Latest revision as of 01:34, 30 October 2008

Newcastle University

GOLD MEDAL WINNER 2008

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Home >> Modelling

Introduction to CellML

The programming language chosen for modelling was [http://www.cellml.org/ CellML]. CellML has been used extensively to model human physiology as part of the [http://www.physiome.org.nz/ Physiome] project, but is equally suitable for modelling biological pathways and the molecules involved in these. CellML models are based on a modular structure, which is appropriate when modelling the behaviour of biological parts. CellML seeks to model the mathematics behind biological systems. This is beneficial when capturing information but the implications are that the mathematics behind the behaviour must be clearly defined and understood.

CellML is good at describing biological entities in a modular fashion and can also express a wide range of different kinds of model. The modularity of CellML is important for this BugBuster project as it enables models of separate components to be built separately and then later be combined into a single, integrated model. This was used to explore possible genetic networks by combining models from the parts and constraints repositories.

CellML integrates the language MathML to describe the mathematical relationships between different components and variables within a biological model(Lloyd, et al., 2004). Every variable must have physically defined units. This makes the language more explicit and consistent, eliminates a large range of errors. The ultimate aim for the CellML language is for the research community to build models and make them freely available for others to build on(Lloyd, et al., 2004). We have used the CellML language in defining all of our part and constraint models.

Model generation and simulation

Modelling in the CellML language was carried out in the [http://cor.physiol.ox.ac.uk/ Cellular Open Resource (COR)] (Garny, et al., 2003). COR is a free resource available in Microsoft Windows. This provides an editor to write in COR language, which was more easy for human editing than the XML-based mark-up language. The text is converted into the CELLML XML format by the program, which complies and runs models as they are created. Once models were generated in COR, they were loaded into [http://www.cellml.org/tools/pcenv/ PCEnv] for simulation.

Modelling of our proof of concept subtilin quorum peptide receiver

Our subtilin receiver model was assembled from invidual virtual part models, together with the compartment

An overview of the CellML compartments and their interconnections for the subtilin receiver model.

Download a high resolution version of this image File:ProofOfConceptModelOverview.zip

Simulations of the subtilin receiver CellML model using COR:

Accumulation of activated (phosphorylated) SpaR in the presence of 20 um subtilin

Accumulation of activated (phosphorylated) SpaR in the presence of 50 um subtilin

Downloads

File:Newcastle-igem2008-CellML-models.zip	Contains the CellML models created as part of the Parts Repository. See Team:Newcastle University/Parts Repository for more information.
File:Newcastle-igem2008-CellML-components.zip	Contains the individual component text files, containing CellML, from the Parts Repository. See Team:Newcastle University/Parts Repository for more information.
File:Subtilin receiver.zip	Contains: The CellML model of the proof of concept BioBrick, subtilin receiver as shown above. See Proof of Concept Brick for more information.

@@ Line 4: / Line 4: @@
 ==Introduction to CellML==
-The programming language chosen for modelling was [http://www.cellml.org/ CellML]. CellML has mainly been used to model biological pathways and the molecules involved in these (CellML model repository, 2008).  CellML models are based on a modular structure, which is appropriate when modelling the behaviour of biological parts (Rouilly, et al., 2007).  CellML is accepted as a standard by members of the Physiome project (The Physiome Project, 2006).
+The programming language chosen for modelling was [http://www.cellml.org/ CellML]. CellML has been used extensively to model human physiology as part of the [http://www.physiome.org.nz/ Physiome] project, but is equally suitable for modelling biological pathways and the molecules involved in these.  CellML models are based on a modular structure, which is appropriate when modelling the behaviour of biological parts.  CellML seeks to model the mathematics behind biological systems.  This is beneficial when capturing information but the implications are that the mathematics behind the behaviour must be clearly defined and understood.
+CellML is good at describing biological entities in a modular fashion and can also express a wide range of different kinds of model.  The modularity of CellML is important for this BugBuster project as it enables models of separate components to be built separately and then later be combined into a single, integrated model. This was used to explore possible genetic networks by combining  models from the parts and constraints repositories.
+CellML integrates the language MathML to describe the mathematical relationships between different components and variables within a biological model(Lloyd, et al., 2004).  Every variable must have physically defined units.  This makes the language more explicit and consistent, eliminates a large range of errors.  The ultimate aim for the CellML language is for the research community to build models and make them freely available for others to build on(Lloyd, et al., 2004).  We have used the CellML language in defining all of our part and constraint models.
-CellML looks to model the mathematics behind this system (Schilstra, et al., 2006).  This is beneficial when capturing information but the implications are that the mathematics behind the behaviour must be clearly defined and understood. An aim of CellML was to overcome some of the limitations of SBML (Lloyd, et al., 2004). Particularly, the modularity of CellML allows it to be utilised on a large scale.  Whole models or components of parts of models can be integrated successfully to produce larger models whilst maintaining the language structure (Lloyd, et al., 2004).
 ==Model generation and simulation==
-Modelling in the CellML language was carried out in the [http://cor.physiol.ox.ac.uk/ Cellular Open Resource (COR)] (Garny, et al., 2003).  COR is a free resource available in Microsoft Windows.  This provides an editor to write in COR language, which has easier readability than the mark-up language. The text is converted into CELLML by the program, which complies and runs models as they are created. Once models were generated in COR, they were loaded into [http://www.cellml.org/tools/pcenv/ PCEnv] for simulation.
+Modelling in the CellML language was carried out in the [http://cor.physiol.ox.ac.uk/ Cellular Open Resource (COR)] (Garny, et al., 2003).  COR is a free resource available in Microsoft Windows.  This provides an editor to write in COR language, which was more easy for human editing than the XML-based mark-up language. The text is converted into the CELLML XML format by the program, which complies and runs models as they are created. Once models were generated in COR, they were loaded into [http://www.cellml.org/tools/pcenv/ PCEnv] for simulation.
+==Modelling of our proof of concept subtilin quorum peptide receiver==
+Our subtilin receiver model was assembled from invidual virtual part models, together with the compartment
+An overview of the CellML compartments and their interconnections for the subtilin receiver model.
+[[Image:Model3.001.png|thumb|centre]]
+Download a high resolution version of this image [[Image:ProofOfConceptModelOverview.zip]]
+----
+==Simulations of the subtilin receiver CellML model using COR:==
+===Accumulation of activated (phosphorylated) SpaR in the presence of 20 um subtilin===
+[[Image:20mM Subtilin actSpaR.png]]
+===Accumulation of activated (phosphorylated) SpaR in the presence of 50 um subtilin===
+[[Image:50mM Subtilin actSpaR.png]]
+----
 ==Downloads==
-Download:
+<table border="1"><tr><td valign="top">
-[[Image:Newcastle-igem2008-CellML-models.zip]] contains:
+[[Image:Newcastle-igem2008-CellML-models.zip]]
-* Alt.promoter.constitutive.cellml
+<td valign="top">
-* Alt.promoter.constitutiveImport.cellml
+Contains the CellML models created as part of the Parts Repository. See [[Team:Newcastle University/Parts Repository]] for more information.
-* Alt.promoter.inductive.cellml
+<tr><td valign="top">
-* Alt.promoter.inductive3.cellml
+[[Image:Newcastle-igem2008-CellML-components.zip]]
-* Alt.promoter.respressive.cellml
+<td valign="top">
-* Alt.protein.cellml
+Contains the individual component text files, containing CellML, from the Parts Repository. See [[Team:Newcastle University/Parts Repository]] for more information.
-* Alt.RBS.cellml
+<tr><td valign="top">
-* Bacillus RBS.cellml
+[[Image:Subtilin receiver.zip]]
-* Basic promoter 2.cellml
+</td><td valign="top">
-* Basic promoter 3.cellml
+Contains: The CellML model of the proof of concept BioBrick, subtilin receiver as shown above. See [[Team:Newcastle University/ProofOfConceptBrick|Proof of Concept Brick]] for more information.
-* Basic Promoter.cellml
+<html></td></tr></table></html>
-* Check comp.cellml
-* CodingRegion.cellml
+===Further Reading===
-* ComD(NoInducSynthWithComEP).cellml
+Garny, A. (2003) Cellular Open Resource(COR): A public CellML based environment for modelling biological function, ''International Journal of Bifurcation and Chaos'', '''13''', 3579-3590.
-* ComD.cellml
-* ComDAGAIN.cellml
-* composite2.cellml
-* CompositeModel.cellml
-* constitutive promoter.cellml
-* DNAa.cellml
-* EncodedProtein.cellml
-* example tut3main.cellml
-* example tut3sub..cellml
-* FluxComEP.cellml
-* ftsA.cellml
-* ftsW.cellml
-* HySpank.cellml
-* InitialRBS.cellml
-* minC.cellml
-* NewComD.cellml
-* PbofA.cellml
-* PcotA.cellml
-* Protein.cellml
-* proteinCoding.cellml
-* PspaS.cellml
-* PspollQ.cellml
-* Pxyl.cellml
-* ResponseRegulator.cellml
-* Sensor.cellml
-* Tanscription factor.cellml
-* To join the components together.doc
-* veg.cellml
-* XComDP.cellml
-* zapA.cellml
-[[Image:Newcastle-igem2008-CellML-components.zip]] contains:
+Lloyd, C.M., Halstead, M.D.B. and Nielsen, P.F. (2004) CellML: its future, present and past, ''Progress in Biophysics & Molecular Biology'', '''85''', 433-450.
-* AgrA.txt
-* AgrC.txt
-* Bind Components.txt
-* CFP.txt
-* Cin-box.txt
-* ComD.txt
-* ComE.txt
-* ConstitutivePromoter.txt
-* DNAa.txt
-* Environment.txt
-* Essentials.txt
-* Footer.txt
-* ftsA.txt
-* ftsW.txt
-* GFP.txt
-* Header.txt
-* HySpank.txt
-* InducablePromoter.txt
-* mCherry.txt
-* minC.txt
-* OptimalRBS.txt
-* P2.txt
-* P3.txt
-* PbofA.txt
-* PbofAmod.txt
-* PcotA.txt
-* PlcA.txt
-* PromoterToRBS.txt
-* Protein.txt
-* PspaS.txt
-* PspollQ.txt
-* Pxyl.txt
-* RBS.txt
-* RBSToCodingRegion.txt
-* RepressablePromoter.txt
-* ResponseRegulator.txt
-* Sensor.txt
-* Units.txt
-* veg.txt
-* XyloseIsomerase.txt
-* YFP.txt
-* YocF.txt
-* YocG.txt
-* zapA.txt

Team:Newcastle University/Modelling

From 2008.igem.org