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Composite annotions for the physiome

Composite annotions for the physiome. Semantics of Biological Processes. Physiome — multiscale. Multiple structural scales. 12 organ systems. > 100 elements. >> 100,000 molecule types. >400 cell-part types. >600 cell types. 63 organ types. 2 bodies. meters. 10 -12. 1.

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Composite annotions for the physiome

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  1. Composite annotions for the physiome Semantics of Biological Processes

  2. Physiome — multiscale Multiple structural scales 12 organ systems > 100 elements >> 100,000 molecule types >400 cell-part types >600 cell types 63 organ types 2 bodies meters 10-12 1 extended from Hunter, P. J. & Borg, T. K. (2003). Nat Rev Mol Cell Biol 24(6):667-72.

  3. 12 organ systems > 100 elements >> 100,000 molecule types >400 cell-part types >600 cell types 63 organ types 2 bodies meters 10-12 1 seconds 10-6 19 fluid kinetics blood flow, respiratory gas flow… solid mechanics myocardial contraction, leg motion… electrophysiology transmembrane potential, action potential… metabolism, gene expression, cell signaling… chemical kinetics intracellular calcium dynamics… diffusion kinetics body temperature regulation… heat transfer Physiome — multidomain Multiple structural scales Multiple process domains

  4. Physiome — unfathomable complexity

  5. Physiome — informal representations physiology “maps” quantitative physiome

  6. Physiome as aggregate of discrete systems physical entities have biophysical property states physical processes change biophysical states • BioModels(n > 400) • CellML (n > 650) • JSim (n ≈ 300) • MatLab (?1000’s) • etc. (?)

  7. Challenge is model reuse and integration

  8. Composite annotions for the physiome — outline • Model searching and merging — SemGen • Meaning of code — SemSim, composite annotations • Challenges of composite annotation — patterns?

  9. Data structure Computation SemGen modeling based on biophysical semantics ontologies SemSim composite annotation structural knowledge structural relation FMA model code Physical entity GO model code ChEBI : Paorta PSysVein FSysArt Rartcap : FSysArt = …. property of physics knowledge Physical property OPB depends on Physical dependency

  10. CV+ JSim BARO VSM CV JSim JSim JSim Semantic model searching, merging — SemGen VSM SemSim model 1 merged model code 1 BARO 2 VSM+ 3 1 CV VSM+ 4 model code Gennari, J. H., M. L. Neal, B. E, Carlson, D. L. Cook (2008) Integration of multi-scale biosimulation models via light-weight semantics Pac Symp Biocomput (414-425)

  11. CV+ JSim VSM BARO CV JSim JSim JSim with displays... PhysioMap display VSM 1 5 1 BARO 2 VSM+ 3 1 CV VSM+ 4 Cook, D. L, Neal, M. L., Hoehndorf, R., Gkoutos, G. V., Gennari, J. H.: Representing physiological processes and their participants with PhysioMaps. J Biomed Semantics 2013. 4 Suppl 1:S2

  12. and aggregation. a “semantic physiome” Neal, M.L., D.L. Cook, and J.H. Gennari. An OWL knowledge base for classifying and querying collections of physiological models: A prototype human physiome. in ICBO2013. Montreal, Ont, CA: 24-Nov-2013.

  13. Data structure Computation Semantic representation of biophysical meaning SemSim (semantic simulation) model Coded in OWL (web ontology language) model code : Paorta PSysVein FSysArt Rartcap : FSysArt = …. depends on

  14. Data structure Computation Semantic representation of biophysical meaning SemSim model code : Paorta PSysVein FSysArt Rartcap : FSysArt = …. Physical property depends on Physical dependency

  15. Data structure Computation Semantic representation of biophysical meaning SemSim structural relation Physical entity model code : Paorta PSysVein FSysArt Rartcap : FSysArt = …. property of Physical property depends on Physical dependency

  16. Data structure Computation Annotate with reference knowledge ontologies SemSim structural knowledge structural relation FMA Physical entity GO model code ChEBI : Paorta PSysVein FSysArt Rartcap : FSysArt = …. property of physics knowledge Physical property OPB depends on Physical dependency

  17. Data structure Computation Biophysical meaning of model codewords ontologies SemSim composite annotation structural knowledge structural relation FMA Physical entity GO model code ChEBI : Paorta PSysVein FSysArt Rartcap : FSysArt = …. property of physics knowledge Physical property OPB depends on Physical dependency

  18. Composite annotations apply to models and data “P_a // aortic blood pressure” model physiology (real) data P-LV; V-LV; P-a; SNSact = .... ; : : 1 3 1 2 2 2 1 3 3 • Requirements: • correct biophysically • specific to modeling needs • unique and distinguishable 2 composite annotation OPB:Fluid pressureproperty_of FMA:Portion of bloodcontained_in FMA:Aorta Gennari, J.H., Neal, M. L., Galdzicki, M., Cook, D. L.: Multiple ontologies in action: Composite annotations for biosimulation models. J Biomed Inform 2009. 44:146-154.

  19. SemGen annotation — P_a // aortic blood pressure codeword list annotation tools source declarations

  20. Challenges: P_a // aortic blood pressure OPB:Fluid pressure property_of FMA:Portion of blood contained_inFMA:Cell cytoplasm Incorrect OPB:Fluid pressure property_of FMA:Portion of blood contained_inFMA:Aorta Same? How specific? OPB:Fluid pressure property_of FMA:Portion of blood contained_inFMA:Lumen of aorta OPB:Fluid pressure property_of FMA:Portion of blood contained_inFMA:Arch of aorta Same? OPB:Fluid pressure property_of FMA:Portion of blood contained_inFMA:Summit of arch of aorta OPB:Fluid pressure property_of FMA:Aorta OPB:Fluid pressure property_of FMA:Blood in aorta

  21. Composite annotations — state of the art? • Problem: It is difficult to curate unique identifiers for model variables. • Approach to a solution: • Restrict range of ontologies and logical relations • Stratify physical properties: state > rate > constitutive > control • Constrain and hide complexity with an annotation pattern language.

  22. Restrict to orthogonal reference ontologies physical property classes from: structural knowledge OPB - Ontology of Physics for Biology * PATO – Phenotype Ontology ? physics knowledge FMA OPB GO physical entity classes from: ChEBI FMA - Foundational Model of Anatomy * GO - Gene Ontology Cell Component UniProt – Protein Ontology IUPAC – Membrane proteins ChEBI - Chemical Entities of Biological Interest MA - Mouse Gross Anatomy Ontology ? CL – Cell Type Ontology ?

  23. Fluid kinetic Solid mechanics Chemical kinetic Electrochemical Diffusion kinetic Heat kinetic OPB:Dynamical domain and OPB:Dynamical property taxonomies OPB:Dynamical property Dynamical rate Dynamical state Dynamical flow rate Dynamical force Dynamical amount Dynamical momentum OPB:Dynamical domain Cook, D.L., F.L. Bookstein, and J.H. Gennari: Physical Properties of Biological Entities: An Introduction to the Ontology of Physics for Biology. PLoS ONE 2011. 6:e28708.

  24. Fluid kinetic Solid mechanics Chemical kinetic Electrochemical Diffusion kinetic Heat kinetic OPB:Dynamical domain and OPB:Dynamical property taxonomies OPB:Dynamical property Dynamical rate Dynamical state Dynamical flow rate Dynamical force Dynamical amount Dynamical momentum OPB:Dynamical domain ∫dt ∫dt

  25. OPB:Thermodynamic property OPB:Dynamical property OPB:Constitutive property OPB — generalized constitutive dependencies and properties flow rate R resistive d/dt ∫dt amount C capacitive force inductive L d/dt ∫dt momentum Cook, D.L., et al.: Ontology of physics for biology: representing physical dependencies as a basis for biological processes. Journal of Biomedical Semantics 2013. 4:41.

  26. Stratifying annotation concerns 1. participants and their state properties 2. processes and their dependencies 3. constitutive parameters VRestPulArtCaps capacitive ∫dt VPulArtCaps CPulArtCaps Blood in pulmonary capilaries PPulArtCaps resistive FPulValve RPulValve Blood in right ventricle PRV resistive RPulArtCaps FPulArtCaps ∫dt VPulVeins CPulVeins capacitive Blood in pulmonary veins VRestPulVeins PPulVeins resistive FPulVeins RPulVeins Blood in left atrium PLA

  27. OPB schema stratifies annotation concerns participant properties 2. processes dependencies 3. constitutive properties Cook, D.L., et al.: Ontology of physics for biology: representing physical dependencies as a basis for biological processes. Journal of Biomedical Semantics 2013. 4:41. Cook, D.L., F.L. Bookstein, and J.H. Gennari: Physical Properties of Biological Entities: An Introduction to the Ontology of Physics for Biology. PLoS ONE 2011. 6:e28708.

  28. Annotation pattern language? UniProt:macromolecule ChEBI:chemical OPB:Portion of chemical part_of part_of OPB:Chemical amount part_of FMA:Portion of body fluid FMA:Portion of extracellular fluid FMA:Portion of cell substance OPB:Fluid volume, pressure contained_in contained_in contained_in FMA:Anat. cavity FMA:Extracellular space FMA:Cell cavity OPB:Spatial extent bound_by bound_by FMA:Wall of organ FMA:Cell membrane part_of part_of OPB:Spatial property OPB:Spatial property FMA:Cell / Cell part FMA:Organ / Organ part OPB:Displacement, Force property OPB:Displacement, Force property part_of

  29. Composite annotions for the physiome — outline • SemGen: semantics-based model search and merging • SemSim, composite annotations of model meaning • OPB, FMA, GO, etc. as bio-knowledge resources • Strategies to constrain and simplify annotation tasks

  30. UM— Virtual Physiological Rat Project Dan Beard Brian Carlson Chris Thompson

  31. UW— Semantics of Biological Processes Group Maxwell Neal SemGen, PhysioMap Dan Cook biophysics, OPB, SemSim John Gennari Ontology, reasoning UNIVERSITY of WASHINGTON

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