The ERATO Systems Biology Workbench
description
Transcript of The ERATO Systems Biology Workbench
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The ERATO Systems Biology Workbench
Hamid Bolouri
ERATO Kitano Systems Biology ProjectCalifornia Institute of Technology &
University of Hertfordshire, UK
Project PIs: Hiroaki Kitano and John Doyle
Software development team: Andrew Finney, Michael Hucka, Herbert Sauro
Collaborators:Adam Arkin (BioSpice), Dennis Bray (StochSim), Igor Goryanin (DBsolve),
Les Loew (VirtualCell), Pedro Mendes (Gepasi), Masaru Tomita (Ecell)
Acknowledgements: Mark Borisuk, Eric Mjolsness, Tau-Mu Yi
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Resource Sharing, Motivation
Tool 7
Tool 3
Tool 4
Tool 2
Tool 6
Tool 5
Tool 1
Multistate reactions/stochastic
Reaction/Diffusion
Visualization of networks
Optimization
Bifurcation analysis
Handle large systems
Our goal:
provide software infrastructure to enable sharing of simulation software (current and future) and collaboration between developers (and modelers!)
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+CH3R
ATP ADPP
~flagellarmotor
Z
Y
PY~
PiB
B~P
Pi
CW-CH3
ATP
WA
MCPs
WA
+ATT
-ATT
MCPs
Signal transduction
MotionLigandbinding
Motor
Example Workbench application: bacterial chemotaxis
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Marlovits, Tyson, Novak, & Tyson, Biophysical Chemistry 72(1998) 169-184
k1k2
k3
k6
cyclin
cdc2
phosphorylation site
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View from the genome, c=cytoplasmic , n=nuclear , mN=maternal N, nN=nuclear N, MVLAS=maternal vegetally localised catenin activating system
N-dependent-TXF
late signal from ~ 7th cleavage micromeres
Mes-TXF
Endo-Mes-TXF Serrate
?
&
A1Micromere id. factor
ZygoticApical N
X
MVLAS
n
cLiClGSK-3
nN
mN
mes mes
mac / veg2 mic
Late signal from veg2
veg1 veg2
frizzled
endomes endomes
&
OR
Endo-mesGenes
mic mic
&
Endo-only-TXF
OTX
Endo16
A-V model v10, April 4th, 2000
& & & OR &
Endo- specificGenes
& &
Wnt8
&
Maternalactivator
MesGenes
OR
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ERATO Systems Biology Workbench: driving principles
• Integrate, don’t reinvent!– integrate existing simulators– use standard application integration methods
• object oriented, XML, Java and related technologies
• Accommodate future tools– minimize need for ad hoc solutions
• object oriented, XML, Java and related technologies
– XML & API standards for future contributors
• Make sure contributors benefit– symmetric plug-in infrastructure– open source code infrastructure software– widen user-base, but protect IPR of contributors
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Systems Biology Markup Language [SBML]
• A common XML format for biochemical networks
• Enables exchange of models between simulators
• Developed in collaboration with BioSpice, DBsolve, Gepasi, Jarnac, Ecell, StochSim, VirtualCell
• Available for public review since Sept 2000 at ftp://ftp.cds.caltech.edu/pub/caltech-erato/sbml/sbml.pdf
• Proposed extensions due 2nd Quarter 2001
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Example workbench plug-in modules
• Data filtering and preparation
– e.g. image processing, regression, clustering
• Database support
– e.g. web searching, storage management, translators, conflict resolution
• Model description tools
– scripts, languages, schematic tools
• Model preprocessing
– e.g. conserved quantities, redundancy removal
• Maths language / maths description support
• Equation solvers
– e.g. ODE, DAE, PDE, stochastic
• Analysis tools
– e.g. 2/3/4D graphing, bifurcation, MCA
• Optimization and parameter searching
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Example potential plug-ins from DBsolve
• Data filtering and preparation – regression to implicit and explicit algebraic equations
• Database support – direct data import from WITT, MPW, KEGG
• Model description tools – stoichiometric matrix
• Model preprocessing – conserved quantities & redundancy removal
• Maths language / maths description support– maths editor
• Equation solvers – mixed ODE + NAE, LSODE
• Analysis tools – 2D graphing, bifurcation, continuation, all steady states
• Optimization and parameter searching– Hooke & Jeeves, Levenburg-Marquardt
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Systems Biology Workbench - APIs
• APIs provided by the Workbench for simulators
– Will provide access to a spectrum of current tools
– Integration into 3rd party simulators will require:– SBML output
– One menu item associated with one external library call
– Available Q1 2001
– Lower level APIs for optimization, bifurcation, time-based simulation and data display will follow, Q2 2001
• APIs provided by simulators to plug into Workbench
– Existing collaborators
• no API conformance, we will interface to given APIs
• The minimum requirement:
– Either parse SBML, parse equivalent documented format or provide a model construction API
– Output some documented numeric format or structure
– Future contributors to SBW
• Standard API for independent development available Q2 2001
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Systems Biology Workbench - APIs
• APIs provided by the Workbench for simulators
– Will provide access to a spectrum of current tools
– Integration into 3rd party simulators will require:– SBML output
– One menu item associated with one external library call
– Available Q1 2001
– Lower level APIs for optimization, bifurcation, time-based simulation and data display will follow, Q2 2001
• APIs provided by simulators to plug into Workbench
– Existing collaborators
• no API conformance, we will interface to given APIs
• The minimum requirement:
– Either parse SBML, parse equivalent documented format or provide a model construction API
– Output some documented numeric format or structure
– Future contributors to SBW
• Standard API for independent development available Q2 2001
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Workbench Development Plan
Task Nov Dec Jan Feb Mar Apr May
Design
GUI and Simulation Engine (Sauro)
Stochastic Simulation (Gibson)
Bifurcation analysis (Goryanin)
Param. optimization (Mendes)
Multi-representation simulation
Linux Port
QA, Install etc