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The Canonical Life. Barry Smith http://ontology.buffalo.edu/smith. Ontology ( Phil. ). = the science of the types of objects, qualities, proesses, events, funktions, environments, relations ... in all spheres of reality. Google hits (in millions) 12.10.06. ontology 24.0

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The Canonical Life


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    1. The Canonical Life Barry Smith http://ontology.buffalo.edu/smith http://org.buffalo.edu

    2. Ontology (Phil.) • = the science of the types of objects, qualities, proesses, events, funktions, environments, relations ... in all spheres of reality http://org.buffalo.edu

    3. Google hits (in millions) 12.10.06 • ontology 24.0 • ontology + philosophy 4.6 • ontology + information science 7.4 • ontology + database 11.1 http://org.buffalo.edu

    4. http://org.buffalo.edu

    5. ontology (computer science) • (roughly) the construction of standardized classification systems designed to make databases compatible with each other http://org.buffalo.edu

    6. National Center for Biomedical Ontology • $18.8 mill. NIH Roadmap Center • Stanford Medical Informatics • University of San Francisco Medical Center • Berkeley Drosophila Genome Project • Cambridge University Department of Genetics • The Mayo Clinic • University at Buffalo Department of Philosophy http://org.buffalo.edu

    7. From chromosome to disease http://org.buffalo.edu

    8. genomics • transcriptomics • proteomics • reactomics • metabonomics • phenomics • behavioromics • connectomics • toxicopharmacogenomics • bibliomics • … legacy of Human Genome Project http://org.buffalo.edu

    9. http://org.buffalo.edu

    10. we need to know where in the body we need to know what kind of disease process we need semantic annotation of data = we need ontologies http://org.buffalo.edu

    11. how create broad-coverage semantic annotation systems for biomedicine? covering: in vitro biological phenomena model organisms humans http://org.buffalo.edu

    12. OBO Foundry Project • ontology developers in the life sciences have agreed in advance to accept a growing set of best practices in ontology development to ensure interoperability and additivity of annotations • http://obofoundry.org http://org.buffalo.edu

    13. http://org.buffalo.edu

    14. http://org.buffalo.edu

    15. http://org.buffalo.edu

    16. When a gene is identified • three types of questions need to be addressed: • 1. Where is it located in the cell? • 2. What functions does it have on the molecular level? • 3. To what biological processes do these functions contribute? http://org.buffalo.edu

    17. where in the cell ? what kind of molecular function? what kind of biological process ? http://org.buffalo.edu

    18. GO’s three ontologies molecular functions biological processes cellular components http://org.buffalo.edu

    19. Three granularities: • Cellular (for components) • Molecular (for functions) • Organ + organism (for processes) http://org.buffalo.edu

    20. http://org.buffalo.edu

    21. The Granularity Gulf • most existing data-sources are of fixed, single granularity • many (all?) clinical phenomena cross granularities http://org.buffalo.edu

    22. GO’s three ontologies biological process molecular function cellular component http://org.buffalo.edu

    23. GO’s three ontologies cellular process organism-level biological process molecular function cellular component http://org.buffalo.edu

    24. Normalization of Granular Levels molecular function organism-level biological process cellular process molecule cellular component organism http://org.buffalo.edu

    25. need to separate function from activity http://org.buffalo.edu

    26. organism-level biological process cellular process molecular process organism-level biological function cellular function molecular function molecule cellular component organism http://org.buffalo.edu

    27. types of process • stochastic processes (Brownian motion of blood cells) • accidents (heart penetrated by bullet) • functionings (heart pumping) (elite processes) • side-effects (heart beating) • malfunctionings ... http://org.buffalo.edu

    28. organism-level biological process cellular process molecular process functioning functioning functioning organism-level biological function cellular function molecular function molecule cellular component organism http://org.buffalo.edu

    29. organism-level process cellular process molecular process functionings functionings functionings organism-level biological function cellular function molecular function The new age of teleology http://org.buffalo.edu

    30. What does “function” mean? • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s survival • the function is this disposition http://org.buffalo.edu

    31. Problem of aging and death • are their parts of the organism involved in bringing about aging processes? • is this their function? http://org.buffalo.edu

    32. Problem of reproductive organs • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s survival http://org.buffalo.edu

    33. Problem of reproductive organs • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to a group’s survival http://org.buffalo.edu

    34. Problem of reproductive organs • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to genes’ survival http://org.buffalo.edu

    35. Functions are organized in a modular hierarchy • The function of each functional part is: to contribute to the functioning of the whole • we need to understand ‘function’ in relation to the actual environing whole of the part in question http://org.buffalo.edu

    36. What do the kidneys do? The function of the kidney is to purify blood http://org.buffalo.edu

    37. How does a kidney work? The nephron is the cardinal functional unit of the kidney http://org.buffalo.edu

    38. Nephron Functions 10 functional segments 15 different cell types http://org.buffalo.edu

    39. Challenge • Can we provide an account of the functions of sexual organs within this framework • an entity has a biological function if and only if it is part of an organism and has a disposition to act reliably in such a way as to contribute to the organism’s survival http://org.buffalo.edu

    40. Function is what gives rise to normal activity • But: that sperm function (to penetrate the ovum) is rare http://org.buffalo.edu

    41. This is a screwdriver This is a good screwdriver This is a broken screwdriver This is a heart This is a healthy heart This is an unhealthy heart Functions http://org.buffalo.edu

    42. Functions and Prototypes • In its functioning, a heart creates a four-dimensional process shape. Good hearts create other process shapes than sick hearts do. http://org.buffalo.edu

    43. Prototypes functioning http://org.buffalo.edu

    44. poor functioning http://org.buffalo.edu

    45. malfunctioning http://org.buffalo.edu

    46. not functioning at all http://org.buffalo.edu

    47. What clinical medicine is for • to eliminate malfunctioning by fixing broken body parts • (or to prevent the appearance of malfunctioning by intervening e.g. at the molecular level) http://org.buffalo.edu

    48. What is health • Boorse: the state of an organism is theoretically healthy, i.e., free from disease, in so far as its mode of functioning conforms to the natural design of that kind of organism • = all its functional parts function in such a way as to promote survival and reproduction http://org.buffalo.edu

    49. The Gene Ontology • is a canonical ontology – it represents only what is normal in the realm of (molecular) functioning • = what pertains to normal (‘wild type’) organisms (in all species) http://org.buffalo.edu

    50. The GO is a canonical representation • “The Gene Ontology is a computational representation of the ways in which gene products normally function in the biological realm” • Nucl. Acids Res. 2006: 34. http://org.buffalo.edu