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

3. 2 Problem of ensuring sensible cooperation in a massively interdisciplinary community concept type class instance model representation data

4. 3 Part 1: What is an Ontology?

5. 4 what cellular component? what molecular function? what biological process?

6. 5 natural language labels designed for use in annotations to make the data cognitively accessible to human beings and algorithmically tractable to computers

7. 6 compare: legends for maps

8. 7 common legends allow (cross-border) integration

9. 8 ontologies are legends for data

10. 9 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. 11 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. 15 names of types

17. 16 names of instances

18. 17 A basic distinction type vs. instance science text vs. diary human being vs. Michael Ashburner

19. 18 A515287DC3300 Dust Collector Fan B521683Gilmer Belt C521682Motor Drive Belt Catalog vs. inventory

20. 19 Ontology types Instances

21. 20 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 21

23. 22 types vs. their extensions type {a,b,c,...} class of instances = a collections of particulars

24. 23 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. 24 types vs. classes types {c,d,e,...} classes

26. 25 types vs. classes types extensions ~ defined classes

27. 26 Defined class =def a class defined by a general term which does not designate a type diabetic patient in Leipzig sibling of Finnish spy member of Abba aged > 50 years pizza with > 4 different toppings red wine to serve with fish

28. 27 Part 2: The OBO Foundry?

29. 28 what cellular component? what molecular function? what biological process?

30. The Gene Ontology

32. 31 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. 32 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. 34 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. 36  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. 37  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. 38  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. 39 Formal-Ontological Relations is_a part_of located_at depends_on is_boundary_of adjacent_to

41. 40 To support integration of ontologies relational expressions such as is_a part_of... should be used in the same way in all ontologies involved

42. 41 to define these relations properly we need to take account of both types and instances in reality

43. 42 Kinds of relations : Toronto instance_of city : Toronto part_of Ontario : waterfall part_of river

44. 43 is_a human is_a mammal all instances of the type human are as a matter of necessity instances of the type mammal

45. 44 part_of For instances part_of = instance-level parthood (for example between Mary and her heart) For types A part_of B =def. given any instance a of A there is some instance b of B such that a part_of b

46. 45 instance-level relations part_of is_located_at has_participant has_agent earlier occupies...

47. 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

48. 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

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 Foundational Model of Anatomy

50. 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

51. 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)

52. 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)

53. 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)

54. 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

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

56. 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

57. 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

58. Part 3 The Hole Story

59. The Ontology of Environments

60. Initial hypothesis: Environments are holes

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

63. Places are holes

68. 67 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

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

70. 69 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

71. 70 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

73. Environments are holes

74. Double Hole Structure of the Occupied Niche

75. 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...

76. The Empty Niche

77. Two Types of Boundary

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

79. 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)

80. 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

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

82. 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

83. Niches on different levels of the food chain a. at the bottom of the hiearchy is the saprophytic chain, in which micro-organisms live on dead organic matter; b. above this is the primary relation between animals and the plants they consume; c. above this is the predator chain, in which animals of one sort eat smaller animals of another sort; d. crosscutting all of these is the parasite chain, in which a smaller organism consumes part of a larger host organism.

84. Apertures, Mouths, and Sphincters security vs. freedom of movement plants barnacles and snails fish and birds skin or hide

85. Security vs. Freedom the mouth of the bear, the threshold of your office freedom of movement and fiat boundaries (of niches and of organisms) the alimentary canal: hole or part ?

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

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

88. The Medium for Life a medium is a medium only relative to a given type of niche a medium requires either a retainer (in the case of a vacant niche) or a tenant (in the case of an occupied niche) Michelangelo’s David examples of media: air, smoke, water

89. Mixed Media mixed media (including radioactive impurities, as well as as vitamins, amino acids, salts, and sugars) Scrooge, crowds, plastic balls every medium is maximal what does the job of filling out the niche whose medium is made of air or water? Answer: bodies of vacuum

90. Extending Mereology mereology, formalized in terms of the single primitive relation: part of mereotopology, obtained by adding extra primitive relation boundary for theory of location, obtained by adding extra primitive relation located at formal ecology, obtained by adding extra primitive relation niche for

91. Holes involve two kinds of boundaries bona fide boundaries which exist independently of our demarcating acts fiat boundaries which exist only because we put them there

92. and some holes can move

93. Where are Places? Concrete Entity [Exists in Space and Time] Entity in 3-D Ontology [Endure. No Temporal Parts] Spatial Region of Dimension 0,1,2,3 Dependent Entity Quality (Your Redness, My Tallness) [Form Quality Regions/Scales] Quasi-Quality Prices, Values, Obligations Role, Function, Power Have realizations (called: Processes) Quasi-Role/Function/Power The Functions of the President Independent Entity Substance [maximally connected causal unity] Aggregate of Substances * (includes masses of stuff? liquids?) Fiat Part of Substance * Nose, Ear, Mountain Boundary of Substance * Fiat or Bona Fide or Mixed Quasi-Substance Church, College, Corporation Entity in 4-D Ontology [Perdure. Unfold in Time] Processual Entity Process [Has Unity] Clinical trial; exercise of role Aggregate of Processes* Fiat Part of Process* Instantaneous Temporal Boundary of Process (= Ingarden’s 'Event’)* Quasi-Process John’s Youth. John’s Life Spatio-Temporal Region Dim = T, T+0, T+1, T+2, T+3

94. Where are Places (Holes)? Concrete Entity [Exists in Space and Time] Entity in 3-D Ontology [Endure. No Temporal Parts] Spatial Region of Dimension 0,1,2,3 Dependent Entity Quality (Your Redness, My Tallness) [Form Quality Regions/Scales] Quasi-Quality Prices, Values, Obligations Role, Function, Power Have realizations (called: Processes) Quasi-Role/Function/Power The Functions of the President Independent Entity Substance [maximally connected causal unity] Aggregate of Substances * (includes masses of stuff? liquids?) Fiat Part of Substance * Nose, Ear, Mountain Boundary of Substance * Fiat or Bona Fide or Mixed Quasi-Substance Church, College, Corporation Entity in 4-D Ontology [Perdure. Unfold in Time] Processual Entity Process [Has Unity] Clinical trial; exercise of role Aggregate of Processes* Fiat Part of Process* Instantaneous Temporal Boundary of Process (= Ingarden’s 'Event’)* Quasi-Process John’s Youth. John’s Life Spatio-Temporal Region Dim = T, T+0, T+1, T+2, T+3

95. Where are Places? Concrete Entity [Exists in Space and Time] Entity in 3-D Ontology [Endure. No Temporal Parts] Spatial Region of Dimension 0,1,2,3 Dependent Entity Independent Entity Entity in 4-D Ontology [Perdure. Unfold in Time] Processual Entity Spatio-Temporal Region Dim = T, T+0, T+1, T+2, T+3

96. Types of Places Concrete Entity [Exists in Space and Time] Entity in 3-D Ontology [Endure. No Temporal Parts] Generalized Spatial Region of Dimension 0,1,2,3 Stationary Mobile Dependent Entity Independent Entity Entity in 4-D Ontology [Perdure. Unfold in Time] Processual Entity Spatio-Temporal Region Dim = T, T+0, T+1, T+2, T+3

98. Armchair Ontology

99. artefacts and niches

100. Part 4: Not every hole is an environment

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

102. 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.)

103. 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

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

106. 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...

107. 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)

108. 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

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

110. 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)

111. Affordances “The affordances of the environment are what it offers the animal, what it provides or furnishes, either for good or evil.” James J. Gibson, The Ecological Approach to Visual Perception

112. Affordances “The verb to afford is found in the dictionary, but affordance is not. I have made it up.” “I mean by it something that refers both to the animal and the environment in a way that no existing term does.” (p. 127)

113. 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.

114. 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...)

115. security vs. freedom of movement plants barnacles and snails fish and birds skin or hide

116. environment place niche habitat setting hole spatial region interior

117. Marks of (bodily) substance i.Rounded-offness ii.Occupies space iii.Complete boundary iv.May have substantial parts (nesting) v.May be included in larger substances vi.Has a life (manifests contrary accidents at different times)

118. Marks of Niches (i)A niche enjoys a certain natural completeness or rounded-offness, being neither too small nor too large —in contrast to the arbitrary undetached parts of environmental settings and to arbitrary heaps or aggregates of environmental settings.

119. (ii) A niche takes up space, it occupies a physical-temporal locale, and is such as to have spatial parts. Within this physical-temporal locale is a privileged locus—a hole— into which the tenant or occupant of the setting fits exactly.

120. (iii) A niche has an outer boundary: there are objects which fall clearly within it, and other objects which fall clearly outside it. (The boundary itself need not be crisp.)

121. (iv) An environmental setting may have actual parts which are also environmental settings.

122. (v) An environmental setting may similarly be a proper part of larger, circumcluding environmental settings.

123. (vi) Niche has a life is now warm, now cold now at peace, now at war ….

124. Marks of (bodily) substance i.Rounded-offness ii.Occupies space iii.Complete boundary iv.May have substantial parts (nesting) v.May be included in larger substances vi.Has a life; is now warm, now cold

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

126. Environments plus environmental features food resources predators prey climate skin, hide...

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

128. 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

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

130. 129 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

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

132. 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

134. 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)

136. 135 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

137. Ontologies needed Environment -- Taxonomy place, habitat, city, oral cavity, uterine cavity... 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,...