Turning Biological Knowledge into Mathematical Models, Automatically
Transcript of Turning Biological Knowledge into Mathematical Models, Automatically
Turning Biological Knowledge into Mathematical Models, Automatically
Oliver Ruebenacker, Michael Blinov, Ion Moraru, Jim Schaff, University of Connecticut Health Center
Bob's Theory
Question: How do FUD, BBL, OMG interact? Bob the Biologist has a theory Now he needs to test it (simulation!)
Bob the Biologist
The Question
? ?
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FUD
OMGBBL
OMGBBL
LOL
FUD
IMHO
Bob's Solution
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)
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
Qualitative Bio Knowledge on WebPathway Commons (BioPAX Level 2): BioGRID, MSKCC Cancer Cell Map, HPRD, HumanCyc, SBCNY, IntAct, MINT, NCI/Nature PID, Reactome1,623 pathways, 585,000 interactions, 106,000 physical entities, 564 organismsBioPAX Level 3 being testedUniProt: 531,473 SwissProt, 16,504,022 TrEMBLChEBI: 26,091 entriesNCBI Taxonomy: 814,119 taxonsFoundational Model of Anatomy: 120,000+ terms
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;
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
Quantitative Bio versus ModelingModel = Biology + Method
Biology: biological reality; qualitative + quantitative; general + specific ( => BioPAX, SBPAX)
Method: cropping, filtering, merging, requirements, assumptions, simplifications, omissions, artifacts ( => VCell)
Model: Math (=> SBML, CellML)
Systems Biology Pathway Exchange (SBPAX)
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)
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)
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
How to get the molecular weight
For most common: Hardcode weight, e.g. for ATP, Ca, GTP
Metabolites: Download from ChEBI
Proteins: Get sequence from UniProt Calculate weight from sequence Add modifications (e.g. phosphorylations)
Using the VCell Model DB
Create statistics of all public models (some filtering) Classify by compartments, species, reactions Group species by ChEBI classes and UniProt
keywords Find correlations between compartment
sizes, initial conditions, kinetic parameters To create new models, find similar existing
models, calculate numbers based on patterns/correlations.
Acknowledgements VCell: Jim Schaff, Michael Blinov, Ion Moraru, Dan
Vasiliescu, Xintao Wei, Fei Gao, Anu Lakshminarayana
BioPAX: Emek Demir, Gary Bader, 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
Virtual Cell (Model View)Virtual Cell (Pathway View)
http://sbpax.org http://vcell.org