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: [email protected] or [email protected].

Populations of bacteria acting in collaboration can produce complex behaviors which are not achievable by individual cells. There has, consequently, been considerable interest in the engineering of bacterial populations. Here we describe an approach for the engineering of aspects of bacterial quorum communication, using Standard Virtual Parts, a synthetic biology programming language, dubbed SVPWrite, and an evolutionary algorithm. We apply this system to engineering the output characteristics of the subtilin receiver system of Bacillus subtilis. Simple modifications, such as altering the strength of the output response to a subtilin input, are easily achieved. More complex adaptations, such as modifying the shape of the receiver response curve, necessitate alterations to the topology of the regulatory network. More generally, the use of Standard Virtual Parts and a programming language allow circuit design, simulation and evaluation to easily be automated, permitting exploration of a far larger proportion of design space than would be possible using standard manual design approaches.