Presentation given by Michael Hucka at HARMONY 2012, May 21-25, Department of Bioinformatics - BiGCaT, University of Maastricht, The Netherlands.

1. Software for SBML Today
Michael Hucka, Ph.D.
Department of Computing + Mathematical Sciences
California Institute of Technology
Pasadena, CA, USA
Email: mhucka@caltech.edu Twitter: @mhucka
HARMONY 2012, Maastricht, The Netherlands
2

2. 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.
3

3. afor
nc )
fra ans
ua m
ing t hu
is al o
ML are (n
SB tw
s of
4

4. The process is central
• Called a “reaction” in SBML
• Participants are pools of entities (species)
Models can further include: • Unit definitions
• Other constants & variables • Annotations
• Compartments
• Explicit math
• Discontinuous events
Basic SBML concepts are fairly simple
5

5. Some basics of SBML core model encoding
Well-stirred compartments
c
n
6

6. Species pools are located in compartments
c
protein A protein B
n
gene mRNAn mRNAc
7

7. Reactions can involve any species anywhere
c
protein A protein B
n
gene mRNAn mRNAc
8

8. Reactions can cross compartment boundaries
c
protein A protein B
n
gene mRNAn mRNAc
9

9. Reaction/process rates can be (almost) arbitrary formulas
c
protein A f1(x) protein B
n
f5(x) f2(x)
gene f4(x) mRNAn f3(x) mRNAc
10

10. “Rules”: equations expressing relationships in addition to reaction sys.
g1(x) c
g2(x) protein A f1(x) protein B
.
.
. n
f5(x) f2(x)
gene f4(x) mRNAn f3(x) mRNAc
11

11. “Events”: discontinuous actions triggered by system conditions
g1(x) c
g2(x) protein A f1(x) protein B
.
.
. n
f5(x) f2(x)
gene f4(x) mRNAn f3(x) mRNAc
Event1: when (...condition...), Event2: when (...condition...), ...
do (...assignments...) do (...assignments...)
12

12. Annotations: machine-readable semantics and links to other resources
“This is identified “This is an enzymatic
c
g1(x)by GO id # ...” reaction with EC # ...”
g2(x)
. protein A f1(x) protein B
.
“This is a transport
. n
into the nucleus ...” “This compartment
represents the nucleus ...”
f5(x) f2(x)
gene f4(x) mRNAn f3(x) mRNAc
“This event
represents ...”
Event1: when (...condition...), Event2: when (...condition...), ...
do (...assignments...) do (...assignments...)
13

13. Scope of SBML encompasses many types of models
14

14. 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
14

15. Today: spatially homogeneous models
• Metabolic network models F i nd
BioM
exam
ples i
• Signaling pathway models odels n
Data
http:/ 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
14

16. Today: spatially homogeneous models
• Metabolic network models F i nd
BioM
exam
ples i
• Signaling pathway models odels n
Data
http:/ base
• Conductance-based models /biom
odels
.net/b
• Neural models iomo
dels
• Pharmacokinetic/dynamics models
• Infectious diseases
Coming: SBML Level 3 packages to support other types
• E.g.: Spatially inhomogeneous models, also qualitative/logical
Scope of SBML encompasses many types of models
14

17. Where to learn more: SBML.org—the SBML portal
15

18. Where to learn more: SBML.org—the SBML portal
Find SBML software
15

19. SBML Software Guide, with different views (same data)
16

20. 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)
2011:
• Expanded survey
- Basis of this talk
17

21. New version of the SBML software survey
18

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

23. 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
20

24. 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
20

25. 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
1/4 1/2 3/4
S/w for interactive env. (e.g., MATLAB, R, ...) 13
Annotation software 11
0 20 40 60 80
Total number of software tools
20

26. 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
21

27. 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
21

28. 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 Low
0 20 40 60 80
Total number of software tools
21

29. 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
22

30. 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 E.g.: FBA
0 20 40 60 80
Total number of software tools
22

31. 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
23

32. Other supported standards
Question: Which other standards does your software support?
MIRIAM 16
SBO 14
SBGN 13
BioPAX 6
CellML 3
SED-ML 3
MFAML 1
PNML 1 (Warning:
SBOL 1 different scale)
0 5 10 15 20
Total # software tools supporting other standards
24

33. Operating systems supported by the 81 tools
Microsoft Windows 69
8
Apple Mac OS 0 64
Linux 0 58
Web browser 26
7
0 20 40 60 80
Total Only this
25

34. Operating systems supported by the 81 tools
!
Microsoft Windows 69
8
Apple Mac OS 0 64
Linux 0 58
Web browser 26
7
0 20 40 60 80
Total Only this
25

35. 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?
26

36. Final impressions
Some pleasing results
• Large variety, including tools with 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
• Low support for MIRIAM
27

37. National Institute of General Medical Sciences (USA)
European Molecular Biology Laboratory (EMBL)
ELIXIR (UK)
Funding acknowledgments
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)
28

38. Attendees at SBML 10th Anniversary Symposium, Edinburgh, 2010
A huge thank you to the community
29