Transcript SBPAX: Turning Bio Knowledge into Math Models, Automated Oliver Ruebenacker (PanGenX) SW 4 HCLS, Tue, Aug 28, 2012 www.sbpax.org www.sbpax.org SW 4 HCLS Aug 28

SBPAX: Turning Bio Knowledge into
Math Models, Automated
Oliver Ruebenacker (PanGenX)
SW 4 HCLS, Tue, Aug 28, 2012
www.sbpax.org
www.sbpax.org SW 4 HCLS Aug 28 2012
Biological Pathway Exchange
(BioPAX, www.biopax.org)
Molecular Pathways in OWL:
Physical Entities (Protein, DNA, RNA, Complex, Small
Molecule), Interactions (Conversion, Control, etc.),
States (Phosphorylations, etc.)
Cross-references to DBs (molecules, functions,
publications, etc)
Genes, provenance, evidence, etc.
Versions: Level 3 (2010), Level 4 in progress
Governance: community, elected editors
Tools: PaxTools, Online Validator, Cytoscape Plugin
Interoperability: Combine Core Standard
www.sbpax.org SW 4 HCLS Aug 28 2012
Qualitative Bio Knowledge on Web
Pathway Commons (BioPAX Level 2):
BioGRID, MSKCC Cancer Cell Map, HPRD, HumanCyc,
SBCNY, IntAct, MINT, NCI/Nature PID, Reactome
1,623 pathways, 585,000 interactions, 106,000 physical
entities, 564 organisms
BioPAX Level 3 being tested
UniProt: 531,473 SwissProt, 16,504,022 TrEMBL
ChEBI: 26,091 entries
NCBI Taxonomy: 814,119 taxons
Foundational Model of Anatomy: 120,000+ terms
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Systems Biology Pathway
Exchange (SBPAX, www.sbpax.org)
Integrated with BioPAX classes
 Extension to BioPAX L3 as SBPAX3
 Proposal for BioPAX L4
Arranges Systems Biology terms (e.g. Systems
Biology Ontology), numbers and units into
hierarchies
Units based on Units of Measurement
Expressions (UOME)
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Systems Biology Ontology (SBO)
Project by BioModels.net, curator Nick Juty
Comprehensive collection of SB-relevant terms,
hierarchical
Includes terms for many rate laws, parameters
and quantities
For rate laws, includes math expression and
references to SBO terms of the parameters
(e.g. term for Michaelis-Menten rate law refers
to term for Michaelis constant)
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Units of Measurement Expressions
(UOME)
UOME core: ontology to define units:
 By scaling, exponentiation, offset, product or
quotient of other units
 By reference to controlled vocabulary (e.g. UO)
UOME list: long list of predefined units (e.g.
micro mole per milligram per minute)
Can convert to SBML/VCell units
www.sbpax.org SW 4 HCLS Aug 28 2012
Quantitative Bio Knowledge on Web
SABIO-RK: SBML export, rich on SBO;
implemented BioPAX L3, SBPAX3 export;
Signaling Gateway Molecule Pages: 672
curated pages (interactions), large diversity of
quantitative values, BioPAX L3 and SBPAX3
export
MetaCyc, EcoCyc: collecting enzymatic rate
constants; SBML, BioPAX L3 export; SBPAX3
interest;
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Virtual Cell
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Time-course simulations:
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Physiological Model:
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Compartments (e.g. anatomical structures)
Abundancies (e.g. concentrations / molecule numbers)
Processes (e.g. chemical reactions)
Can be converted to math model
Math Model:
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Deterministic or stochastic
Spatial or compartmental
General differential equations
Openness:
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Open source, MIT- licensed
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Virtual Cell Architecture
Client:
Java app + native libs (Win, Linux, Mac)
Start from Web (JNLP)
Some standalone capacity
Talks to Server
Server:
Java, spawns solver processes, talks to database
Database:
Oracle (any SQL would do)
Solvers:
Processes run on cluster
Mostly C++
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Bob's Theory
Question: How do FUD, BBL, OMG interact?
Bob the Biologist has a theory
Now he needs to test it (simulation!)
FUD
FUD
LOL
?
?
?
Bob the
Biologist
IMHO
OMG
OMG
BBL
BBL
The Question
Bob's Theory
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A realistic Model for Bob's Theory
For realistic simulation, need some context
Bob's Theory (new exciting research)
The Context (stuff everyone knows already)
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Trends
Biological Details → Complete Knowledge
Knowledge → Computer-processable
Knowledge → Public
Computers → Much faster
Bio Models → Complete Biochem Details
Model Building → Automatic
Model Builder → Knowledgebase Frontend
www.sbpax.org SW 4 HCLS Aug 28 2012
Bio Knowledge from Web into VCell
Systems Biology Linker (SyBiL) at VCell:
Grab Bio Knowledge from Web to build and
annotate models
 Qualitative: Queries Pathway Commons, UniProt,
ChEBI; imports BioPAX (since years)
 Quantitiative: SBPAX3 from SGMP, SABIO-RK
www.sbpax.org SW 4 HCLS Aug 28 2012
Same Reality  Many Models
Model = Biology + Method
Biology: biological reality; qualitative +
quantitative; general + specific (  BioPAX,
SBPAX)
Method: cropping, filtering, merging,
requirements, assumptions, simplifications,
omissions, artifacts (  SED-ML)
Model: Math ( SBML, VCML, CellML)
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Demo
Demo of latest VCell features
www.sbpax.org SW 4 HCLS Aug 28 2012
Acknowledgements
 VCell: Jim Schaff, Michael Blinov, Ion Moraru, Dan
Vasiliescu, Xintao Wei, Fei Gao, Anu Lakshminarayana
 BioPAX: Emek Demir, Gary Bader, Igor Rodchenkov,
Andria Splendiani, Peter D'Eustachio, Huaiyu Mi
 Signaling Gateway Molecule Pages: Ashok Dinasarapu
 SBO: Nick Juty
 SABIO-RK: Wolgang Mueller, Martin Golebiewski, Ulrike
Wittig, Renate Kania, Lenneke Jong, Enkhjargal Algaa
"Stagnation and the search for truth are always opposites." Nadezhda Tolokonnikova
www.sbpax.org SW 4 HCLS Aug 28 2012