Registry of Standard Biological Models/BioSysBio Abstract Draft

Registry of BioBricks Models using CellML

Author(s): Vincent Rouilly¹, Barry Canton², Poul Nielsen³, Richard Kitney¹
Affiliations: ¹Imperial College London, ²MIT, ³The University of Auckland
Contact:email: vincent.rouilly@ic.ac.uk
Keywords: 'synthetic biology' 'biobrick' 'cellML' 'model database'

Introduction

One of the main goal in Synthetic Biology is to assess the possibility of building biological systems from interchangeable and standardized parts. In order to provide building blocks, a Registry of standardized DNA BioBricks has been established at the MIT. BioBricks can then be assembled to form devices or more complicated systems in living cells.

As in most engineering fields, the challenge begins with a comprehensive description and understanding of the problem. This involves qualitative and quantitative analysis: clear physical interpretation of the problem followed by an adequate mathematical description.

Therefore, alongside the effort of extending the number of parts available and characterizing them experimentally , a logical extension to the Registry would be to build a Registry of Biobrick Models to complement the wetlab work.

Motivations behind a Registry of BioBrick Models

to store, search and curate models related to physical DNA Biobricks. to gain a deeper understanding in the way BioBricks work. to promote the re-useability of BioBrick models. to explore through simulations the properties of de-novo assemblies between parts. to go towards a faster/cheaper development process. to complement the open-source spirit in Synthetic Biology and open-up a new form of "dry-work" contributions.

A key aspect in this effort is the use of a description language being able to describe and support the BioBrick concepts.

Properties needed for BioBrick description language
	Human and machine readable. Enable the description of qualitative and quantitative models of biochemical networks. Enable the definition of modules (as biobricks have inputs/outputs). Enable the definition of hierarchies between modules (as a system will be composed of sub-systems or devices). Enable a annotation scheme to comply with MIRIAM, for example.

Results

In this article, is demonstrated that such Registry of BioBrick Models is achievable. A mock-up is provided based on the great flexibility and modularity offered by CellML.

Following the steps of already succesfull model registries such as SBML registry, CellML registry or BioModel registry, a BioBrick Model Registry will enable the curation of models. Using CellML and a MIRIAM annotation scheme will guaranty compliance with the previously cited registries. However, a strong emphasis is made on coupling the DNA BioBrick characterisation with their corresponding models. An iterative process between qualitative modelling and experimental characterization will insure consistency. The proposed framework could be the base of a future CAD environment for Synthetic Biology.

Generic CellML architecture for BioBricks
Activated Promoter/RBS Brick Architecture	First, we explore the definition of modular and re-useable models to represent the available DNA BioBricks. A series of generic model architectures in CellML is defined for most of the types of parts encountered in the DNA registry (plasmid, promoter, RBS, proteins, riboswitch ...).
Catalog of quantitative BioBrick models
BioBrick Model Catalog	Second, a catalog of quantitative models based on already characterized parts is presented. An ongoing effort to characterized experimentaly BioBricks is providing us data to move from a qualitative description to a more quantitative one.
Building simulations from modular BioBrick models
Inverter Brick Architecture	To conclude, the versatility of the approach is demonstrated by simulating different sytems from a set of pre-defined models: Elowitz's Repressilator. Band Detector from Basu and Weiss.

Conclusion

The concept of a Registry of BioBrick models based on CellML has been demonstrated. It takes advantage of CellML flexibility and modularity to provide a catalog of quantitative models which are standardized, modular and re-useable. With the increase of available physical DNA parts in the MIT Registry, as well as the characterization of these parts, such a repository will help to gain a deeper understanding of the BioBrick properties and speeding up the process of building-up new devices and systems. But more importantly, it will help to federate the growing number of contributions from the modeling community.

Stuff that we might want to include too

• synergy between the definition of a biobrick model and the way its characterization is done (validation scheme between simulation and experiment)
• future work: CAD system with drag and drop of biobricks and use of 'CellML units' to validate connections between modules,
• elaborate on MIRIAM compliance + touch on linking model with gene and protein databases.
• conclusion is not great ...

References

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