Practical steps to digital organism models, from laboratory model species to 'Crops in silico.

A recent initiative named 'Crops in silico' proposes that multi-scale models 'have the potential to fill in missing mechanistic details and generate new hypotheses to prioritize directed engineering efforts' in plant science, particularly directed to crop species. To that end, the group called for 'a paradigm shift in plant modelling, from largely isolated efforts to a connected community'. 'Wet' (experimental) research has been especially productive in plant science, since the adoption of Arabidopsis thaliana as a laboratory model species allowed the emergence of an Arabidopsis research community. Parts of this community invested in 'dry' (theoretical) research, under the rubric of Systems Biology. Our past research combined concepts from Systems Biology and crop modelling. Here we outline the approaches that seem most relevant to connected, 'digital organism' initiatives. We illustrate the scale of experimental research required, by collecting the kinetic parameter values that are required for a quantitative, dynamic model of a gene regulatory network. By comparison with the Systems Biology Markup Language (SBML) community, we note computational resources and community structures that will help to realize the potential for plant Systems Biology to connect with a broader crop science community.

A high-level language for rule-based modelling.

Rule-based languages such as Kappa excel in their support for handling the combinatorial complexities prevalent in many biological systems, including signalling pathways. But Kappa provides little structure for organising rules, and large models can therefore be hard to read and maintain. This paper introduces a high-level, modular extension of Kappa called LBS-κ. We demonstrate the constructs of the language through examples and three case studies: a chemotaxis switch ring, a MAPK cascade, and an insulin signalling pathway. We then provide a formal definition of LBS-κ through an abstract syntax and a translation to plain Kappa. The translation is implemented in a compiler tool which is available as a web application. We finally demonstrate how to increase the expressivity of LBS-κ through embedded scripts in a general-purpose programming language, a technique which we view as generally applicable to other domain specific languages.