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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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Thank you!

bcanton@mit.eduvincent.rouilly@gmail.com

http://openwetware.org/wiki/RoSBM

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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