The ERATO Systems Biology Workbench
Michael Hucka, Hamid Bolouri,
Andrew Finney, Herbert Sauro
ERATO Kitano Systems Biology Project
California Institute of Technology, Pasadena, CA, USA
Principal Investigators: John Doyle, Hiroaki Kitano
Collaborators: Adam Arkin (BioSpice), Dennis Bray (StochSim),
Igor Goryanin (DBsolve), Les Loew (Virtual Cell), Pedro Mendes
(Gepasi/Copasi), Masaru Tomita (E-Cell)
Background
• Modeling, simulation & analysis are critical
– Huge volumes of data
– Many disparate findings
• Rapid rate of software tool development
– Roles: data filtering, model creation, model simulation
– Many groups are creating many tools
• Different packages have different niche strengths
reflecting expertise & preferences of the group
• Strengths are often complementary to those of other
packages
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Complementary Strengths of Tools
Multistate reactions/stochastic
Reaction/Diffusion
Optimization
Bifurcation analysis
Visualization of networks
Handle large systems
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Problems
• No single package answers all needs of modelers
• No single tool is likely to do so in the near future
– Range of capabilities is large
– New techniques ( new tools) evolving too rapidly
• Researchers are likely to continue using multiple
packages for the foreseeable future
• Problems in using multiple tools:
– Simulations & results often cannot be shared or re-used
– Duplication of software development effort
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Goal & Approach
• Systems Biology Workbench goal: to provide
software infrastructure that
– Enables sharing of simulation/analysis software & models
– Enables collaboration between software developers
• Two-pronged approach:
– Develop a common model exchange language
• SBML: Systems Biology Markup Language
– Develop an environment that enables tools to interact
• SBW: Systems Biology Workbench
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Systems Biology Markup Language
• Problem:
– Many software tools, few common exchange formats
• Difficult to take advantage of multiple tools
• Difficult to establish repositories of models
• A Solution (In Principle):
– Define a common exchange language
• Use a simple, well-supported, textual substrate (XML)
• Add components that reflect the natural conceptual
constructs used by modelers in the domain
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Structure of Model Definitions in
SBML
• Domain: biochemical network models
• A model is described using a list of components:
– Beginning of model definition
» List of unit definitions (optional)
» List of compartments
» List of species
» List of parameters (optional)
» List of rules (optional)
» List of reactions
– End of model definition
• Each component has a specific structure
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Example
X0
k1*X0
k2*S1
X1
k3*S1
X2
S1
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Example (cont.)
<?xml version=“1.0” encoding=“UTF-8”?>
<sbml level=“1” version=“1”>
<model name=“simple”>
<listOfCompartments>
<compartment name=“c1” />
</listOfCompartments>
<listOfSpecies>
<specie name=“X0” compartment=“c1”
boundaryCondition=“true”
initialAmount=“1”/>
<specie name=“S1” compartment=“c1”
boundaryCondition=“false”
initialAmount=“0”/>
<specie name=“X1” compartment=“c1”
boundaryCondition=“true”
initialAmount=“0”/>
<specie name=“X2” compartment=“c1”
boundaryCondition=“true”
initialAmount=“0.23”/>
</listOfSpecies>
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Example (cont.)
<?xml version=“1.0” encoding=“UTF-8”?>
<sbml level=“1” version=“1”>
<model name=“simple”>
<listOfCompartments>
<compartment name=“c1” />
</listOfCompartments>
<listOfSpecies>
<specie name=“X0” compartment=“c1”
boundaryCondition=“true”
initialAmount=“1”/>
<specie name=“S1” compartment=“c1”
boundaryCondition=“false”
initialAmount=“0”/>
<specie name=“X1” compartment=“c1”
boundaryCondition=“true”
initialAmount=“0”/>
<specie name=“X2” compartment=“c1”
boundaryCondition=“true”
initialAmount=“0.23”/>
</listOfSpecies>
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Example (cont.)
<?xml version=“1.0” encoding=“UTF-8”?>
<sbml level=“1” version=“1”>
<model name=“simple”>
<listOfCompartments>
<compartment name=“c1” />
</listOfCompartments>
<listOfSpecies>
<specie name=“X0” compartment=“c1”
boundaryCondition=“true”
initialAmount=“1”/>
<specie name=“S1” compartment=“c1”
boundaryCondition=“false”
initialAmount=“0”/>
<specie name=“X1” compartment=“c1”
boundaryCondition=“true”
initialAmount=“0”/>
<specie name=“X2” compartment=“c1”
boundaryCondition=“true”
initialAmount=“0.23”/>
</listOfSpecies>
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Example (cont.)
<listOfReactions>
<reaction name=“reaction_1” reversible=“false”>
<listOfReactants>
<specieReference specie=“X0” stoichiometry=“1”/>
</listOfReactants>
<listOfProducts>
<specieReference specie=“X0” stoichiometry=“1”/>
</listOfProducs>
<kineticLaw formula=“k1 * X0”>
<listOfParameters>
<parameter name=“k1” value=“0”/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction name=“reaction_2” reversible=“false”>
<listOfReactants>
<specieReference specie=“S1” stoichiometry=“1”/>
</listOfReactants>
. . .
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Some Points About SBML
• Users do not write in XML — software tools do!
• SBML is being defined incrementally
– SBML Level 1 covers non-spatial biochemical models
• Intentionally kept simple for maximal compatibility
– SBML Level 2 will extend Level 1 with more facilities
Level 3?
Level 2
Level 1
E.g.: • Composition
• Geometry
• Arrays
… others
• Defined in abstract form (UML) + textual descriptions
– Used to define XML encoding + XML Schema
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Systems Biology Workbench
• Open-source, integrated software environment
that enables sharing of computational resources
– Allows software developers to build interprocess
communications facilities into their applications
• From the user’s perspective:
– One SBW-enabled application can interact with another
– Each application or module offers services to others
• E.g.: ODE solution, time-based simulation,
visualization, etc.
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From the User’s Perspective
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From the User’s Perspective
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From the User’s Perspective
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Behind the Scenes
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From the Programmer’s Perspective
• Desirable features
–
–
–
–
Small application programming interface (API)
Libraries that implement inter-program communications
A registry of services for applications to query
XML-based model representation (SBML)
• Uses well-known, proven technologies
– Communications via message-passing over plain sockets
– Modular, distributed, broker-based architecture
• API provides two styles:
– “Low-level”: call/send operations + directory services
– “High-level”: object-oriented interface layered on top
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Driving Principles
• Keep it language-neutral
– We’ll provide C++, Java, Delphi libraries for Win, Linux
• But can be implemented in any language
• Keep it simple
– Simple message-passing scheme
• Avoid complexity & size of CORBA
• Easy to make cross-platform compatible
• Easy to make distributed
– Simple low-level API, convenient higher-level API
• Make sure contributors benefit
– Open source development
– Symmetric infrastructure: no application dominates
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Modules Planned
• Data filtering & preparation
• Database support
– E.g.: web searching, storage management
• Model definition & manipulation
– E.g.: scripting languages, visual editors
• Equation solvers
– E.g.: ODEs, DAEs, stochastic
• Analysis & visualization tools
– E.g.: bifurcation, 2-D/3-D/4-D plotting
• Optimization & parameter searching
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Summary & Availability
• SBML
– Level 1 specification is publicly available
• http://www.cds.caltech.edu/erato
– Support being added by other groups to their apps
• SBW
– Preliminary test implementation completed
– Production version is now in development
• Draft API definition & other info available
– http://www.cds.caltech.edu/erato/sbw/docs
– Expect first public release in November at
ICSB 2001 (http://www.icsb2001.org)
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Outline
1) Background and motivations
I.e., why are we doing this?
2) Systems Biology Markup Language (SBML)
Model description language & exchange format
3) Systems Biology Workbench
Infrastructure for connecting software tools
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Scope of SBML
• Domain: biochemical network models
X2
k7*S3*S12
X0
K1*X0 - S1*K2
S3/Ki
Vmax*S1
Km+S1
S1
S2
k4*S2 - k5*S3
S3
k6*S3
X1
k3*S2
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