Slides from presentation given at the Workshop on Interoperability in Scientific Computing during the 7th IEEE International Conference on e-Science Stockholm, Sweden, December 5, 2011.

1. A Profile of Today's SBML-Compatible
Software
Michael Hucka, Ph.D.
Control and Dynamical Systems
Dept. of Computing + Mathematical Sciences
California Institute of Technology
Pasadena, CA, USA
1

2. 1. Background
Outline
2. Survey results & discussion
3. Acknowledgments
2

3. 1. Background
Outline
2. Survey results & discussion
3. Acknowledgments
3

4. SBML = Systems Biology Markup Language
Format for representing computational models of biological processes
• Data structures + usage principles + serialization to XML
Neutral with respect to modeling framework
• E.g., ODE, stochastic systems, etc.
A lingua franca for software (not humans)
4

5. Basic SBML concepts are fairly simple
The reaction is central: a process occurring at a given rate
f ([A],[B],[P ],...)
na A + nb B ⇥ np P
f (...)
nc C ⇥ nd D + ne E + nf F
.
.
.
• Participants are pools of entities (species)
Models can further include:
• Other constants & variables • Unit definitions
• Compartments • Annotations
• Explicit math
• Discontinuous events
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6. Scope of SBML encompasses many types of models
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7. Today: spatially homogeneous models
• Metabolic network models
• Signaling pathway models
• Conductance-based models
• Neural models
• Pharmacokinetic/dynamics models
• Infectious diseases
Scope of SBML encompasses many types of models
6

8. Today: spatially homogeneous models
• Metabolic network models F i nd
BioM
exam
ples i
• Signaling pathway models
http:/
odels
Data
n
base
• Conductance-based models /biom
odels
.net/b
• Neural models iomo
dels
• Pharmacokinetic/dynamics models
• Infectious diseases
Scope of SBML encompasses many types of models
6

9. Today: spatially homogeneous models
• Metabolic network models F i nd
BioM
exam
ples i
• Signaling pathway models
http:/
odels
Data
n
base
• Conductance-based models /biom
odels
.net/b
• Neural models iomo
dels
• Pharmacokinetic/dynamics models
• Infectious diseases
Coming: SBML Level 3 package to support other types of models
• Spatially inhomogeneous models
• Qualitative/logical
Scope of SBML encompasses many types of models
6

10. SBML Level 1 SBML Level 2 SBML Level 3
predefined math functions user-defined functions user-defined 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
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11. Where to learn more: SBML.org—the SBML portal
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12. Where to learn more: SBML.org—the SBML portal
Find SBML software
8

13. SBML Software Guide, with different views (same data)
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14. Example: the software matrix
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15. Number of software systems supporting SBML
300
229 in July 14 ↓
200
100
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
(counted in middle of each year)
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16. How did we gather data on the software tools?
Historically (until mid-2000’s):
• Word of mouth at workshops & conferences
• Direct contact
Mid/late-2000’s to ~2010:
• Created electronic survey
• Citation alerts (e.g., Web of Science)
This year (2011):
• Expanded survey
- Basis of this talk
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17. 1. Background
Outline
2. Survey results & discussion
3. Acknowledgments
13

18. New version of the SBML software survey
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19. General features of the survey
Online, implemented using commercial survey website
28 questions
• Mix of multiple choice, fill-in-the-blank, and hybrid questions
85 responses by July 2011
• Removed incomplete responses
• 81 software tools left
Avoided “corrections” to data
15

20. Purposes of the software systems
Question: Which of the following categories best describe your software?
(Check all that apply.)
Simulation software 42
Analysis s/w (in addition, or instead of, simulation) 40
Creation/model development software 31
Visualization/display/formatting software 31
Utility software (e.g., format conversion) 23
Data integration and management software 16
Repository or database 14
Framework or library (for use in developing s/w) 13
S/w for interactive env. (e.g., MATLAB, R, ...) 13
Annotation software 11
0 20 40 60 80
Total number of software tools
16

21. Mathematical frameworks
Question: Regardless of whether your software provides simulation capabilities,
what modeling frameworks does the package support when working with SBML
files?
Ordinary differential equations (ODE) 54
Discrete stochastic simulation 28
Discontinuous event handling 25
Differential-algebraic equations (DAE) 17
Logical/Boolean networks 11
Delay-differential equations (DDE) 9
Partial differential equations (PDE) 8
None of the above, or other framework 20
0 20 40 60 80
Total number of software tools
17

22. General SBML-related characteristics
Import Supports
28% SBML Level 3
Import & 36% Does not yet
Export export
support Level 3
11% 60%
64%
Read SBML, write SBML, Percentage supporting
or both? SBML Level 3
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23. More specific SBML-specific characteristics
Question: Which features of SBML can your software recognize and act on?
Species, reactions, parameters, and/or compartments 65
Work with reaction kinetics 48
Work with stoichiometric relationships/maps 46
Work with other mathematical relationships 32
Work with conditional discontinuous events 27
Work with time delays 10
Other, or not applicable 14
0 20 40 60 80
Total number of software tools
19

24. Other supported standards
MIRIAM 16
SBO 14
SBGN 13
BioPAX 6
CellML 3
SED-ML 3
MFAML 1
PNML 1
SBOL 1
0 5 10 15 20
Total # software tools supporting other standards
20

25. Operating systems supported by the 81 tools
69
Microsoft Windows 8
64
Apple Mac OS 0
58
Linux 0
26
Web browser 7
0 20 40 60 80
Total Only this
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26. Availability of software
Fee-based Not
Fee-based
2% avail.
10%
21%
Code
Free Free available
98% 90% 79%
Fees for Fees for non- Is source code
academics academics available?
22

27. License choices
BSD 23
GPL 22
Custom license 13
LGPL 10
Creative Commons 4
Apache License 1
Artistic License 1
DARPA BioCOMP 1
MIT 1
None 5
0 20 40 60 80
Number of software tools
23

28. Final impressions
Some pleasing results
• Large variety, including tools offering features SBML can’t yet represent
- Hopefully stands as testament to SBML’s utility
• Nearly 80% are open source
Some disappointing results
• Low response turnout: 85 vs 230 tools in matrix
- Many still missing, but not 150
• Only 1/3 of tools support SBML Level 3
• Low support for MIRIAM
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29. 1. Background
Outline
2. Survey results & discussion
3. Acknowledgments
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30. Agencies to thank for supporting SBML
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)
JST ERATO-SORST Program (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)
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31. Core SBML Team
Frank Bergmann Sarah Keating Lucian Smith
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32. Attendees at SBML 10th Anniversary Symposium, Edinburgh, 2010
A huge thank you to the community
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