Dr' Eduardo Mendoza

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BioSPICE a modeling platform for UP Life
Sciences Research?

• Dr. Eduardo Mendoza
• 2004 MLSI Lecture Series
• Physics Department
• Mathematics Department Center for
  NanoScience
• University of the Philippines
  Ludwig-Maximilians-University
• Diliman Munich, Germany
• eduardom_at_math.upd.edu.ph
  Eduardo.Mendoza_at_physik.uni-muenchen.de

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Topics to be covered

• What is and why BioSPICE?
• BioSPICEs Software Architecture
• Basis OAA, SBML, BioSPICE MDL
• Components of BioSPICE 4.0
• ModSim Components BioCharon, JigCell
• The Dashboard
• For S-System Fans SIMPATHICA
• UPD Implementation Planning

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Acknowledgement

• Most of the slide images are re-used from
  presentations at the last (May 03) BioSPICE
  Principal Investigators Conference

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1. What is and why BioSPICE ?

• DARPA BioComputing Project
• Initiated mid-2001 (50 million)
• 2 Parts
• DNA Computing
• Computational Models of Intracellular Processes
  and Systems of Cells (now called BioSPICE)
• SPICE
• Originally Simulation Program for Integrated
  Circuit Evaluation
• DARPA Simulation Program for Intra-Cell
  Evaluation

• BioSPICE Principal Investigators
• Adam Arkin, UC Berkeley
• Roger Brent, The Molecular Sciences Institute,
  Berkeley
• John Byrne, University of Texas, Houston
• James Collins, Boston University
• John Doyle, Caltech
• Ron Fearing, UC Berkeley
• Tom Garvey, SRI International
• Megan Jewett, Brigham and Womens Hospital,
  Harvard
• David Kahaner, ATIP/ERATO
• James Liao, UCLA
• Bud Mishra, NYU Cold Spring Harbor Labs
• Arch Owen, BBN Technologies
• Harvey Rubin, U of Pennsylvania
• John Schwaber, Thomas Jefferson U
• John Tyson, Virginia Tech

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Key Computational challenges for Systems Biology

• Develop approaches for large complex systems
  encompassing multiple scales (in space and time)
  and with highly diversified components
• Establish "systems engineering-oriented" ways of
  collaboration among modelers, including use of
  standards and platforms for data schemes and
  software tools used

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BioSPICE Mission

• Provide bio-scientists a standard, scalable and
  easy-to-use modeling and simulation environment
  (as open source software) by
• Developing a model library (or kernel) of
  relevant biochemical processes and analytical
  tools
• Integrating this kernel into a simulation
  environment with links to relevant databases (eg
  genomic, protein interaction information)
• Including user interface and data visualization
  tools to facilitate use by experimenters
• Testing, refining and validating the models using
  a range of cell experiments

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Project Organization

• Semi-annual software releases (Linux, Windows)
• Software Integrator SRI International
  (www.sri.com)
• Guided by SEPDTF (System Engineering and Product
  Development Task Force, established 12/02)
• Semi-annual PI meeting
• BioSPICE Community (worldwide)

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S. Kumar
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2. BioSPICEs Software Architecture

• Architecture built on 3 Elements
• Open Agent Architecture (OAA)
• Systems Biology Markup Language (SBML)
• BioSPICE Model Definition Language (MDL)

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What is SBML?

• Language for representation and exchange of
  biochemical network models
• Problems addressed (Hucka et al 10/02)
• users often need to work with complementary
  resources from multiple tools gt manual
  re-encoding in each tool
• when simulators are no longer supported, encoded
  models become unusable
• Models published in peer-reviewed journals are
  not straightforward to examine and test as they
  use specific representation and environments.
  This also prevents a re-use strategy in building
  more complex models

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SBML Evolution

• Software Platfoms for Systems Biology forum
  initiated April 2000 by ERATO Symbiotic Systems
  Project
• Principal Investigators H. Kitano (Sony/Keio
  U), J. Doyle (Caltech)
• Modeling/Simulation teams involved
• Berkeley Biospice (Arkin, UC Berkeley)
• Cellerator (Shapiro/Mjolsness, Caltech)
• DBsolve (Goryanin, Glaxo-Wellcome Research, UK)
• E-Cell (Tomita, Keio U)
• Gepasi (Mendes, Virginia Tech)
• Jarnac (Sauro, Caltech/KGI)
• StochSim (Morton-Firth/Bray, Cambridge U)
• Virtual Cell (Schaff, U Connecticut)
• ProMoT/DIVA (Ginkel, MPI Magdeburg)
• CellML (Hedley, U Auckland Physiome Sciences)

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SBML Key Characteristics

• Based on XML ( further XML-based standards like
  MathML)
• Releases (called levels) community driven
  (sbml-discuss list)
• Key authors M. Hucka, A. Finney, H. Sauro
• Level 1 published Mar 01
• Level 2 published Jun 03
• Level 3 work in full progress
• More than 35 tools support SBML now
• Check www.sbml.org

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SBML 2 Model Definition
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SBML 2Example for a Rule
gt Need Tools!
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(as of mid-2003)
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Dashboard

• .

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3. ModSim Components BioCharon

• Contributors
• BioSketchPad BBN
• Charon UPenn

Simulation by Charon
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JigCell (Model Builder, Run Manager)
Contributor Virginia Tech

• Spreadsheet paradigm
• Model Spreadsheet
• reactions, name, type, equation,
• modifiers/constants)
• Constants, Species, Conservation Laws

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JigCell Comparator

• allows the user to perform a quantitative
  analysis on a collection of data sets
• consists of
• Experiment tab
• Transform Editor
• Model Tab
• Objective Editor
• Objective Tab

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4. The Dashboard
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5. For S-System fans SimPathica

• S-System ODE in power law formalism
• XS-System S-System with associated trace
  automata (work of Mishra et al)
• SimPathica software environment for XS-Systems

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SimPathica Architecture
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6. UPD Implementation Planning

• Computational Math Research Lab at Math initiated
• BioSPICE 4.0 (Linux)
• Operative by mid-February
• Testing of components for potential MLSI use
• Basis for projects for BS, MS theses
• PLAS (Windows) for S-System and DVD (Linux) for
  polynomial simulation (eg apoptosis)
• eCognition (Windows) for coral reef image
  analysis
• joint work with Computer Science planned
• Discussion with CSRC planned for a BioSPICE
  environment (demo use for other departments)

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Thanks for your attention !

• Questions?