SBML (the Systems Biology Markup Language)
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The document discusses the Systems Biology Markup Language (SBML), a format for representing quantitative models in computational biology, emphasizing the need for effective sharing of models and reproducibility in simulations. It outlines the evolution of SBML, its specifications, and the community's ongoing efforts to develop interoperable standards and software tools. Key lessons learned from the SBML development process highlight the importance of stakeholder engagement, simplicity, and formal procedures.
![Basic SBML concepts are simple
The reaction is central: a process occurring at a given rate
• Participants are pools of entities (species)
f ([A],[B],[P ],...)
na A + nb B − − − − − − → np P
−−−−−−
f (...)
nc C −−
−→ nd D + ne E + nf F
.
.
.
Models can further include:
• Other constants & variables • Unit definitions
• Compartments • Annotations
• Explicit math
• Discontinuous events
Tuesday, July 26, 2011 9](https://image.slidesharecdn.com/mhucka-cabig-icr-2011-07-120706232709-phpapp02/85/SBML-the-Systems-Biology-Markup-Language-9-320.jpg)
![Basic SBML concepts are simple
The reaction is central: a process occurring at a given rate
• Participants are pools of entities (species) Can be anything
conceptually
f ([A],[B],[P ],...)
na A + nb B − − − − − − → np P
−−−−−− compatible
f (...)
nc C −−
−→ nd D + ne E + nf F
.
.
.
Models can further include:
• Other constants & variables • Unit definitions
• Compartments • Annotations
• Explicit math
• Discontinuous events
Tuesday, July 26, 2011 9](https://image.slidesharecdn.com/mhucka-cabig-icr-2011-07-120706232709-phpapp02/85/SBML-the-Systems-Biology-Markup-Language-10-320.jpg)
SBML (the Systems Biology Markup Language)
- 1. SBML (the Systems Biology Markup Language) Michael Hucka, Ph.D. (On behalf of many people) California Institute of Technology Pasadena, California, USA Tuesday, July 26, 2011 1
- 2. Roadmap What is SBML? What is the SBML community like today, and how did it get there? Acknowledgments Tuesday, July 26, 2011 2
- 3. SBML Tuesday, July 26, 2011 3
- 4. Subject matter: computational modeling Data Experiments Models Focus on mechanistic, computational models • Preferrably not statistical or curve-fitting models, but dynamical models expressing hypothesized physical & chemical mechanisms - Equations refer to identifiable processes - Parameters have physical interpretations Tuesday, July 26, 2011 4
- 5. Example: Tyson 1991 model of cell cycle Tuesday, July 26, 2011 5
- 6. Goal: reproducible and reusable models and simulations Tuesday, July 26, 2011 6
- 7. To achieve that, need effective means for sharing models Not enough simply to publish lists of equations! Need a software-independent format • No single package answers all needs • New techniques ( new tools) are developed continuously • Different packages have different niche strengths - Strengths are often complementary Need to capture both • Mathematical content of a model • Semantic content of a model Tuesday, July 26, 2011 7
- 8. SBML = Systems Biology Markup Language Format for representing quantitative models • Defines object model + rules for its use - Serialized to XML Neutral with respect to modeling framework • ODE vs. stochastic vs. ... A lingua franca for software But: not a procedural description Tuesday, July 26, 2011 8
- 9. Basic SBML concepts are simple The reaction is central: a process occurring at a given rate • Participants are pools of entities (species) f ([A],[B],[P ],...) na A + nb B − − − − − − → np P −−−−−− f (...) nc C −− −→ nd D + ne E + nf F . . . Models can further include: • Other constants & variables • Unit definitions • Compartments • Annotations • Explicit math • Discontinuous events Tuesday, July 26, 2011 9
- 10. Basic SBML concepts are simple The reaction is central: a process occurring at a given rate • Participants are pools of entities (species) Can be anything conceptually f ([A],[B],[P ],...) na A + nb B − − − − − − → np P −−−−−− compatible f (...) nc C −− −→ nd D + ne E + nf F . . . Models can further include: • Other constants & variables • Unit definitions • Compartments • Annotations • Explicit math • Discontinuous events Tuesday, July 26, 2011 9
- 11. Example of model type Example model Signaling pathway models BioModels Database model #BIOMD0000000153 Conductance-based models • “Rate rules” for temporal evolution of quantitative parameters BioModels Database model #BIOMD0000000020 Neural models • “Events” for discontinuous changes in quantitative parameters BioModels Database model #BIOMD0000000127 Pharmacokinetic/dynamics models • “Species” is not required to be a biochemical entity BioModels Database model #BIOMD0000000234 Infectious diseases BioModels Database model #MODEL1008060001 Scope of SBML is not limited to one kind of model Tuesday, July 26, 2011 10
- 12. 300+ curated & annotated models in BioModels Database Tuesday, July 26, 2011 11
- 13. SBML Software Guide Tuesday, July 26, 2011 12
- 14. SBML Software Guide Find SBML software Tuesday, July 26, 2011 12
- 15. Number of software systems supporting SBML 300 229 as of July 14 ↓ 200 100 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 (counted in middle of each year) http://sbml.org/SBML_Software_Guide Tuesday, July 26, 2011 13
- 16. libSBML Reads, writes, validates SBML Latest stable version: 5.0.0 • Hundreds of rules for helping http://sbml.org/Software/libSBML to ensure correct SBML Unit checking & conversion Well-tested Core is written in portable C++ Runs on Linux, Mac, Windows APIs for C, C++, C#, Java, Octave, Perl, Python, Ruby, MATLAB (some via SWIG) Developed by Sarah Keating, Frank Can use Expat, libxml2, or Xerces Bergmann, Ben Bornstein, Akiya Jouraku, & Mike Hucka, with Open-source under LGPL substantial contributions from many other people Tuesday, July 26, 2011 14
- 17. Current state of SBML specifications Specification document available from http://sbml.org/Documents Newest: Level 3 Version 1 Core • Oct. 2010 About SBML “Levels”: • Levels help manage significant restructuring of SBML architecture • Levels coexist - E.g., Level 2 models will remain valid and exist for a long time • A Level is not solely a vertical change (i.e., more features)—there is horizontal change too (i.e., changes to existing elements) Tuesday, July 26, 2011 15
- 18. What is the SBML community like today, and how did it get there? Tuesday, July 26, 2011 16
- 19. What happened in the beginning? Circa 2000: Hamid Bolouri contacted groups having relevant software tools • Organized workshops & set goal: develop interoperability • Funding from Japanese agency JST (via Hiroaki Kitano & John Doyle) • 3 core developers worked on software infrastructure at Caltech Early years: focus on software infrastructure (SBW) • SBML was a component, but not sole (or even primary) focus Eventually: SBML turned out to be more popular • 2 core developers remained (Finney & Hucka), focused on SBML • More groups/software supported SBML • Original dev. process was ad hoc, but involved constant feedback - Hosted biannual workshops where intense discussions were held Tuesday, July 26, 2011 17
- 20. What happened when SBML gained users? Implemented editorial board • Bootstrapped with heavily-involved people (Hucka, Finney, Le Novère) - After that, turned to community-based elections • Editors are volunteers, serve for limited terms Implemented electronic polling for major decisions & voting Continued biannual meetings • Split into forum meetings and hackathons Developed a somewhat more formal process • http://sbml.org/Documents/SBML_Development_Process Tuesday, July 26, 2011 18
- 21. SBML’s scope is widening to support more types of models Package Z Package X Package Y SBML Level 3 Core SBML Level 3 is designed around concept of modular additions • A package adds constructs & capabilities Models declare which packages they use • Applications tell users which packages they support Package development can be decoupled Tuesday, July 26, 2011 19
- 22. What’s happening now? SBML Level 3 Package specification & software development is ongoing Creation of COMBINE: Computational Modeling in Biology Network • Goal: coordinate development of interoperable, non-overlapping standards covering all aspects of modeling in biology • http://co.mbine.org/ Tuesday, July 26, 2011 20
- 23. Model Procedures Results Representation format SBRML Minimal info ? requirements Semantics— Mathematical Other annotations annotations annotations Standards emerging for related but out-of-scope areas Tuesday, July 26, 2011 21
- 24. Some lessons about what think we got right Start with actual stakeholders • Address real needs, not perceived ones Don’t include the kitchen sink • Smaller & simpler easier to understand, describe, implement Provide transparent & inclusive process • Critical to legitimacy—people must see their ideas being considered Engage people, constantly, in many ways • Not just electronic forums, email, etc., but face-to-face • Not getting responses? Find a new approach! Have independent leaders/organizers/shepherds • Avoid the appearance of bias or agenda Tuesday, July 26, 2011 22
- 25. Some lessons about what definitely got wrong Inadequate testing before freezing/releasing Not managing complexity creep • Feature changes between SBML versions make support harder Not formalizing the process sufficiently • Need “Requests for Comments” procedures, voting procedures, etc. • Only put most of this in place in recent years Underestimating how much time it takes to do everything • Also: democratic, open processes move slowly Tuesday, July 26, 2011 23
- 26. Roadmap What is SBML? What is the SBML community like today, and how did it get there? Acknowledgments Tuesday, July 26, 2011 24
- 27. People on SBML Team & BioModels Team SBML Team BioModels.net Team Michael Hucka Nicolas Le Novère Sarah Keating Camille Laibe Frank Bergmann Nicolas Rodriguez Lucian Smith Nick Juty Nicolas Rodriguez Vijayalakshmi Chelliah Linda Taddeo Michael Schubert Akiya Joukarou Lukas Endler Akira Funahashi Chen Li Kimberley Begley Harish Dharuri Bruce Shapiro Lu Li Andrew Finney Enuo He Ben Bornstein Mélanie Courtot Ben Kovitz Alexander Broicher Hamid Bolouri Arnaud Henry Herbert Sauro Visionaries Marco Donizelli Jo Matthews Hiroaki Kitano Maria Schilstra John Doyle Tuesday, July 26, 2011 25
- 28. National Institute of General Medical Sciences (USA) European Molecular Biology Laboratory (EMBL) ELIXIR (UK) Beckman Institute, Caltech (USA) Keio University (Japan) JST ERATO Kitano Symbiotic Systems Project (Japan) (to 2003) National Science Foundation (USA) International Joint Research Program of NEDO (Japan) JST ERATO-SORST Program (Japan) Japanese Ministry of Agriculture Japanese Ministry of Educ., Culture, Sports, Science and Tech. BBSRC (UK) DARPA IPTO Bio-SPICE Bio-Computation Program (USA) Air Force Office of Scientific Research (USA) STRI, University of Hertfordshire (UK) Molecular Sciences Institute (USA) Agencies to thank for supporting SBML & BioModels.net Tuesday, July 26, 2011 26
- 29. Where to find out more SBML http://sbml.org libSBML & JSBML http://sbml.org/Software BioModels Database http://biomodels.net/biomodels MIRIAM http://biomodels.net/miriam SED-ML http://biomodels.net/sed-ml SBO http://biomodels.net/sbo KiSAO http://www.ebi.ac.uk/compneur-srv/kisao/ TEDDY http://www.ebi.ac.uk/compneur-srv/teddy/ Thank you for your time! Tuesday, July 26, 2011 27
- 30. Extra slides Tuesday, July 26, 2011 28
- 31. Evolution of features took time & practical experience Level 1 Level 2 Level 3 predefined math user-defined functions user-defined functions functions text-string math notation MathML subset MathML subset reserved namespaces for no reserved namespaces no reserved namespaces annotations for annotations for annotations no controlled annotation RDF-based controlled RDF-based controlled scheme annotation scheme annotation scheme no discrete events discrete events discrete events default values defined default values defined no default values monolithic monolithic modular Tuesday, July 26, 2011 29
- 32. Level 3 package Active? libSBML 5 implementation? Graph layout ✓ Groups ✓ Spatial ✓ Flux balance constraints ✓ Hierarchical composition ✓ (in progress) Multicomponent species ✓ Annotations ✓ Graph rendering ✓ Distribution & ranges ✓ Qualitative models ✓ Dynamic structures Arrays & sets Tuesday, July 26, 2011 30
- 33. Model Entity element referenced relationship qualifier (optional) MIRIAM cross-references are simple triples { Data type identifier Data item identifier Annotation qualifier } (Required) (Required) (Optional) Format: URI chosen from Syntax & value space Controlled agreed-upon list depends on data type vocabulary term Tuesday, July 26, 2011 31