Registry of Standard Biological Models/CellML Practical

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23 April 2024

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22 April 2024

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21 April 2024

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18 April 2024

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Scope of the abstract

• Demonstrate the use of CellML 1.1 to describe BioBricks [1](encapsulated and hierarchical assemblies)
  • building a modular Repressilator (see practicals)
• Define requested features of a Virtual BioBrick Repository
  • review on existing model repository
  • specific requirements for a virtual biobrick repository
  • toward a Synthetic Biology CAD system

Practical with CellML to describe BioBricks

CellML 1.1 looks very flexible and could provide all the desired features that we are looking for in order to describe a BioBrick [2]. Some testing has to be done on real examples to see how far we can incorporate BioBrick concepts into CellML description capabilities.

• Practical 1: Describe a simple genetic assembly (promoter + RBS + protein coding region + stop codon) from the description of each sub-component.
  • example of such a part: <bbpart>BBa_I13522</bbpart>
    • It might be better to use <bbpart>BBa_I7101</bbpart> as this has been characterized quite extensively by Caitlin Conboy and Jennifer Braff (westerns, northerns etc.).
  • the concept of PoPS [3] could be used as a connection mechanism from a dynamical perspective
  • Each part could be represented as a CellML 'component' and then a group could be created to produce the final assembly

• Practical 2: Describe a standardized inverter as a CellML module (example found here <bbpart>BBa_Q04121</bbpart> )
  • NB: this is a non functional assembly as there is no promoter to the coding region
  • Define clear inputs and outputs to allow future assembly with counter parts (i.e. LacI protein with LacI promoter)

• Practical 3: From 3 standardized inverter build the Elowitz repressilator
  • part found here: <bbpart>BBa_I5610</bbpart>
  • demonstrate modularity and re-use offered by CellML
  • An abstraction could be created to encapsulate everything and define an oscillator device (use of group concept in CellML).

General aim

In this article, we are investigating the creation of a virtual equivalent to the DNA parts registry using CellML. Each physical DNA part would have one or multiple models to describe their properties. A model registry could be the core of a CAD system for synthetic biology where new assemblies of parts would be simulated and tested before starting the wetlab.

This problem has 2 main required features: a standardized description language and a structured repository for the created models

• Wish list for a BioBrick description language
  • standardized
  • machine and human readable
  • quantitative and/or qualitative description
  • modular
  • hierarchical

Wish list for a BioBrick model repository

• • store, curate and search models
  • reference DNA part registry
  • drag and drop mechanism to assemble new systems

Background and References

• Description language for bio-models
  • CellML [4]
  • SBML [5]
  • MML

• Databases of models
  • CellML repository [6]
  • BioModels [www.ebi.ac.uk/biomodels]

• Previous CAD system
  • BioJADE [7]
  • BioSPICE [8]

• BioBricks [9]
• Part registry[10]