1. Introduction to Ontologies for Environmental Biology Barry Smith http://ontology.buffalo.edu/smith

2. 2 Finnegans Web concept type class instance model representation data process property

3. Disciplines here involved GIS Ecology Environmental biology Various -omics disciplines Bioinformatics Medical Informatics Database science Semantic webists...

4. 4 Part 1: What is an Ontology?

5. 5 what cellular component? what molecular function? what biological process?

6. 6 natural language labels designed for use in annotations to make the data cognitively accessible to human beings and algorithmically tractable to computers

7. 7 compare: legends for maps

8. 8 common legends allow (cross-border) integration

9. 9 ontologies are legends for data

10. 10 compare: legends for diagrams

11. Ramirez et al. Linking of Digital Images to Phylogenetic Data Matrices Using a Morphological Ontology Syst. Biol. 56(2):283–294, 2007

12. 12 computationally tractable legends help integrate complex representations of reality help human beings find things in complex representations of reality help computers reason with complex representations of reality

14. ontologies are used to annotate data

15. but there are two kinds of annotations

16. 16 names of types

17. 17 names of instances

18. 18 A basic distinction type vs. instance science text vs. diary human being vs. Michael Ashburner

19. 19 A515287DC3300 Dust Collector Fan B521683Gilmer Belt C521682Motor Drive Belt Catalog vs. inventory

20. 20 Ontology types Instances

21. 21 An ontology is a collection of standardized names for types We learn about types in reality from looking at the results of scientific experiments captured in the form of scientific theories Ontologies provide the terminological scaffolding of scientific theories experiments relate to what is particular science describes what is general

22. siamese mammal cat organism thing types animal instances frog 22

23. 23 types vs. their extensions type {a,b,c,...} class of instances = a collections of particulars

24. 24 Extension =def The extension of a type A is the class of instances of A (the class of all entities to which the term ‘A’ applies)

25. 25 types vs. classes types {c,d,e,...} classes

26. 26 types vs. classes types extensions ~ defined classes

27. 27 Defined class =def member of Abba aged > 50 years pizza with > 4 different toppings red wine to serve with fish

28. 28 Part 2: The OBO Foundry

29. 29 what cellular component? what molecular function? what biological process?

30. The Gene Ontology

32. 32 Five bangs for your GO buck 1.based in biological science 2.cross-species data comparability (human, mouse, yeast, fly...) 3.cross-granularity data integration (molecule, cell, organ, organism) 4.cumulation of scientific knowledge in algorithmically tractable form 5.links people to software 6.part of Open Biomedical Ontologies (OBO) The Gene Ontology

33. 33 Entry point for creation of web- accessible biomedical data GO initially low-tech to encourage users Simple (web-service-based) tools created to support the work of biologists in creating annotations (data entry) OBO  OWL DL converters now making OBO Foundry annotated data immediately accessible to Semantic Web data integration projects

34. The OBO Foundry A suite of high quality interoperable reference ontologies to serve the annotation of biomedical data providing guidelines for those who need to create new ontology resources http://obofoundry.org

35. 35 RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO) The OBO Foundry building out from the original GO

36. Simple guidelines use singular nouns distinguish continuants from occurrents distinguish things from their qualities distinguish types from their instances do not use the weasel word ‘concept’

37. 37  OPENNESS: The ontology is open and available to be used by all.  FORMAL LANGUAGE: The ontology is in, or can be instantiated in, a common formal language.  ORTHOGONALITY: The developers of the ontology agree in advance to collaborate with developers of other OBO Foundry ontology where domains overlap.  CONVERGENCE: The developers agree to work torwards a single ontology for each domain.http://obofoundry.org/ CRITERIA

38. 38  UPDATE: The developers of each ontology commit to its maintenance in light of scientific advance, and to soliciting community feedback for its improvement.  IDENTIFIERS: The ontology possesses a unique identifier space within OBO.  VERSIONING: The ontology provider has procedures for identifying distinct successive versions.  DEFINITIONS: The ontology includes textual definitions for all terms. CRITERIA http://obofoundry.org/

39. 39  CLEARLY BOUNDED: The ontology has a clearly specified and clearly delineated content.  DOCUMENTATION: The ontology is well-documented.  USERS: The ontology has a plurality of independent users.  COMMON ARCHITECTURE: The ontology uses relations which are unambiguously defined following the pattern of definitions laid down in the OBO Relation Ontology. CRITERIA http://obofoundry.org/

40. 40 Foundry ontologies all work in the same way all are built to represent the types existing in a pre- existing domain and the relations between these types in a way which can support reasoning –we have data –we need to make this data available for semantic search and algorithmic processing –we create a consensus-based ontology for annotating the data –and ensure that it can interoperate with Foundry ontologies for neighboring domains

41. 41 Formal-Ontological Relations is_a part_of located_at depends_on is_boundary_of adjacent_to

42. 42 To support integration of ontologies relational expressions such as is_a part_of... should be used in the same way in all ontologies involved

43. 43 to define these relations properly we need to take account of both types and instances in reality

44. 44 Kinds of relations : Toronto instance_of city : Toronto part_of Ontario : waterfall part_of river

45. 45 is_a human is_a mammal all instances of the type human are as a matter of necessity instances of the type mammal

46. 46 Karen Eilbecksong.sf.net properties and features of nucleic sequences Sequence Ontology (SO) RNA Ontology Consortium(under development) three-dimensional RNA structures RNA Ontology (RnaO) Barry Smith, Chris Mungallobo.sf.net/relationshiprelations Relation Ontology (RO) Protein Ontology Consortium(under development) protein types and modifications Protein Ontology (PrO) Michael Ashburner, Suzanna Lewis, Georgios Gkoutos obo.sourceforge.net/cgi -bin/ detail.cgi? attribute_and_value qualities of biomedical entities Phenotypic Quality Ontology (PaTO) Gene Ontology Consortiumwww.geneontology.org cellular components, molecular functions, biological processes Gene Ontology (GO) FuGO Working Groupfugo.sf.net design, protocol, data instrumentation, and analysis Functional Genomics Investigation Ontology (FuGO) JLV Mejino Jr., Cornelius Rosse fma.biostr.washington. edu structure of the human body Foundational Model of Anatomy (FMA) Melissa Haendel, Terry Hayamizu, Cornelius Rosse, David Sutherland, (under development) anatomical structures in human and model organisms Common Anatomy Refer- ence Ontology (CARO) Paula Dematos, Rafael Alcantara ebi.ac.uk/chebimolecular entities Chemical Entities of Bio- logical Interest (ChEBI) Jonathan Bard, Michael Ashburner, Oliver Hofman obo.sourceforge.net/cgi- bin/detail.cgi?cell cell types from prokaryotes to mammals Cell Ontology (CL) CustodiansURLScopeOntology

47. 47 Karen Eilbecksong.sf.net properties and features of nucleic sequences Sequence Ontology (SO) RNA Ontology Consortium(under development) three-dimensional RNA structures RNA Ontology (RnaO) Barry Smith, Chris Mungallobo.sf.net/relationshiprelations Relation Ontology (RO) Protein Ontology Consortium(under development) protein types and modifications Protein Ontology (PrO) Michael Ashburner, Suzanna Lewis, Georgios Gkoutos obo.sourceforge.net/cgi -bin/ detail.cgi? attribute_and_value qualities of biomedical entities Phenotypic Quality Ontology (PaTO) Gene Ontology Consortiumwww.geneontology.org cellular components, molecular functions, biological processes Gene Ontology (GO) FuGO Working Groupfugo.sf.net design, protocol, data instrumentation, and analysis Functional Genomics Investigation Ontology (FuGO) JLV Mejino Jr., Cornelius Rosse fma.biostr.washington. edu structure of the human body Foundational Model of Anatomy (FMA) Melissa Haendel, Terry Hayamizu, Cornelius Rosse, David Sutherland, (under development) anatomical structures in human and model organisms Common Anatomy Refer- ence Ontology (CARO) Paula Dematos, Rafael Alcantara ebi.ac.uk/chebimolecular entities Chemical Entities of Bio- logical Interest (ChEBI) Jonathan Bard, Michael Ashburner, Oliver Hofman obo.sourceforge.net/cgi- bin/detail.cgi?cell cell types from prokaryotes to mammals Cell Ontology (CL) CustodiansURLScopeOntology

48. Pleural Cavity Pleural Cavity Interlobar recess Interlobar recess Mesothelium of Pleura Mesothelium of Pleura Pleura(Wall of Sac) Pleura(Wall of Sac) Visceral Pleura Visceral Pleura Pleural Sac Parietal Pleura Parietal Pleura Anatomical Space Organ Cavity Organ Cavity Serous Sac Cavity Serous Sac Cavity Anatomical Structure Anatomical Structure Organ Serous Sac Mediastinal Pleura Mediastinal Pleura Tissue Organ Part Organ Subdivision Organ Subdivision Organ Component Organ Component Organ Cavity Subdivision Organ Cavity Subdivision Serous Sac Cavity Subdivision Serous Sac Cavity Subdivision Foundational Model of Anatomy

49. Pleural Cavity Pleural Cavity Interlobar recess Interlobar recess Mesothelium of Pleura Mesothelium of Pleura Pleura(Wall of Sac) Pleura(Wall of Sac) Visceral Pleura Visceral Pleura Pleural Sac Parietal Pleura Parietal Pleura Anatomical Space Organ Cavity Organ Cavity Serous Sac Cavity Serous Sac Cavity Anatomical Structure Anatomical Structure Organ Serous Sac Mediastinal Pleura Mediastinal Pleura Tissue Organ Part Organ Subdivision Organ Subdivision Organ Component Organ Component Organ Cavity Subdivision Organ Cavity Subdivision Serous Sac Cavity Subdivision Serous Sac Cavity Subdivision part_of is_a

50. 50 Mature OBO Foundry ontologies now undergoing reform Cell Ontology (CL) Chemical Entities of Biological Interest (ChEBI) Foundational Model of Anatomy (FMA) Gene Ontology (GO) Phenotypic Quality Ontology (PaTO) Relation Ontology (RO) Sequence Ontology (SO)

51. 51 Ontologies being built to satisfy Foundry principles ab initio Ontology for Clinical Investigations (OCI) Common Anatomy Reference Ontology (CARO) Ontology for Biomedical Investigations (OBI) Protein Ontology (PRO) RNA Ontology (RnaO) Subcellular Anatomy Ontology (SAO)

52. 52 Ontologies in planning phase Biobank/Biorepository Ontology (BrO, part of OBI) Environment Ontology (EnvO) Immunology Ontology (ImmunO) Infectious Disease Ontology (IDO) Mouse Adult Neurogenesis Ontology (MANGO)

53. OBO Foundry Success Story Model organism research seeks results valuable for the understanding of human disease. This requires the ability to make reliable cross- species comparisons, and for this anatomy is crucial. But different MOD communities have developed their anatomy ontologies in uncoordinated fashion. 53

54. Ontologies facilitate grouping of annotations brain 20 hindbrain 15 rhombomere 10 Query brain without ontology 20 Query brain with ontology 45 54

55. CARO – Common Anatomy Reference Ontology for the first time provides guidelines for model organism researchers who wish to achieve comparability of annotations for the first time provides guidelines for those new to ontology work See Haendel et al., “CARO: The Common Anatomy Reference Ontology”, in: Burger (ed.), Anatomy Ontologies for Bioinformatics: Springer, in press. 55

56. 56 CARO-conformant ontologies already in development: Fish Multi-Species Anatomy Ontology (NSF funding received) Ixodidae and Argasidae (Tick) Anatomy Ontology Mosquito Anatomy Ontology (MAO) Spider Anatomy Ontology Xenopus Anatomy Ontology (XAO) undergoing reform: Drosophila and Zebrafish Anatomy Ontologies

57. Part 3 The Hole Story

58. The Ontology of Environments

59. Initial hypothesis: Environments are holes

61. environment place site niche habitat setting hole spatial region interior location

62. Places are holes

66. 66 RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO) No place for environments

67. A Neglected Major Category in Ontologies thus far Things (e.g. organisms) Qualities / Features Functions Processes Environments = that into which organisms (etc.) fit

68. 68 RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO) Environments are holes in which organisms, cells, molecules... can live environments are here

69. 69 RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT POPULATION ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO) environments for populations

71. Environments are holes

72. Double Hole Structure of the Occupied Niche

73. Tenant, medium and retainer the medium of the bear’s niche is a circumscribed body of air medium might be body of water, cytosol, nasal mucosa, epithelium, endocardium, synovial tissue...

74. The Empty Niche

75. Two Types of Boundary

76. Positive and negative parts positive part negative part or hole (made of matter) (not made of matter)

77. Four Basic Niche Types (Niche as generalized hole) 1: a womb; an egg; a house (better: the interior thereof) 2: a snail’s shell; 3: the niche of a pasturing cow; 4: the niche around a circling buzzard (fiat boundary)

78. Types of Niches a pond, a nest, a cave, a hut, an air- conditioned apartment building the history of evolution = history of the development of niches

79. Types of relations for EnvO in on (surface of) surrounds lives_in attaches to realizes occupies (spatial region)...

80. Lexical Semantics the fruit is in the bowl the bird is in the nest the lion is in the cage the pencil is in the cup the fish is in the river the river is in the valley the water is in the lake the car is in the garage the fetus is in the cavity in the uterine lining the colony of whooping crane is in its breeding grounds

81. Double Hole Structure when a tenant leaves its niche the gap left by the tenant is filled immediately by the surrounding medium

82. A hole in the ground Solid physical boundaries at the floor and walls but with a fiat lid: hole

83. Part 4: Not every hole is an environment

85. An environment is a special kind of (generalized) hole but what kind?

86. Elton – niche as role the ‘niche’ of an animal means its place in the biotic environment, its relations to food and enemies. [...] When an ecologist says ‘there goes a badger’ he should include in his thoughts some definite idea of the animal’s place in the community to which it belongs, just as if he had said ‘there goes the vicar’ (Elton 1927, pp. 63f.)

87. G.E. Hutchinson: niche as volume in a functionally defined space the niche = an n-dimensional hyper- volume whose dimensions correspond to resource gradients over which species are distributed

88. G.E. Hutchinson (1957, 1965)

90. Hypervolume niche = a location in an attribute space defined by a specific constellation of environmental variables such as degree of slope, exposure to sunlight, soil fertility, foliage density, salinity...

91. Niche Construction Lewontin: niches normally arise in symbiosis with the activities of organisms or groups of organisms (“ecosystem engineering”); they are not already there, like vacant rooms in a gigantic evolutionary hotel, awaiting organisms who would evolve into them. (The Triple Helix, Gene Organism, Environment)

92. Part Last: Bringing Together the Spatial and Functional Approaches to Environment Ontology The environment is not a location in an attribute space, but it must have features have such location

93. Every environment must have some spatial location The functional niche presupposes the spatial-structural niche Ontology of environment + ontology of associated environmental features

94. J. J. Gibson’s Ecological Psychology The terrestrial environment is [best] described in terms of a medium, substances, and the surfaces that separate them. (Gibson 1979, p. 16)

95. Gibson’s theory of surface layout ‘a sort of applied geometry that is appropriate for the study of perception and behavior’ (1979, p. 33) ground, open environment, enclosure, detached object, attached object, hollow object, place, sheet, fissure, stick, fiber, dihedral, etc.

96. Gibson’s theory of surface layout as an anatomy of environments systems of barriers, doors, pathways to which the behavior of organisms is specifically attuned, temperature gradients, patterns of movement of air or water molecules water holes, food sources (features) apertures (mouths, sphincters...)

97. Two sets of issues Environments, as spatial structures, and their parts Environmental attributes (qualities, functions), determining multidimensional loci à la Hutchinson

98. Aim To define structural properties such as: open, closed, connected, compact, spatial coincidence, integrity, aggregate, boundary RCC (Region Connection Calculus) plus extensions

99. Ecological Niche Concepts niche as particular place or subdivision of an environment that an organism or population occupies vs. niche as function of an organism or population within an ecological community

100. Next steps Our data needs are to link niche features with geo-locations

101. Scale: From geographic to microbiological From locations of organisms/samples, sources of museum artifacts... to organism interactions, e.g. on bacterial infection – how the interior of one organism or organism part serves as environment for another organism

102. Hosts for bacterial infection (interior of) lung blood (bacteremia) erythrocyte - plasmodium inhabits red blood cells hepatocyte – plasmodium infects liver cells macrophage gut and oral mucosa, nasal mucosa, vaginal mucosa kidney bladder portion of epithelial tissue

104. C: bacteria (arrows) adhering to and penetrating the epithelial cells (×3,000) D: abscess (Ab) formation in subepithelial region with a colony of bacteria (arrows) and a red blood cell (RBC) in it (×2,000)

106. 106 RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO) Environments, environment parts (features), environment qualities

107. Ontologies needed Environment -- Taxonomy place, habitat, city, farm, building (interior), oral cavity, uterine cavity, gut... Environment part – Anatomy of environments (Surface, conduit, entry...) city wall, uterine wall, water source,... Environment function protection, supply of food,... Environment quality – (Phenotypes) ambient temperature, salinity,...