title: Annotation of rule-based models with formal semantics to enable creation, analysis, reuse and visualization.
abstract: Biological systems are complex and challenging to model and therefore model reuse is highly desirable. To promote model reuse, models should include both information about the specifics of simulations and the underlying biology in the form of metadata. The availability of computationally tractable metadata is especially important for the effective automated interpretation and processing of models. Metadata are typically represented as machine-readable annotations which enhance programmatic access to information about models. Rule-based languages have emerged as a modelling framework to represent the complexity of biological systems. Annotation approaches have been widely used for reaction-based formalisms such as SBML. However, rule-based languages still lack a rich annotation framework to add semantic information, such as machine-readable descriptions, to the components of a model.
  
  
  
  We present an annotation framework and guidelines for annotating rule-based models, encoded in the commonly used Kappa and BioNetGen languages. We adapt widely adopted annotation approaches to rule-based models. We initially propose a syntax to store machine-readable annotations and describe a mapping between rule-based modelling entities, such as agents and rules, and their annotations. We then describe an ontology to both annotate these models and capture the information contained therein, and demonstrate annotating these models using examples. Finally, we present a proof of concept tool for extracting annotations from a model that can be queried and analyzed in a uniform way. The uniform representation of the annotations can be used to facilitate the creation, analysis, reuse and visualization of rule-based models. Although examples are given, using specific implementations the proposed techniques can be applied to rule-based models in general.
  
  
  
  The annotation ontology for rule-based models can be found at http://purl.org/rbm/rbmo The krdf tool and associated executable examples are available at http://purl.org/rbm/rbmo/krdf
  
  
  
  anil.wipat@newcastle.ac.uk or vdanos@inf.ed.ac.uk.
authors.affiliation: Interdisciplinary Computing and Complex BioSystems Research Group, School of Computing Science and Centre for Synthetic Biology and the Bioeconomy, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Goksel
authors.initials: G
authors.lastname: Misirli
authors.affiliation: School of Informatics, University of Edinburgh, Edinburgh, UK and.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cavaliere
authors.affiliation: School of Informatics, University of Edinburgh, Edinburgh, UK and.
authors.forename: William
authors.initials: W
authors.lastname: Waites
authors.affiliation: Turing Ate My Hamster Ltd., Newcastle upon Tyne, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pocock
authors.affiliation: Interdisciplinary Computing and Complex BioSystems Research Group, School of Computing Science and Centre for Synthetic Biology and the Bioeconomy, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Curtis
authors.initials: C
authors.lastname: Madsen
authors.affiliation: Interdisciplinary Computing and Complex BioSystems Research Group, School of Computing Science and Centre for Synthetic Biology and the Bioeconomy, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Owen
authors.initials: O
authors.lastname: Gilfellon
authors.affiliation: School of Informatics, University of Edinburgh, Edinburgh, UK and.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Honorato-Zimmer
authors.affiliation: Interdisciplinary Computing and Complex BioSystems Research Group, School of Computing Science and Centre for Synthetic Biology and the Bioeconomy, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Zuliani
authors.affiliation: School of Informatics, University of Edinburgh, Edinburgh, UK and.
authors.forename: Vincent
authors.initials: V
authors.lastname: Danos
authors.affiliation: Interdisciplinary Computing and Complex BioSystems Research Group, School of Computing Science and Centre for Synthetic Biology and the Bioeconomy, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Anil
authors.initials: A
authors.lastname: Wipat
mesh_terms: D008962:Models, Theoretical; D012660:Semantics