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The chapter reviews the syntax to store machine-readable annotations and describes the mapping between rule-based modelling entities (e.g., agents and rules) and these annotations. In particular, we review an annotation framework and the associated guidelines for annotating rule-based models, encoded in the commonly used Kappa and BioNetGen languages, and present prototypes that can be used to extract and query the annotations. An ontology is used to annotate models and facilitate their description.

Motivation: 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., Results: 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., Availability and Implementation: 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, Contact: anil.wipat@newcastle.ac.uk or vdanos@inf.ed.ac.uk., (© The Author 2015. Published by Oxford University Press.)

Rule-based modeling, an alternative to traditional reaction-based modeling, allows us to intuitively specify biological interactions while abstracting from the underlying combinatorial complexity. One such rule-based modeling formalism is Kappa, which we introduce to readers in this chapter. We discuss the application of Kappa to three modeling scenarios in synthetic biology: a unidirectional switch based on nitrosylase induction in Saccharomyces cerevisiae, the repressilator in Escherichia coli formed from BioBrick parts, and a light-mediated extension to said repressilator developed by the University of Edinburgh team during iGEM 2010. The second and third scenarios in particular form a case-based introduction to the Kappa BioBrick Framework, allowing us to systematically address the modeling of devices and circuits based on BioBrick parts in Kappa. Through the use of these examples, we highlight the ease with which Kappa can model biological interactions both at the genetic and the protein-protein interaction level, resulting in detailed stochastic models accounting naturally for transcriptional and translational resource usage. We also hope to impart the intuitively modular nature of the modeling processes involved, supported by the introduction of visual representations of Kappa models. Concluding, we explore future endeavors aimed at making modeling of synthetic biology more user-friendly and accessible, taking advantage of the strengths of rule-based modeling in Kappa.