applying the scientific method to simulation experiments

Applying the Scien.fic Method to Simula.on Experiments

Frank T. Bergmann, PhD California Ins8tute of Technology

University of Heidelberg [email protected]

Outline

Background & Introduc8on

Simula8on Experiment Descrip8on Markup Language – SED-‐ML

SoMware Support

Conclusion

Scien.fic Method

Scien&fic method – body of techniques for inves3ga3ng phenomena and acquiring new knowledge, as well as for correc&ng and integra&ng previous knowledge.

hOp://en.wikipedia.org/wiki/Scien8fic_method

Models

Models

Teusink et. al, 2003, DOI: 10.1046/j.1432-‐1327.2000.01527.x

Adapted from Michael Hucka

Species

Species

Reac.ons

Species

Reac8ons

Species

Rate Laws

Reac8ons

Systems Biology Markup Language (SBML) <?xml version="1.0" encoding="UTF-8"?> <sbml xmlns="http://www.sbml.org/sbml/level2/version4"

level="2" version="4"> <model id="BorisEJB" name="BorisEJB"> <listOfCompartments> <compartment id="compartment" size="1"/> </listOfCompartments> <listOfSpecies> <species id="MKKK" compartment="compartment"

initialConcentration="90"/> <species id="MKKK_P" compartment="compartment"

initialConcentration="10"/> [ . . . ] </listOfSpecies> <listOfParameters> <parameter id="J0_V1" value="2.5"/> <parameter id="J0_Ki" value="9"/> <parameter id="J0_n" value="1"/> <parameter id="J0_K1" value="10"/> [ . . . ] </listOfParameters> <listOfReactions> <reaction id="J0" reversible="false"> <listOfReactants> <speciesReference species="MKKK"/> </listOfReactants> <listOfProducts> <speciesReference species="MKKK_P"/> </listOfProducts> <listOfModifiers> <modifierSpeciesReference species="MAPK_PP"/> <modifierSpeciesReference species="MAPK_PP"/> </listOfModifiers> <kineticLaw> <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> [ . . . ]

SBML SoCware Guide

hOp://sbml.org/SBML_SoMware_Guide

Journals

• BioMedCentral (all journals) • Biophysical Journal • Computa8onal and Mathema8cal Biology •  FEBS Journal •  IET Systems Biology • Molecular Systems Biology • Nature (all NPG journals) • PLoS (all journals) • PNAS • Royal Society of Chemistry (all journals) • UCSD Molecule Pages

hOp://sbml.org/Documents/Publica8ons_known_to_accept_submissions_in_SBML_format

Models

Teusink et. al, 2003, DOI: 10.1046/j.1432-‐1327.2000.01527.x

Simula.on Experiments


Huang et. al, 1996, DOI: 10.1073/pnas.93.19.10078

biomodels.net/biomodels

biomodels.net/biomodels

Adapted from Michael Hucka



Cura8on tab of BioModel #9

Curator's comment: (updated: 15 Jul 2013 13:25:23 BST)#Figure 2B of the reference publication has been reproduced using Copasi 4.10 (Build 55). A logarithmic parameter scan over a range of "MAPKKK activator (Ras)" values with simultaneous calculation of the steady state was performed.#



Curator's comment: (updated: 15 Jul 2013 13:25:23 BST)#Figure 2B of the reference publication has been reproduced using Copasi 4.10 (Build 55). A logarithmic parameter scan over a range of "MAPKKK activator (Ras)" values with simultaneous calculation of the steady state was performed.#

Large scale integra.ve models …

Outline



SoMware Support

Conclusion

Simula.on Experiment Descrip.on Markup Language

SED-‐ML: Repeatable simula.on experiments

Model


Model Simula8on


Model Simula8on

Task


Model Simula8on

Task

Data Generators


Data Generators

Task

Reports

Model Simula8on

SED-‐ML Level 1 Version 1

SED-‐ML Level 1 Version 2

Data Generators

Task

Reports

Model Simula8on

Parameters

Repeated Task

Steady State

One Step

SED-‐ML L1V2

SED-‐ML Future

SED-‐ML

• Coverage • Simula8ons (stochas8c / determinis8c / steady state) • Parameter Scans (8me course / steady state / n-‐dimensional) • Dosing / Pulse experiments

• Work in Progress • Accessing Experimental Data, • Op8miza8on • Parameter Es8ma8on

Outline



SoMware Support

Conclusion

SED-‐ML Script Editor

hOp://libsedml.sf.net

SED-‐ML Web Tools

hOp://sysbioapps.dyndns.org/SED-‐ML_Web_Tools

Systems Biology Workbench

hOp://sbw.sf.net

CellDesigner

hOp://celldesigner.org

hOp://pysces.sf.net

SBSI – SED ED

hOp://sourceforge.net/projects/sbsi/

COPASI

hOp://www.copasi.org/

VCELL

hOp://www.nrcam.uchc.edu/

JWS Online

hOp://jjj.biochem.sun.ac.za/

Libraries

•  libSedML: .NET; BSD License hOp://libsedml.sourceforge.net

•  libSEDML: C/C++ with bindings for .NET, Java, Perl, Python, R, Ruby; BSD License, hOps://github.com/Bergmann/libsedml

•  jlibsedml: Java; MIT License hOp://sourceforge.net/projects/jlibsedml/

•  clibsedml,: C; BSD License hOp://sourceforge.net/projects/clibsedml

Outline



SoMware Support

Conclusion

Conclusions

• Opportunity: Simula8on Experiments as readily exchangeable as computa8onal models •  Independently of SoMware tools à independent verifica8on of results •  Con8nue in another tool right, where you leM off in one tool •  Possibility of full documenta8on of experiments •  Reuse the precisely same experiment for different models.

•  SoMware Support is growing, readily available in a number of tools.

Next Steps …

•  Finalize SED-‐ML Level 1 Version 2 • Prototype on Version 3

•  Export remaining experiments from the SBW Simula8on Tool •  Finish work on SED-‐ML exporters

•  SED-‐ML -‐-‐> Matlab •  SED-‐ML -‐-‐> Jarnac

Acknowledgements

•  SED-‐ML Editors: Frank T. Bergmann, Dagmar Waltemath, Jonathan Cooper, David Nickerson, Nicolas Le Novère, Andrew Miller, Richard Adams

• BioModels Support Team

•  SED-‐ML Community

• Ursula Kummer, Michael Hucka, Herbert Sauro

More Informa.on

•  SED-‐ML: hOp://sed-‐ml.org hOp://8nyurl.com/sed-‐ml-‐l1v2-‐rc hOps://lists.sourceforge.net/lists/lis8nfo/sed-‐ml-‐discuss/

•  SED-‐ML Web Tools: hOp://sysbioapps.dyndns.org/SED-‐ML_Web_Tools

•  SBML: hOp://sbml.org/ hOp://biomodels.net/biomodels