1. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Stefan Schulz, Martin Boeker, Holger Stenzhorn University Medical Center Freiburg, Institute of Medical Biometry and Medical Informatics Freiburg, Germany How Granularity Issues Concern Biomedical Ontology Integration MIE 2008

2. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion

3. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Background: emerging biomedical ontologies: standard descriptions of types of bio(medical) entities Challenge: interlink ontologies and enable interoperability Goal: share data both within and across disciplinary boundaries Proposal: BioTop, an integrative domain top level ontology for life science E Beisswanger, U Hahn, H Stenzhorn, S Schulz: BioTop: A Life Science Upper Domain Ontology. Forthcoming in Applied Ontology 2008 Introduction Problem 1 Problem 2 Problem 3 Conclusion

4. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Biomedical Ontologies… Domain Ontologies …are artifacts whose representational units are intended to designate classes of biomedical entities, their properties, and their interrelations Introduction Problem 1 Problem 2 Problem 3 Conclusion

5. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Transcription DNA-dependent transcription antisense RNA transcription mRNA transcription rRNA transcription tRNA transcription … (from Gene Ontology) Biomedical Ontologies… Domain Ontologies OBO (Gene Ontology, Sequence Ontology, Cell Ontology, OBI, ChEBI, Mouse Anatomy, FMA …) Introduction Problem 1 Problem 2 Problem 3 Conclusion

6. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Transcription DNA-dependent transcription antisense RNA transcription mRNA transcription rRNA transcription tRNA transcription … (from Gene Ontology) Upper Ontologies… Domain Ontologies OBO (Gene Ontology, Sequence Ontology, Cell Ontology, OBI, ChEBI, Mouse Anatomy, FMA …) Onto- logies limited to domain- independent categories Introduction Problem 1 Problem 2 Problem 3 Conclusion

7. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Transcription DNA-dependent transcription antisense RNA transcription mRNA transcription rRNA transcription tRNA transcription … (from Gene Ontology) Upper Ontologies Domain Ontologies OBO (Gene Ontology, Sequence Ontology, Cell Ontology, OBI, ChEBI, Mouse Anatomy, FMA …) Upper Ontology BFO DOLCE Entity Continuant Dependent Continuant Realizable Entity Function Role Independent Continuant Object Object Aggregate Occurrent Introduction Problem 1 Problem 2 Problem 3 Conclusion

8. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Transcription DNA-dependent transcription antisense RNA transcription mRNA transcription rRNA transcription tRNA transcription … (from Gene Ontology) Middle-level ? Domain Ontologies OBO (Gene Ontology, Sequence Ontology, Cell Ontology, OBI, ChEBI, Mouse Anatomy, FMA …) Upper Ontology BFO DOLCE Entity Continuant Dependent Continuant Realizable Entity Function Role Independent Continuant Object Object Aggregate Occurrent Organism Body Part Cell Cell Component Tissue Protein Nucleic Acid DNA RNA Biological Function Biological Process Introduction Problem 1 Problem 2 Problem 3 Conclusion

9. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Transcription DNA-dependent transcription antisense RNA transcription mRNA transcription rRNA transcription tRNA transcription … (from Gene Ontology) Top Domain Ontologies Domain Ontologies OBO (Gene Ontology, Sequence Ontology, Cell Ontology, OBI, ChEBI, Mouse Anatomy, FMA …) Upper Ontology BFO DOLCE Entity Continuant Dependent Continuant Realizable Entity Function Role Independent Continuant Object Object Aggregate Occurrent Organism Body Part Cell Cell Component Tissue Protein Nucleic Acid DNA RNA Biological Function Biological Process Introduction Problem 1 Problem 2 Problem 3 Conclusion

10. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration BioTop Lower-level alignment Upper Ontology Top Domain Ontology Domain Ontologies BFO OBO (Gene Ontology, Sequence Ontology, Cell Ontology, OBI, ChEBI, Mouse Anatomy, FMA …) GENIA Ontology GFO-Bio Simple Bio Upper Ontology DOLCE Introduction Problem 1 Problem 2 Problem 3 Conclusion

11. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration BioTop Upper-level alignment BFO Introduction Problem 1 Problem 2 Problem 3 Conclusion

12. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion

13. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration BioTop Upper-level alignment BFO Introduction Problem 1 Problem 2 Problem 3 Conclusion

14. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion Object or FiatObjectPart? Independent Continuant Object Fiat Object Part Object Aggregate Continuant An independent continuant entity that is spatially extended, maximally self-connected and self-contained (the parts are not separated from each other by spatial gaps), and possesses an internal unity; the identity of substantial objects is independent of that of other entities and can be maintained through time and through loss and gain of parts and qualities. Examples: an organism, a chair, a cell, a lung, an apple. An independent continuant entity that is part of a object but is not demarcated by any physical discontinuities. Examples: upper and lower lobes of the left lung, the dorsal and ventral surfaces of the body, the east side of Copenhagen, the lower right portion of a human torso. BFO FiatObjectPart

15. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion Object or FiatObjectPart? Independent Continuant Object Fiat Object Part Object Aggregate Continuant Bodily Organ BioTop ? FiatObjectPart

16. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Lung Surface vs. Pleural Space: Bona Fide Boundary (physical discontinuity) Lung Hilus: Entry of Bronchi, veins and arteries. Fiat Boundary (no physical discontinuity) Object or FiatObjectPart? Introduction Problem 1 Problem 2 Problem 3 Conclusion

17. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration “Nearly all seemingly well-delimited parts of biological organisms exhibit somewhere continuous spatial transitions into neighboring anatomical parts, which can be viewed in different ways by different disciplines. They have to be delineated partly by fiat before they can be spoken of in a well defined way.” Schulz & Johansson: Continua in Biological Systems. The Monist, 2007 Object or FiatObjectPart? Introduction Problem 1 Problem 2 Problem 3 Conclusion

18. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion Object or FiatObjectPart? Independent Continuant Object Fiat Object Part Object Aggregate Continuant Siamese Twin BioTop …before separation BFO

19. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion Object or FiatObjectPart? BFO Independent Continuant Object Fiat Object Part Object Aggregate Continuant Siamese Twin BioTop …after separation

20. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion Object vs. ObjectAggregate

21. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion Object vs. ObjectAggregate BFO Continuant Independent Continuant Object Fiat Object Part Object Aggregate An independent continuant entity that is spatially extended, maximally self-connected and self-contained (the parts are not separated from each other by spatial gaps), and possesses an internal unity; the identity of substantial objects is independent of that of other entities and can be maintained through time and through loss and gain of parts and qualities. Examples: an organism, a chair, a cell, a lung, an apple. An independent continuant entity that is a mereological sum of separate objects. Examples: a heap of stones, a group of commuters on the subway, a collection of bacteria, a flock of geese, the patients in a hospital, a symphony orchestra.

22. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion Object vs. ObjectAggregate Continuant Independent Continuant Object Fiat Object Part Object Aggregate BioTop Biological Object ? BFO

23. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration E.coli Object An independent continuant entity that is spatially extended, maximally self-connected and self-contained (the parts are not separated from each other by spatial gaps), and possesses an internal unity; the identity of substantial objects is independent of that of other entities and can be maintained through time and through loss and gain of parts and qualities. Examples: an organism, a chair, a cell, a lung, an apple. Introduction Problem 1 Problem 2 Problem 3 Conclusion Object vs. ObjectAggregate

24. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration E.coli Object vs. ObjectAggregate Object Object Aggregate Introduction Problem 1 Problem 2 Problem 3 Conclusion

25. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration E.coli Object vs. ObjectAggregate Object Object Aggregate Introduction Problem 1 Problem 2 Problem 3 Conclusion

26. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration H H H Object vs. ObjectAggregate Object Object Aggregate Introduction Problem 1 Problem 2 Problem 3 Conclusion

27. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration H H H H H H H H H H H H Object vs. ObjectAggregate ! Object Aggregate Object Introduction Problem 1 Problem 2 Problem 3 Conclusion

28. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration H H H H H H H H H 0,0001% nuclei 99,9999% empty space “filled” by probability distributions of electrons Every Biological Object is an ObjectAggregate! Object Aggregate Object Introduction Problem 1 Problem 2 Problem 3 Conclusion An independent continuant entity that is a mereological sum of separate objects.

29. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion

30. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Problem 3: What are “separate objects”? E.coli Object Aggregate An independent continuant entity that is a mereological sum of separate objects. Examples: a heap of stones, a group of commuters on the subway, a collection of bacteria, a flock of geese, the patients in a hospital, a symphony orchestra. E.coli Introduction Problem 1 Problem 2 Problem 3 Conclusion

31. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Problem 3: What are “separate objects”? Object E.coli An independent continuant entity that is spatially extended, maximally self-connected and self-contained (the parts are not separated from each other by spatial gaps), and possesses an internal unity; the identity of substantial objects is independent of that of other entities and can be maintained through time and through loss and gain of parts and qualities. Examples: an organism, a chair, a cell, a lung, an apple. Introduction Problem 1 Problem 2 Problem 3 Conclusion

32. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Problem 3: What are “separate objects”? E.coli Object Object Aggregate An independent continuant entity that is a mereological sum of separate objects. Examples: a heap of stones, a group of commuters on the subway, a collection of bacteria, a flock of geese, the patients in a hospital, a symphony orchestra. E.coli An independent continuant entity that is spatially extended, maximally self-connected and self-contained (the parts are not separated from each other by spatial gaps), and possesses an internal unity; the identity of substantial objects is independent of that of other entities and can be maintained through time and through loss and gain of parts and qualities. Examples: an organism, a chair, a cell, a lung, an apple. Introduction Problem 1 Problem 2 Problem 3 Conclusion

33. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration strength of connection mechanic adhesion Hydrogen Bridges surfaces chemical bonds Van- der- Waals Metallic Non Polar Covalent Polar Covalent Ionic Continuum of physical connection electro- static adhesion Introduction Problem 1 Problem 2 Problem 3 Conclusion

34. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Continuum between Types of Chemical Bonds

35. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Seperatedness / Connectedness Depends on –kinds of surfaces and mechanic adhesion and cohesion forces –types of chemical bonds –strengths of chemical bonds –number of chemical bonds Is a continuous property, and therefore problematic as a criterion for the upper level distinction of ontological categories Introduction Problem 1 Problem 2 Problem 3 Conclusion

36. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion

37. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration BFO 3 rd level categories challenged by Granularity-dependent notion of self- containedness and unity of objects Granularity-dependent view of objects as collection of particles Continuum of physical connection BFO uses ill-defined criteria of highest-level ontological distinctions Introduction Problem 1 Problem 2 Problem 3 Conclusion

38. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Consequences for upper ontology integration Critique of domain level ontology (BioTop) by applying the rigor of an upper level ontology Critique of the upper level ontology by assessing the appropriateness of upper level categories from the perspective of the domain level Practical conclusion for BioTop: exclude subclasses of BFO:IndependentContinuant Introduction Problem 1 Problem 2 Problem 3 Conclusion

39. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration Introduction Problem 1 Problem 2 Problem 3 Conclusion Consequences for upper ontology integration Continuant Object Fiat Object Part Object Aggregate BioTop BFO BioTop Independent Continuant

40. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration BioTop Metrics: BioTop is freely available at: http://purl.org/biotop BioTop discussion forum: biotop@googlegroups.com BootSTREP (FP6 - 028099 ) project: http://www.bootstrep.eu Introduction Problem 1 Problem 2 Problem 3 Conclusion

41. Stefan Schulz, Martin Boeker, Holger Stenzhorn: How Granularity Issues Concern Biomedical Ontology Integration