commons (CC0) licence. Thereby BioMod- els accepted in BioModels and supports collabora- els allows modellers to submit and share their models with tive model curation which is crucial for model repro- the broader scientific community. ducibility and sharing. Mathematical modelling of biological systems has be- come increasing popular over past five decades and di- verse modelling approaches have evolved over this pe- riod. To cater for the growing need to host models of INTRODUCTION different approaches and formats, a new infrastructure Mathematical models representing biological processes and has been developed and made available at www.ebi.ac.uk/ computational simulations have been shown to provide biomodels. The new application is based on JUst a Model mechanistic insight into the functional properties of bio- Management Platform (JUMMP) (https://bitbucket.org/ logical systems. BioModels (1) emerged in 2005 as a re- jummp/jummp), a free, open source, solution for managing sponse to the needs of the systems biology community for *To whom correspondence should be addressed. Tel: +44 1223 494 418; Fax: +44 1223 484 696; Email: [email protected] Correspondence may also be addressed to Nicolas Le Novere.` Tel: +44 1223 496433; Email: [email protected] Correspondence may also be addressed to Henning Hermjakob. Tel: +44 1223 494 671; Fax: +44 1223 48 46 96; Email: [email protected] C The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Downloaded from https://academic.oup.com/nar/article-abstract/46/D1/D1248/4584626 by guest on 23 January 2018 Nucleic Acids Research, 2018, Vol. 46, Database issue D1249 fier that can be used as a means of referencing the modelin publications as well as retrieving it. COLLABORATIVE CURATION To ensure reproducibility and facilitate reuse, models sub- mitted to BioModels are curated and annotated by the cu- ration team, often with help from the authors. Models are independently verified to reproduce the simulation results Figure 1. Shows some of the modelling approaches and formats that in the reference publication. Furthermore, to unambigu- BioModels supports with its current JUMMP-based infrastructure. In ad- dition to model files, the current platform also allows the submission of ously identify model entities, they are linked to publicly other supporting model related files. available external resources used in Life Sciences such as online databases, controlled vocabularies or ontologies by means of identifiers.org (9) Uniform Resource Identifiers. mathematical models. One of the landmark improvements Although manual curation and semantic enrichment make brought by this upgrade is the provision of a flexible plat- a model more suitable for dissemination, reuse and repur- form that allows submitting and hosting of models in di- posing, these processes are laborious and time consuming. verse encoding formats. Unlike our previous platform that The new system provides several features for streamlining primarily supports SBML (4) and CellML (5), the current them. one can support models built using different modelling ap- In the previous infrastructure, submitted model files proaches and softwares. Additional features include a pow- could only be updated by curators at the request of authors. erful faceted search engine and enhanced provision for col- The current version allows authors to perform a range of laborative curation. actions on the models from submission to curation. MULTIFORMAT MODEL SUBMISSION Updating models BioModels aims to make open-access sharing of high- Users may add, modify or remove files associated with a quality physiologically and pharmaceutically relevant mod- submission, or update the publication details and annota- els from scientific literature easy. Its endorsement for com- tions as necessary. The changes are organised as a series of munity standards used to encode models and associated incremental snapshots or revisions of the model that are metadata, combined with its curation efforts have estab- immutable. Previous revisions can be accessed and down- lished it as one of the most widely used repositories of its loaded even after newer changes have been introduced. This kind (6). The combination of these factors facilitates the ex- development history workflow is similar to flexible version change, reuse and repurposing of the models hosted therein. control systems like Git (http://www.git-scm.com) or Sub- Key parts of the functionality in the previous system (1), version (https://subversion.apache.org), but without the as- including the curation pipeline and the model display page, sociated technical proficiency requirements. are contingent on the model being encoded in standard for- mats including SBML or CellML. For submissions in other Managing model access rights formats curators resort to creating a skeletal SBML repre- sentation that references the original model. The new infras- Model development is inherently a collaborative effort, tructure removes this technical hindrance, allowing authors bringing together people with different backgrounds and to submit models encoded in the format of their choice in- even from different organisations. Often models undergo cluding Python, Mathematica or Matlab SimBiology, and several refinements before being fit for purpose. In recogni- regardless of the modelling approach employed (Figure 1). tion of this, model revisions in the new version of the service To foster interoperability and model reuse, the new system are private by default. Submitters can share a model with offers enhanced technical support for open formats such individual users or with teams of collaborators, choosing to as SBML, PharmML (7) or COMBINE Archive (8). This grant them read-write or read-only access (Figure 2). Spe- expansion of scope for submissions offers more modelling cific revisions can be made publicly available by a BioMod- communities the ability to leverage BioModels for dissemi- els curator once they meet the required criteria (Figure 3). nation, exchange and reuse of the models that they develop. Once submitted,
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