intro to sbml, at the 8th international cellml workshop, 2014

SBML: The Systems Biology Markup LanguageLucian Smith

Computing and Mathematical Sciences, Caltech (Mike Hucka)

Bioengineering, University of Washington (Herbert Sauro)

8th International CellML Workshop, session 6

SBML and CellML

Both solve same problem in different ways Facilitate model re-use and exchange. Translators

Can generally preserve all the math Cannot always preserve all the semantics

SBML vs. CellML

CellML Born in 1998 from a desire to create models Wider range of mathematical support Model repository examples from many fields

SBML Born in 2000 from a desire to exchange models Wider tool support (http://sbml.org/SBML_Software_Guide) Supports process-based modeling in its basic

semantics

SBML basics

Processes (‘reactions’)

S1 S2

SBML basics

Processes (‘reactions’)

S1

S2

S1

Implication:dS1/dt = -2*J0dS2/dt = J0 –

J1dS3/d5 = J1

SBML basics

Implied rates of change!

S1

S2

S1

J0

S2 S3J1

Implication:dS1/dt = -2*J0dS2/dt = J0 –

J1dS3/d5 = J1

SBML basics

Facilitates many different analyses: ODEs Stochastic Steady State Parameter minimization Bifurcation analysis [etc.]

SBML basics

‘Species’ amounts and/or concentrations Straight mathematics

dx/dt = f(P) (‘rate rules’) x = f(P) (‘assignment rules’) 0 = f(x, P) (‘algebraic rules’)

Events When (S1>3): S2 = z

Constraints x > f(P)

SBML basics

Semantic content Inherent semantics of SBML elements (reaction,

species, compartment, event, etc.) SBO terms (Systems Biology Ontology) Further annotations with RDF

SBML recent developments:packages Extensions to ‘core’ SBML Add new functionality Separate namespace Development uncoupled from core Sub-community driven Tool support (or non-support) cleaner Full list at http://sbml.org/Community/Wiki

SBML recent developments:hierarchical modeling Roughly equivalent to CellML ‘components’

Both: nested elements for modularity CellML: black box, declare once SBML: white box*, declarations overridden

Facilitates model re-use and incorporation ‘Flattened’ to core SBML ‘Antimony’ translations between CellML and

hierarchical SBML: http://bioinformatics.oxfordjournals.org/content/30/7/903

SBML recent developments:hierarchical modeling

SBML recent developments:flux balance constraints Reactions given plausible ranges instead of

specific rates (bounds) Conditional optima defined and analyzed

(objective functions) such as: Maximize growth in presence/absence of O2

Maximize growth with knockouts

SBML recent developments:qualitative modeling Modeling of states (vs. values)

Boolean or multi-state networks Petri nets

New SBML constructs that parallel Reactions and Species

SBML recent developments:layout package Developed as SBML Level 2 annotations Visualization of SBML models

In the works:SBML Level 3 version 2 Fix problems Add clarifications Semantic changes

More allowed MathML Better integration of core with packages

Full list at https://sourceforge.net/p/sbml/sbml-specifications/

In the works:Spatial modeling Allows modeling of reactions and species in

space

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519356/

In the works:Spatial modeling Allows modeling of reactions and species in

space Defines geometries

and mappings

In the works:Spatial modeling Allows modeling of reactions and species in

space Defines geometries and mappings Diffusion and Advection

In the works:Spatial modeling Allows modeling of reactions and species in

space Defines geometries and mappings Diffusion and Advection Status:

Draft specification available VirtualCell and Copasi have exchanged models for a

subset of full specification

In the works:Distributions Uses UncertML (http://uncertml.org/) Allows defining elements as coming from

distributions Allows drawing of values from distributions Status:

Draft specification available No implementations at this time

In the works:Arrays Extends MathML to allow vectors and matrices Allows definition of arrayed SBML elements Designed to mesh easily with hierarchical

modeling Status:

Draft specification available Test implementation in iBioSim

In the works:Multistate/Multicomponent models

In the works:Multistate/Multicomponent models Multistate

In the works:Multistate/Multicomponent models Multistate Multicomponent

In the works:Multistate/Multicomponent models Multistate Multicomponent Status:

Draft specification available Test implementation in Simmune

In the works:Rendering Extends ‘layout’ Allow specification of

colors/lines/etc. Status:

Level 2 annotation defined but not fully agreed on

Level 3 package in the works

Various test implementations

Questions?