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Recent developments in the world of SBML (the Systems Biology Markup Language)
 

Recent developments in the world of SBML (the Systems Biology Markup Language)

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Presentation given on the first day of COMBINE 2013 in Paris, France, on September 16, 2013.

Presentation given on the first day of COMBINE 2013 in Paris, France, on September 16, 2013.

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    Recent developments in the world of SBML (the Systems Biology Markup Language) Recent developments in the world of SBML (the Systems Biology Markup Language) Presentation Transcript

    • Recent developments in the world of SBML (the Systems Biology Markup Language) Michael Hucka, Ph.D. Department of Computing + Mathematical Sciences California Institute of Technology Pasadena, CA, USA COMBINE 2013, Paris, September 2013 Email: mhucka@caltech.edu Twitter: @mhucka
    • Outline Background and motivation About SBML Recent developments Acknowledgements
    • Outline Background and motivation About SBML Recent developments Acknowledgements
    • “ The nature of systems biology” Bruggeman & Westerhoff, Trends Microbiol. 15 (2007).
    • Large-scale integrative models are growing
    • Many models have traditionally been published this way Problems: • Errors in printing • Missing information • Outright errors • Dependencies on implementation • Can be a huge effort to recreate Is it enough to communicate the model in a paper?
    • Is it enough to make your (software X) code available? It’s vital for good science: • Someone with access to the same software can try to run it, understand it, verify the results, etc. • Opinion: you should always do this in any case
    • Is it enough to make your (software X) code available? It’s vital for good science— • Someone with access to the same software can try to run it, understand it, verify the results, etc. • Opinion: you should always do this in any case But it’s still not ideal for communication of scientific results: • Doesn’t necessarily encode biological semantics of the model • What if they don’t have access to the same software? • What if they don’t want to use that software? • What if they want to use a different conceptual framework? • And how will people be able to relate the model to other work?
    • Different tools different interfaces & languages
    • Outline Background and motivation About SBML Recent developments Acknowledgements
    • SBML:alinguafranca forsoftware
    • Format for representing computational models of biological processes • Data structures + usage principles + serialization to XML • (Mostly) Declarative, not procedural—not a scripting language Neutral with respect to modeling framework • E.g., ODE, stochastic systems, etc. Important: software reads/writes SBML, not humans SBML = Systems Biology Markup Language
    • The raw SBML (as XML)
    • The raw SBML (as XML) Don’t work with it directly! Let software do it.
    • The process is central • Literally called“reaction”(not necessarily biochemical) • Participants are pools of entities of the same kind (“species”) • Species are located in containers (“compartments”) Models can further include: • Other constants & variables • Discontinuous events Core SBML concepts are fairly simple • Unit definitions • Annotations • Other, explicit math na1 A nb1 B+ nc1C f1(...) na2 A nd2 D+ ne2E f2(...) ... nc3 C nf3F f3(...) + ng3G
    • Core SBML constructs support many types of models Typical ODE models (e.g., cell differentiation) Conductance-based models (e.g., Hodgin-Huxley) Typically do not use SBML “reaction” construct, but instead use “rate rules” construct Neural models (e.g., spiking neurons) Typically use “events” for discontinuous changes Pharmacokinetic/dynamics models “Species”arenotrequiredtobebiochemicalentities Infectious diseases BioModels Database model #MODEL1008060001 BioModels Database model #BIOMD0000000451 BioModels Database model #BIOMD0000000020 BioModels Database model #BIOMD0000000127 BioModels Database model #BIOMD0000000234 Example of model type Example model List originally by Nicolas Le Novére
    • Many examples of SBML and software resources are available Accepted by dozens of journals * 100’s of software tools available today • Libraries: libSBML, JSBML • 250+ listed in SBML Software Guide † 1000’s of models available in SBML format today • ... in public databases, e.g., BioModels Database, Reactome • ... as supplementary data to published papers • ... in private repositories * http://sbml.org/Documents/Publications_known_to_accept_submissions_in_SBML_format † http://sbml.org/SBML_Software_Guide
    • NationalInstituteofGeneralMedicalSciences(USA) European Molecular Biology Laboratory (EMBL) JST ERATO Kitano Symbiotic Systems Project (Japan) (to 2003) JST ERATO-SORST Program (Japan) ELIXIR (UK) Beckman Institute, Caltech (USA) Keio University (Japan) International Joint Research Program of NEDO (Japan) Japanese Ministry of Agriculture Japanese Ministry of Educ., Culture, Sports, Science and Tech. BBSRC (UK) National Science Foundation (USA) DARPA IPTO Bio-SPICE Bio-Computation Program (USA) Air Force Office of Scientific Research (USA) STRI, University of Hertfordshire (UK) Molecular Sciences Institute (USA) SBML funding sources over the past 13+ years
    • Outline Background and motivation About SBML Recent developments Acknowledgements
    • Recent developments in software tools by the SBMLTeam
    • New features in the SBMLTest Suite SBML Test Suite = conformance-testing system for SBML software • Part 1: corpus of test models & expected numerical results - 1200+ cases, all tagged by features tested • Part 2: software facilities - Online assessment system - New: standalone test runner - New: online database of results http://sbml.org/Software/SBML_Test_Suite
    • New standalone SBMLTest Suite Runner Runs an SBML-compatible application through the test suite cases Written in Java + SWT — installers available for Mac OS, Windows, Linux
    • New database of SBMLTest Suite results Developed by Frank Bergmann
    • New database of SBMLTest Suite results Developed by Frank Bergmann
    • New database of SBMLTest Suite results Developed by Frank Bergmann
    • Example: RoadRunner
    • Recent developments in SBML
    • Evolution of SBML continues Today: SBML Level 3 • Level 3 Core provides framework for common models • Level 3 packages add additional constructs to the Core
    • Level 3 package What it enables Hierarchical model composition Models containing submodels ✔ Flux balance constraints Constraint-based models ✔ Qualitative models Petri net models, Boolean models ✔ Graph layout Diagrams of models ✔ Multicomponent/state species Entities w/ structure; also rule-based models draft Spatial Nonhomogeneous spatial models draft Graph rendering Diagrams of models draft Groups Arbitrary grouping of components draft Distributions Numerical values as statistical distributions in dev Arrays & sets Arrays or sets of entities in dev Dynamic structures Creation & destruction of components in dev Annotations Richer annotation syntax Status
    • SBML Level 3 package: Hierarchical Model Composition Defines syntax for composing models from other models (or fragments) Nicknamed‘comp’ Developed by Lucian Smith, Mike Hucka, Stefan Hoops, Chris Myers, Andrew Finney, Martin Ginkel, Ion Moraru, Wolfram Liebermeister Species ... Compartments ... Parameters ... Reactions ... Model“A” Core SBML Species ... Compartments ... Parameters ... Reactions ... Model“A” With hierarchical model composition Species ... Compartments ... Parameters ... Reactions ... Model“B” Species ... Compartments ... Parameters ... Reactions ... Model“C”
    • The‘comp’package supports multiple arrangements Species ... Compartments ... Parameters ... Reactions ... Model“A” Species ... Compartments ... Parameters ... Reactions ... Model“B” Separate files (possibly in databases) Species ... Compartments ... Parameters ... Reactions ... Model“C” Model“C” Model“D” Species ... Compartments ... Parameters ... Reactions ... Model“D” Model“B” Substitutions and deletions of entities can be defined
    • Results can be“flattened”to plain SBML Level 3 Core Implemented in libSBML Allows tools to read L3 +‘comp’models as if they were just plain L3 Species ... Compartments ... Parameters ... Reactions ... Model“A” Species ... Compartments ... Parameters ... Reactions ... Model“B” Species ... Compartments ... Parameters ... Reactions ... Model“C” Model“C” Model“D” Species ... Compartments ... Parameters ... Reactions ... Model“D” Model“B” Species ... Compartments ... Parameters ... Reactions ... Model“A” SBML Level 3 CoreOriginal SBML Level 3 Core + SBML‘comp’
    • Define syntax for constraint-based (e.g., flux-balance analysis) models • E.g. problem: optimize a specific property subject to constraints on reaction fluxes and other parameters Nicknamed‘fbc’ Developed by Brett Olivier and Frank Bergmann Implemented in libSBML & SBMLToolbox; supported in CMBPy, FAME, SBW Converters available to/from CORBA Toolbox SBML Level 3 package: Flux Balance Constraints
    • SBML Level 3 package: Qualitative Models Supports using discrete logical formalism – e.g., Boolean net, Petri, ... Nicknamed‘qual’ Adds data structures for: • Qualitative species – assume discrete levels or states (e.g., 0 or 1) - Unlike normal SBML species, which are quantities of stuff • Transitions, with inputs, outputs and function terms - Transition function terms evaluated at each time step Developed by Claudine Chaouiya, Sarah Keating, Duncan Berenguier, Aurélien Naldi, Denis Thieffry, Tomáš Helikar, Nicolas Le Novère, Martijn van Iersel Implemented in libSBML & JSBML; supported in GINsim, CellNOpt, Cell Collective Paper under review – manuscript at http://arxiv.org/abs/1309.1910
    • SBML Level 3 package: Layout Defines syntax for storing diagram layouts in SBML file • Does not define the rendering of the diagram - Rendering is the domain SBML Level 3 Rendering package Nicknamed‘layout’ Originally developed by Ralph Gauges, Ursula Rost, Sven Sahle, and Katja Wegner for SBML Level 2; updated for Level 3 by Frank Bergmann Implemented in libSBML & JSBML; supported in COPASI, SBW, others
    • Outline Background and motivation About SBML Recent developments Acknowledgements
    • Attendees at SBML 10th Anniversary Symposium, Edinburgh, 2010 Mike Hucka, Sarah Keating, Frank Bergmann, Lucian Smith, Andrew Finney, Herbert Sauro, Hamid Bolouri, Ben Bornstein, Maria Schilstra, Jo Matthews, Bruce Shapiro, Linda Taddeo, Akira Funahashi, Akiya Juraku, Ben Kovitz, Nicolas Rodriguez, Andreas Dräger SBML& JSBMLTeam: SBML Editors: Mike Hucka, Frank Bergmann, Sarah Keating, Nicolas Le Novère, Chris Myers, Lucian Smith, Stefan Hoops, Sven Sahle, James Schaff, DarrenWilkinson And a huge thanks to many others in the SBML and COMBINE communities for massive contributions to SBML development and continuing support SBML is the product of a wonderful, dedicated community
    • I’d like your feedback! You can use this anonymous form: http://tinyurl.com/mhuckafeedback