short summary of sbml and the sbml development processsbml.org/images/c/ca/sbml-2011-06.pdf ·...

Short Summary of SBML and the SBML Development Process

Michael Hucka, Ph.D.

Control and Dynamical SystemsDivision of Engineering and Applied Science

California Institute of TechnologyPasadena, CA, USA

1Monday, June 20, 2011

Format for representing quantitative models

• Defines object model + rules for its use

- Serialized to XML

Neutral with respect to modeling framework

• ODE vs. stochastic vs. ...

A lingua franca for software

• Not procedural

SBML = Systems Biology Markup Language


The reaction is central: a process occurring at a given rate

• Participants are pools of entities (species)

Models can further include:

• Other constants & variables

• Compartments

• Explicit math

• Discontinuous events

Basic parts of SBML

naA + nbBf([A],[B],[P ],...)−−−−−−−−−−−−→npP

ncCf(...)−−−→ ndD + neE + nfF

...

Can be anything conceptually compatible

• Unit definitions

• Annotations


Some basics of SBML model encoding

c

n

Well-stirred compartments



c

n

protein A protein B

gene mRNAn mRNAc

Species pools are located in compartments



c

n

protein A protein B

gene mRNAn mRNAc

Reactions can involve any species anywhere



c

n

protein A protein B

gene mRNAn mRNAc

Reactions can cross compartment boundaries


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)


“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)


“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...)


...

f4(x)

f5(x)




...


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 ...”


Basic structure of an SBML model & example XML

<Beginning of SBML model definition>List of function definitionsList of unit definitionsList of compartmentsList of speciesList of parametersList of initial assignmentsList of rulesList of “constraints”List of reactionsList of events<End of SBML model definition>

...

...

Conceptual XML

Most components are optional


<species metaid="metaid_0000009" id="species_3" compartment="c_1"> <annotation> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" > <rdf:Description rdf:about="#metaid_0000009"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.chebi:CHEBI%3A15996"/> <rdf:li rdf:resource="urn:miriam:kegg.compound:C00044"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </species>

SBML defines a syntax for annotations




<rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.chebi:CHEBI%3A15996"/> <rdf:li rdf:resource="urn:miriam:kegg.compound:C00044"/> </rdf:Bag>

Data references




<bqbiol:is>

</bqbiol:is>

Relationship qualifier


Current SBML specifications

Current specifications:

• Level 3 Version 1 Core

- 6 Oct. 2010

• Level 2 Version 4

- 22 Dec. 2008

• Level 1 Version 2

- 28 Aug. 2003

On Nature Precedings & sbml.org/Documents14Monday, June 20, 2011

Evolution of features took time & practical experience

Level 1 Level 2 Level 3predefined math

functionsuser-defined functions user-defined functions

text-string math notation MathML subset MathML subset

reserved namespaces for annotations

no reserved namespaces for annotations

no reserved namespaces for annotations

no controlled annotation scheme

RDF-based controlled annotation scheme

RDF-based controlled annotation scheme

no discrete events discrete events discrete events

default values defined default values defined no default values

monolithic monolithic modular


SBML Level 3 is modular:

• “Core” defines common aspects

• “Packages” add optional features

- Models declare which packages they use

- Tools can tell their users which packages they support

• Analogy to XML — XML is core, then there’s XPath, MathML, etc.

Rationale: even if a tool isn’t equipped to handle a given package, probably can still interpret some aspects of the model

Additional expected benefit: decouple development of individual L3 pkgs

Cannot keep growing the feature set indefinitely


Level 3 package Active? libSBML 5 implementation?

Graph layout

Groups

Spatial

Flux balance constraints

Hierarchical composition (in progress)

Multicomponent species

Annotations

Graph rendering

Distribution & ranges

Qualitative models

Dynamic structures

Arrays & sets

✓✓✓✓✓✓

✓✓

✓

✓✓


Using Level 3 packages in SBML models



Use XML namespaces to reference the package definition



Declare package is being used and whether interpreter

must be able to understand the package in order to produce the intended mathematical behavior


Using package constructs

Package constructs prefixed with package namespace


SBML Development Process Progress

http://sbml.org/Documents/SBML_Development_Process20Monday, June 20, 2011

Proc

ess

for

intr

oduc

ing

new

L3

pack

ages

Pre-proposal stage

Proposal stage

Proposal voting/selection stage

Proposal acceptance stage

Package specification development


Start

Is a relevantproposal already being

developed?

Is it goodenough (maybe with small

changes) for your goals?

Stop

Propose the idea on sbml-discuss

Do people agreethe idea and approach are

novel & worth doing?

Enter proposal idea & summary at http://sbml.org/issue-tracker

Develop proposal details & produce a document followingthe Level 3 proposal template.

Add proposal to the appropriate area in the SBML Level 3 section of the SBML.org Community Wiki.

Post on sbml-discuss to notify the SBML community about

the new proposal.

Iterate on proposal design based on feedback (if needed).

StopYes

No

No

Yes

No

Yes

You may wish to participate in the development of the existing proposal. Contact the authors.

Pre-

prop

osal

& p

ropo

sal s

tage

s

Pre-proposal stageProposal stage

Level 3 Proposal Flowchart


Proposal stage in more detail

Steps:

1. Use SBML issue tracker to logproposal intention

2. Use Level 3 package proposal template to write proposal

3. Have proposal added to table on http://sbml.org/Community/Wiki

4. Engage community via sbml-discuss mailing list

5. Iron out issues

http://sbml.org/issue-tracker


Proposal voting/selection stage

1. After a period of discussion, a formal vote can be called

2. SBML Editors create an electronic voting form

3. Chair of the SBML Editors calls for a vote

4. SBML Editors report the outcome

a. 50% or more vote to accept ➜ accepted

b. Over 50% vote to reject ➜ rejected

c. Otherwise ➜ revise

5. If accepted, SBML Editors form a Package Working Group (PWG)

a. Membership must contain at least one of the package propers + at least one SBML Editor (+ anyone else interested)

b. Mailing list attached to the PWG: sbml-label (e.g., sbml-multi)


Proposal acceptance stage

Is there only one proposal for this area?

• Yes ➜ Go to specification development stage

• No ➜ Select between alternatives

- (More discussion, voting, etc.—see process description)


Table on http://sbml.org/Community/Wiki


Representationformat

Model Procedures Results

Minimal inforequirements

Semantics—

Mathematical

Other

SBRML

?

annotations annotations annotations

(Credit: Nicolas Le Novère)27Monday, June 20, 2011

People on SBML Team & BioModels TeamSBML Team BioModels.net Team

Michael Hucka Nicolas Le NovèreSarah Keating Camille Laibe

Frank Bergmann Nicolas RodriguezLucian Smith Nick Juty

Nicolas Rodriguez Lukas EndlerLinda Taddeo Vijayalakshmi ChelliahAkiya Joukarou Chen LiAkira Funahashi Harish Dharuri

Kimberley Begley Lu LiBruce Shapiro Enuo HeAndrew Finney Mélanie CourtotBen Bornstein Alexander Broicher

Ben Kovitz Arnaud HenryHamid Bolouri Marco DonizelliHerbert SauroJo Matthews

Maria Schilstra

VisionariesHiroaki Kitano

John Doyle


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)

National Science Foundation (USA)

International Joint Research Program of NEDO (Japan)

JST ERATO-SORST Program (Japan)

Japanese Ministry of Agriculture

Japanese Ministry of Educ., Culture, Sports, Science and Tech.

BBSRC (UK)

DARPA IPTO Bio-SPICE Bio-Computation Program (USA)

Air Force Office of Scientific Research (USA)

STRI, University of Hertfordshire (UK)

Molecular Sciences Institute (USA)

Agencies to thank for supporting SBML & BioModels.net29Monday, June 20, 2011