SBML (the Systems Biology Markup Language)                         Michael Hucka, Ph.D.                          (On behal...
Roadmap                         What is SBML?                         What is the SBML community like today, and how did i...
SBMLTuesday, July 26, 2011          3
Subject matter: computational modeling                                                       Data                         ...
Example: Tyson 1991 model of cell cycleTuesday, July 26, 2011                                             5
Goal: reproducible and reusable models and simulationsTuesday, July 26, 2011                                    6
To achieve that, need effective means for sharing models     Not enough simply to publish lists of equations!     Need a s...
SBML = Systems Biology Markup Language     Format for representing quantitative models        •      Defines object model +...
Basic SBML concepts are simple     The reaction is central: a process occurring at a given rate        •      Participants...
Basic SBML concepts are simple     The reaction is central: a process occurring at a given rate        •      Participants...
Example of model type                            Example model     Signaling pathway models                        BioMode...
300+ curated & annotated models in BioModels DatabaseTuesday, July 26, 2011                              11
SBML Software GuideTuesday, July 26, 2011   12
SBML Software Guide                         Find SBML softwareTuesday, July 26, 2011                        12
Number of software systems supporting SBML                 300                                                            ...
libSBML     Reads, writes, validates SBML                  Latest stable version: 5.0.0            •      Hundreds of rule...
Current state of SBML specifications     Specification document available from     	 http://sbml.org/Documents     Newest: L...
What is the SBML community like today, and how did it get there?Tuesday, July 26, 2011                                    ...
What happened in the beginning?     Circa 2000: Hamid Bolouri contacted groups having relevant software tools        •    ...
What happened when SBML gained users?     Implemented editorial board        •      Bootstrapped with heavily-involved peo...
SBML’s scope is widening to support more types of models                                     Package Z                    ...
What’s happening now?     SBML Level 3 Package specification & software development is ongoing     Creation of COMBINE: Com...
Model        Procedures     Results     Representation            format                                             SBRML...
Some lessons about what think we got right     Start with actual stakeholders        •      Address real needs, not percei...
Some lessons about what definitely got wrong     Inadequate testing before freezing/releasing     Not managing complexity c...
Roadmap                         What is SBML?                         What is the SBML community like today, and how did i...
People on SBML Team & BioModels Team                            SBML Team                           BioModels.net Team    ...
National Institute of General Medical Sciences (USA)   European Molecular Biology Laboratory (EMBL)   ELIXIR (UK)   Beckma...
Where to find out more                                     SBML http://sbml.org                         libSBML & JSBML htt...
Extra slidesTuesday, July 26, 2011                  28
Evolution of features took time & practical experience                         Level 1         Level 2                 Lev...
Level 3 package            Active?   libSBML 5 implementation?Graph layout                 ✓Groups                       ✓...
Model                                    Entity                         element                                referenced ...
Upcoming SlideShare
Loading in …5
×

SBML (the Systems Biology Markup Language)

1,213 views

Published on

Slides from presentation given to the July 27, 2011, caBIG teleconference on Integrative Cancer Research.

Published in: Technology
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,213
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
12
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

SBML (the Systems Biology Markup Language)

  1. 1. SBML (the Systems Biology Markup Language) Michael Hucka, Ph.D. (On behalf of many people) California Institute of Technology Pasadena, California, USATuesday, July 26, 2011 1
  2. 2. Roadmap What is SBML? What is the SBML community like today, and how did it get there? AcknowledgmentsTuesday, July 26, 2011 2
  3. 3. SBMLTuesday, July 26, 2011 3
  4. 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 interpretationsTuesday, July 26, 2011 4
  5. 5. Example: Tyson 1991 model of cell cycleTuesday, July 26, 2011 5
  6. 6. Goal: reproducible and reusable models and simulationsTuesday, July 26, 2011 6
  7. 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 modelTuesday, July 26, 2011 7
  8. 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 descriptionTuesday, July 26, 2011 8
  9. 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 eventsTuesday, July 26, 2011 9
  10. 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 eventsTuesday, July 26, 2011 9
  11. 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 modelTuesday, July 26, 2011 10
  12. 12. 300+ curated & annotated models in BioModels DatabaseTuesday, July 26, 2011 11
  13. 13. SBML Software GuideTuesday, July 26, 2011 12
  14. 14. SBML Software Guide Find SBML softwareTuesday, July 26, 2011 12
  15. 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_GuideTuesday, July 26, 2011 13
  16. 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 peopleTuesday, July 26, 2011 14
  17. 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. 18. What is the SBML community like today, and how did it get there?Tuesday, July 26, 2011 16
  19. 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 heldTuesday, July 26, 2011 17
  20. 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_ProcessTuesday, July 26, 2011 18
  21. 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 decoupledTuesday, July 26, 2011 19
  22. 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. 23. Model Procedures Results Representation format SBRML Minimal info ? requirements Semantics— Mathematical Other annotations annotations annotations Standards emerging for related but out-of-scope areasTuesday, July 26, 2011 21
  24. 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 agendaTuesday, July 26, 2011 22
  25. 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 slowlyTuesday, July 26, 2011 23
  26. 26. Roadmap What is SBML? What is the SBML community like today, and how did it get there? AcknowledgmentsTuesday, July 26, 2011 24
  27. 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 DoyleTuesday, July 26, 2011 25
  28. 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.netTuesday, July 26, 2011 26
  29. 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. 30. Extra slidesTuesday, July 26, 2011 28
  31. 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 modularTuesday, July 26, 2011 29
  32. 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 structuresArrays & setsTuesday, July 26, 2011 30
  33. 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 termTuesday, July 26, 2011 31

×