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Registry of Standard Biological Models
Barry Canton (MIT)
Vincent Rouilly (Imperial College)
Registry Workshop
November 2007,Boston
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Biological Systems Need Models!
Michigan iGEM Team ‘07
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Challenges
• Modeling takes time, expertize
• Weak adoption of standards for model construction
• Models hard to share, reuse
(Sound familiar?)
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Challenges
• Building takes time, expertize
• Weak adoption of standards for system construction
• Parts hard to share, reuse
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Registry of Standard Biological Parts
http://parts.mit.edu
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http://openwetare.org/wiki/RoSBM
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Wiki
Modeling & the Parts Registry
Project 1
-models-
Project 2
-models-
Project 3
-models-
Project 4
-models-
Project 5
-models-
Parts
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Wiki
Modeling with Parts & Models Registries
Project 1
-models-
Project 2
-models-
Project 3
-models-
Project 4
-models-
Project 5
-models-
Parts Models
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Wiki
Open data sharing
Project 1
-models-
Project 2
-models-
Project 3
-models-
Project 4
-models-
Project 5
-models-
Model Predictions
Experimental Data
Parts Models
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CellML Database
http://www.cellml.org/models
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Biomodels Database
http://www.ebi.ac.uk/biomodels/
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Asmparts software
http://soft.synth-bio.org/asmparts.html
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MIRIAM initiative
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RoSBM Motivations / Mission
• to gain a deeper understanding of the function of BioBricks.• to promote the re-usability of BioBrick models.• to explore through simulations the properties of de-novo
assemblies of parts.• to progress towards a faster/cheaper development process.• to complement the open-source spirit of Synthetic Biology
and open-up a new form of in Silico contributions.
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What Do We Want the RoSBM to Do?
• Store, Search, Annotate, and Curate models of standardized biological parts.
• Provide a one-to-many match between DNA biological parts and models.
• Interface with CAD tools.
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BioBrick Characterization
€
SynthesisRate =nbGenes• Smax • [AHL]
n
Kmn + [AHL]n
nbGenes = plasmid number
Smax =max transcription rate
n = Hill Coefficient
Km = Sensitivity
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BioBrick Characterization
€
SynthesisRate =nbGenes• Smax • [AHL]
n
Kmn + [AHL]n
nbGenes = plasmid number
Smax =max transcription rate
n = Hill Coefficient
Km = Sensitivity
Smax=XXXN=1.2
Experiments Modeling
Early experiments to estimate dynamic range of AHL and general response
More experiments to improve estimationOf parameters
Define Model
Fit Model on Data
Predict next best experimental points
Fit model on new data
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GFP(t) = f(AHL,LuxR,t)
One part, many models?
BBa_T9002
GFP = f(AHL)
GFP(t) = f(AHL,mRNALuxR, PLuxR, mRNAGFP, PLuxR, RNAp,
Ribosomes, t)
Parts Models
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Proof of Concept
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desired relationships
ModelPart SimilarModels
ModelsIncludingThis one
ModelsIncluded in
this one
BioDB
Partcategory
Modelcategory
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Data Connectivity
Parts Models
Exp.Data
Sim.Data
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Data Connectivity
Parts Models
Exp.Data
Sim.Data
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Data Connectivity
Parts Models
Exp.Data
Sim.Data
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Data Connectivity
Parts Models
Exp.Data
Sim.Data
PartsParts
Exp.Data
ModelsModelsModelsModelsModels
Sim.DataSim.Data
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ideas
• Level of abstraction
• controlled vocabularies
• Description language
• MIAGE standard
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Model Curation
• Machine readable
• Conform to a description standard
• Make sure the model works
• Referencing author, publications, contact
• Pointing to biological databases
• MIRIAM standard
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SBML / CellML Overview
SBMLmodel =
CellMLmodel =
CompartmentsSpeciesRules
ReactionsEvents
ComponentsVariables: name, init_value, interface, units
MathUnits
Imports
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What is a Biological Part Model?
• What we mean by Biological Model:– Abstraction of a biological process using a
formal mathematical description– Focus on kinetic models– Focus on Ordinary Differential Equations
System
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Content
• Advantages offered by modelling• Problems to be addressed• A solution to some of the above (Motivations)• An example of a model entry in the RoSBM
(Scenarii of use)• What is a ‘Standard Biological Model’ ?• Simple Model repository or reusable modeling
component. • Open issues (level of abstraction, description
language, …)
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Current Practices
• More and more projects explore their project with modelling
• Matlab, C/C++, Proprietary platform, SBML
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Unused Images