software for sbml today

Software for SBML Today

Michael Hucka, Ph.D.

Department of Computing + Mathematical SciencesCalifornia Institute of Technology

Pasadena, CA, USA

Email: mhucka@caltech.edu Twitter: @mhucka

HARMONY 2012, Maastricht, The Netherlands2

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.

SBML = Systems Biology Markup LanguageSBML = Systems Biology Markup Language

3

SBML is a lingua franca for

software (not humans)

4

The process is central

• Called a “reaction” in SBML

• Participants are pools of entities (species)

Models can further include:

• Other constants & variables

• Compartments

• Explicit math

• Discontinuous events

Basic SBML concepts are fairly simple

• Unit definitions

• Annotations

5

Well-stirred compartments

Some basics of SBML core model encoding

c

n

6

c

n

protein A protein B

gene mRNAn mRNAc

Species pools are located in compartments

7

Reactions can involve any species anywhere

c

n

protein A protein B

gene mRNAn mRNAc

8

Reactions can cross compartment boundaries

c

n

protein A protein B

gene mRNAn mRNAc

9

Reaction/process rates can be (almost) arbitrary formulas

c

n

protein A protein B

gene mRNAn mRNAc

f1(x)

f2(x)

f3(x)f4(x)

f5(x)

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“Rules”: equations expressing relationships in addition to reaction sys.

c

n

protein A protein B

gene mRNAn mRNAc

f1(x)

f2(x)

f3(x)

g1(x)g2(x)

.

.

.

f4(x)

f5(x)

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“Events”: discontinuous actions triggered by system conditions

c

n

protein A protein B

gene mRNAn mRNAc

f1(x)

f2(x)

f3(x)

g1(x)g2(x)

.

.

.

Event1: when (...condition...), do (...assignments...)

Event2: when (...condition...), do (...assignments...)

...

f4(x)

f5(x)

12

Annotations: machine-readable semantics and links to other resources

Event1: when (...condition...), do (...assignments...)

Event2: when (...condition...), do (...assignments...)

...

c

n

protein A protein B

gene mRNAn mRNAc

f1(x)

f2(x)

f3(x)

g1(x)g2(x)...

f4(x)

f5(x)

“This event represents ...”

“This is identified by GO id # ...”

“This is an enzymatic reaction with EC # ...”

“This is a transport into the nucleus ...” “This compartment

represents the nucleus ...”

13

Scope of SBML encompasses many types of models14

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 models14

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

Find examples inBioModels Databasehttp://biomodels.net/biomodels

14

Today: spatially homogeneous models

• Metabolic network models

• Signaling pathway models

• Conductance-based models

• Neural models

• 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

Find examples inBioModels Databasehttp://biomodels.net/biomodels

14

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

15

Find SBML software

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

15

SBML Software Guide, with different views (same data)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)

2011:

• Expanded survey

- Basis of this talk

17

New version of the SBML software survey

18

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

Question: Which of the following categories best describe your software? (Check all that apply.)

Purposes of the software systems

Total number of software tools

Simulation software

Analysis s/w (in addition, or instead of, simulation)

Creation/model development software

Visualization/display/formatting software

Utility software (e.g., format conversion)

Data integration and management software

Repository or database

Framework or library (for use in developing s/w)

S/w for interactive env. (e.g., MATLAB, R, ...)

Annotation software0 20 40 60 80

11

13

13

14

16

23

31

31

40

42

20

Question: Which of the following categories best describe your software? (Check all that apply.)

Purposes of the software systems

Total number of software tools

Simulation software

Analysis s/w (in addition, or instead of, simulation)

Creation/model development software

Visualization/display/formatting software

Utility software (e.g., format conversion)

Data integration and management software

Repository or database

Framework or library (for use in developing s/w)

S/w for interactive env. (e.g., MATLAB, R, ...)

Annotation software0 20 40 60 80

11

13

13

14

16

23

31

31

40

42

20

Question: Which of the following categories best describe your software? (Check all that apply.)

Purposes of the software systems

Total number of software tools

Simulation software

Analysis s/w (in addition, or instead of, simulation)

Creation/model development software

Visualization/display/formatting software

Utility software (e.g., format conversion)

Data integration and management software

Repository or database

Framework or library (for use in developing s/w)

S/w for interactive env. (e.g., MATLAB, R, ...)

Annotation software0 20 40 60 80

11

13

13

14

16

23

31

31

40

42

1/4 1/2 3/4

20

Question: Which of the following categories best describe your software? (Check all that apply.)

Purposes of the software systems

Total number of software tools

Simulation software

Analysis s/w (in addition, or instead of, simulation)

Creation/model development software

Visualization/display/formatting software

Utility software (e.g., format conversion)

Data integration and management software

Repository or database

Framework or library (for use in developing s/w)

S/w for interactive env. (e.g., MATLAB, R, ...)

Annotation software0 20 40 60 80

11

13

13

14

16

23

31

31

40

42

21

Question: Which of the following categories best describe your software? (Check all that apply.)

Purposes of the software systems

Total number of software tools

Simulation software

Analysis s/w (in addition, or instead of, simulation)

Creation/model development software

Visualization/display/formatting software

Utility software (e.g., format conversion)

Data integration and management software

Repository or database

Framework or library (for use in developing s/w)

S/w for interactive env. (e.g., MATLAB, R, ...)

Annotation software0 20 40 60 80

11

13

13

14

16

23

31

31

40

42

?

21

Question: Which of the following categories best describe your software? (Check all that apply.)

Purposes of the software systems

Total number of software tools

Simulation software

Analysis s/w (in addition, or instead of, simulation)

Creation/model development software

Visualization/display/formatting software

Utility software (e.g., format conversion)

Data integration and management software

Repository or database

Framework or library (for use in developing s/w)

S/w for interactive env. (e.g., MATLAB, R, ...)

Annotation software0 20 40 60 80

11

13

13

14

16

23

31

31

40

42

?

Low

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Question: Regardless of whether your software provides simulation capabilities, what modeling frameworks does the package support when working with SBML files?

Mathematical frameworks

Ordinary differential equations (ODE)

Discrete stochastic simulation

Discontinuous event handling

Differential-algebraic equations (DAE)

Logical/Boolean networks

Delay-differential equations (DDE)

Partial differential equations (PDE)

None of the above, or other framework0 20 40 60 80

20

8

9

11

17

25

28

54

Total number of software tools

22

Question: Regardless of whether your software provides simulation capabilities, what modeling frameworks does the package support when working with SBML files?

Mathematical frameworks

Ordinary differential equations (ODE)

Discrete stochastic simulation

Discontinuous event handling

Differential-algebraic equations (DAE)

Logical/Boolean networks

Delay-differential equations (DDE)

Partial differential equations (PDE)

None of the above, or other framework0 20 40 60 80

20

8

9

11

17

25

28

54

Total number of software tools

E.g.: FBA

22

Question: Which features of SBML can your software recognize and act on?

Specific SBML-specific characteristics

Species, reactions, parameters, and/or compartments

Work with reaction kinetics

Work with stoichiometric relationships/maps

Work with other mathematical relationships

Work with conditional discontinuous events

Work with time delays

Other, or not applicable

0 20 40 60 80

14

10

27

32

46

48

65

Total number of software tools

23

Other supported standards

MIRIAMSBO

SBGNBioPAXCellML

SED-MLMFAML

PNMLSBOL

0 5 10 15 20

111

33

613

1416

Total # software tools supporting other standards

(Warning: different scale)

Question: Which other standards does your software support?

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Operating systems supported by the 81 tools

Microsoft Windows

Apple Mac OS

Linux

Web browser

0 20 40 60 807

0

0

8

26

58

64

69

Total Only this

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Operating systems supported by the 81 tools

Microsoft Windows

Apple Mac OS

Linux

Web browser

0 20 40 60 807

0

0

8

26

58

64

69

Total Only this

!

25

Availability of software

Fee-based2%

Free98%

Fees for academics

Fee-based10%

Free90%

Fees for non-academics

Notavail.21%

Codeavailable

79%

Is source code available?

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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

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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 AgricultureJapanese 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)

Fund

ing a

ckno

wled

gmen

ts

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A huge thank you to the community

Attendees at SBML 10th Anniversary Symposium, Edinburgh, 2010

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