1. switch on Webex

2. Examples of new ontologies using BFO Actionable Intelligence Retrieval System (AIRS) US Transcom (Transportation Command) Enterprise Ontology (http://www.securboration.com/)http://www.securboration.com/ Mental Functioning Ontology (MFO), Emotion Ontology (MFO-EM) Financial Report Ontology: FRO – here BFO (and IAO) must be under the hood

3. FMA: BFO under the hood

4. Blue Force Overwatch The Plant Ontology

5. cROP: Common Reference Ontologies for Plants

6. Role of BFO in OBO Foundry OBO Foundry and related suites of ontologies will work only if their component ontologies are orthogonal Orthogonality can be established only if these ontologies are comparable BFO is at the core of the strategy to ensure compatibility

7. id: HP:0001943 ! Hypoglycemia = = decreased concentration of glucose in the blood intersection_of: PATO:0001163 ! decreased concentration intersection_of: qualifier PATO:0000460 ! abnormal intersection_of: towards CHEBI:17234 ! glucose intersection_of: inheres_in FMA:9670 ! Portion of blood Class: Hypoglycemia ≡ decreased concentration & towards some glucose & inheres_in some portion of blood & qualifier some 'abnormal‘ P. Robinson: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224779/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224779/ http://www.ncbi.nlm.nih.gov/pubmed/23104991

8. HP:0001720 ! tachycardia Process: GO:0060048 cardiac muscle contraction Quality: PATO:0000912 increased rate PATO:Rate =def. A quality of a single process inhering in a bearer by virtue of the bearer's occurrence per unit time logically: rate(r,p) =def. p is a process & p consists of a sequence of similar sub-processes & these sub-processes repeat r times per unit time Note that there is no reference to a quality or to inherence here

9. Tachycardi Thus Tachycardia only exists if there is the sort of cyclical repetition of cardiac muscle contraction that is involved in the heart's beating. Thus Tachycardia is not a rate of cardiac muscle contraction, but rather a rate of cardiac muscle contraction repetition.

10. Treatment of ‘process qualities’ ‘BFO:quality’ just means: a quality of an independent continuant PATO:process-quality uses 'quality' in a different sense; providing this sense is well- defined, there is no objection to its use. Unfortunately most PATO:process-quality terms are currently poorly defined. The hope is that use of BFO 2.0 can help to bring improvements.

11. rate (rough version) rate(r,p) =def. p is a process & p consists of a sequence of similar sub-processes & these sub-processes repeat r times per unit time increased-rate(r,p) = def. p is such that r is greater than a certain normal threshold (defined for each particular kind of patient) There are numbers here, and time units, and thresholds for numbers.

12. But there are no extra entities called ‘process qualities’ If we observe that there are 3 apples in a bowl on Wednesday and 2 apples in the same bowl on Thursday, then we could express this by saying that the apples in the bowl had the quality of threeness on Wednesday and the quality of twoness on Thursday. People could talk like that if they wanted, but it would be ontologically much less adequate than just the assertion underlined above.

13. Similarly, if we observe that there is a 63 bpm heart rate in a patient on Wednesday and 102 bpm heart rate in the same partient on Thursday, then we could express this by saying that the heart beat process of the patient had the quality of sixtythree-bpm-ness on Wednesday and of onehundredandtwo-bpm-ness on Thursday. People could talk like that if they wanted, but it would be ontologically much less adequate than just the assertion underlined above/ 63bpm Wednesday and 102 bpm in the same patient on Thursday i.e. more beats per minute on Thursday

14. What BFO is designed to do BFO is not intending to constrain what people say, merely to provide a formally coherent basis for definitions (for example in PATO). Given this basis, it should be possible to define all the terms one needs, including all the terms one needs from PATO.

15. Which general terms refer to universals? For some general terms X we can formulate definitions of the following sort: (C) Collection of X’s =def. collection of particulars of type X. How do we determine whether for (C) holds of a given term ‘X’? This is the job of scientists, in an on-going process of terminology evolution through which those terms come to be selected for that are fit to serve in successive formulations of the corresponding scientific theory.

16. Which general terms refer to universals? Each scientific theory as it exists at any given stage will likely be marked by (as yet unidentified) terminologically relevant errors, and these errors will accordingly be carried over into the corresponding ontology. Hence, we cannot embrace any one-one correspondence between scientific general terms and universals in reality. Rather, we should assume, for heuristic purposes only, that at any given stage the terms used by scientists in a given discipline refer to universals, knowing full well that this assumption may be false for any given term.

17. Qualities determinable and determinate temperature blood pressure mass... are continuants they exist through time while undergoing changes 17

18. Qualities temperature / blood pressure / mass... are dimensions of variation within the structure of the entity; a quality is something which can change while its bearer remains one and the same 18

19. A Chart representing how John’s temperature changes 19

20. Qualities temperature / blood pressure / mass... are dimensions of variation within the structure of the entity; a quality is something which can change while its bearer remains one and the same hence only independent continuants may have qualities 20

21. John’s temperature the temperature John has throughout his entire life, cycles through different determinate temperatures from one time to the next John’s temperature is a physiology variable which, in thus changing, exerts an influence on other physiology variables through time 21

22. temperature John’s temperature 22 37ºC37.1ºC37.5ºC37.2ºC37.3ºC37.4ºC instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6

23. One issue Chris Mungall: BFO should have some documented position as to determinables are still present when their value is zero OR physics is such that no true determinable can take on a zero value.

24. a quality is something which can change while its bearer remains one and the same hence only independent continuants may have qualities for suppose q were a quality of a process then q would have to be something which could change while the process, its bearer, would remain one and the same – and this is not possible 24

25. temperature course John’s temperature 25 increasing temperature course constant temperature course decreasing temperature course instantiates at t 1 instantiates at t 4 instantiates at t 5

26. temperature John’s temperature 37.2ºC instantiates at t 3 unit of measurement ºC measures information artefact measurement record “John has temperature 37.2ºC at t 3 ” instantiates about uses John inheres_in

27. temperature John’s temperature 37.2ºC temperature instantiates at t 3 unit of measurement ºC measures information artefact measurement record “37.2ºC at t 3 ” instantiates about uses about note re IAO aboutness

28. BFO: The Very Top continuant independent continuant dependent continuant quality occurrent temperature 28

29. Blinding Flash of the Obvious independent continuant dependent continuant quality temperature types instances organism John John’s temperature 29

30. Blinding Flash of the Obvious independent continuant dependent continuant quality temperature types instances organism John John’s temperature 30

31. independent continuant dependent continuant quality temperature types instances organism John John’s temperature 31

32. Can sites have histories? Full process(p) =def. there is some spatiotemporal regions r & p is the sum of all processes occurring in r A history is a full process Participants of a history: independent continuant, site – but what if they coincide spatio-temporally 32

33. Process profiles Full process(p) =def. there is some spatiotemporal regions r & p is the sum of all processes occurring in r Example of full process: history Process profile = a process that is less than a full process 33

34. Canonical example A spinning top is spinning A spinning top is simultaneously warming The spinning and the warming are both proper parts of the full process (= all the processes taking place within the 34

35. Families of process profiles Quality process profiles Measurement/assay process profiles Scientific discipline demarcated process profiles Diseases Speech, music, thinking, writing, dancing … 35

36. Relative process profiles 36

37. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process life of an organism John’s life 37

38. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process course of temperature changes John’s temperature history 38 process profile quality process profile

39. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process life of an organism John’s life 39

40. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process metabolism of an organism John’s metabolism 40 process profile

41. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process growth of an organism John’s growth 41 process profile

42. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process development of an organism John’s development 42 process profile

43. temperature John’s temperature 43 37ºC37.1ºC37.5ºC37.2ºC37.3ºC37.4ºC instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6

44. human John embryofetusadultneonateinfantchild instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6

45. human John 45 embryofetusadultneonateinfantchild instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6 in nature, no sharp boundaries here

46. portion of water this portion of H 2 0 46 portion of ice portion of liquid water portion of gas instantiates at t 1 instantiates at t 2 instantiates at t 3 Phase transitions

47. temperature John’s temperature 47 37ºC37.1ºC37.5ºC37.2ºC37.3ºC37.4ºC instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6 in nature, no sharp boundaries here

48. 48

49. heart disease John’s heart disease (continuant) 49 disease with asymptomatic disease, silent infarction disease with early lesions and small fibrous plaques disease with stable angina disease with surface disruption of plaque disease with unstable angina instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6

50. heart function: to pump John’s heart function: to pump 50 function with asymptomatic disease, silent infarction function with early lesions and small fibrous plaques function with stable angina function with surface disruption of plaque function with unstable angina instantiates at t 1 instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 function with healthy heart instantiates at t 6

51. heart disease John’s heart disease (continuant) 51 disease with asymptomatic disease, silent infarction disease with early lesions and small fibrous plaques disease with stable angina disease with surface disruption of plaque disease with unstable angina instantiates at t 2 instantiates at t 3 instantiates at t 4 instantiates at t 5 instantiates at t 6

52. What is the course of John’s heart disease? 52

53. independent continuant dependent continuant disposition heart disease organism John John’s heart disease occurrent process heart disease course John’s heart disease course 53 process profile

54. physics plus control of the physics what the biological function does is to regulate the physics parameter: rate of cardiac contraction (with range of normality, and abnormality) mathematical function: to pump = mapping between input- and output-pressure the parameters are fixed dispositions are changing the parameter values, 54

55. heart function: to pump John’s heart function: to pump 55 pumping function of heart after fatality instantiates at t 7

56. heart function: to pump John’s heart function: to pump 56 pumping function of healthy heart instantiates at t 1 this portion of deoxygenated blood 1 instantiates at t 1 material entity portion of blood this portion of oxygenated blood instantiates at t 1 material entity portion of blood has inputhas output

57. heart function: to pump John’s heart function: to pump 57 instantiates at t 1 this clot 1 instantiates at t 1 this clot instantiates at t 1 material entity clot has inputhas output pumping function of healthy heart

58. heart function: to pump John’s heart function: to pump 58 pumping function of healthy heart instantiates at t 1 this portion of blood instantiates at t 1 material entity oxygenated portion of blood this concentration instantiates at t 1 quality concentration of oxygen has output need to get time right

59. Continuant Occurrent Independent Continuant Specifically Dependent Continuant Quality Process Generically Dependent Continuant Information Artifact Sequence…

60. GDCs universals are unchangeable -- GDCs are always such that they are changeable (there are instances of the relevant universal which can change, e.g. successive editions of books)

61. lower levels of types do not ‘carry identity’ in OntoClean terms are threshold divisions (hence we do not have sharp boundaries, and we have a certain degree of choice, e.g. in how many subtypes to distinguish, though not in their ordering) 61

62. independent continuant dependent continuant quality temperature types instances organism John John’s temperature 62

63. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process course of temperature changes John’s temperature history 63

64. independent continuant dependent continuant quality temperature organism John John’s temperature occurrent process life of an organism John’s life 64

65. temperature John’s temperature 37.2ºC temperature instantiates at t 3 information artefact measurement datum “37.2ºC at t 3 ” instantiates measurement assay qualityprocess temperature assay at t 3 instantiates has output John has_input about

67. BFO: The Very Top continuant independent continuant dependent continuant 67

68. dependent continuant quality realizable dependent continuant 68 role (optional) disposition (has physical basis)

69. dependent continuant qualityrealizable role (optional) disposition (aka ‘ability’) function (a disposition designed or selected for)

70. :. Role of some chemical compound: to serve as analyte in an experiment of this human being: to serve as PI of this research project 70

71. :. Role optional: exists because the bearer is in some special natural, social, or institutional set of circumstances in which the bearer does not have to be 71

72. :. Roles often form systems of mutual dependence husband / wife first in queue / last in queue doctor / patient host / pathogen 72

73. :. Function - of liver: to store glycogen - of birth canal: to enable transport - of eye: to see - of mitochondrion: to produce ATP reflection of physical makeup of bearer 73

74. :. Qualities are categorical features of reality – you just have them Functions, roles and dispositions are potential featires of reality: they are realizable dependent continuants, realized in certain associated processes 74

75. independent continuant dependent continuant role drug role portion of chemical compound this portion of aspirin role of this portion of aspirin occurrent process process of drug adminstration John’s taking this portion of aspirin 75

76. independent continuant dependent continuant role drug role portion of chemical compound this portion of aspirin role of this portion of aspirin occurrent process process of drug adminstration John’s taking this portion of aspirin 76 inheres_in realized_in

77. The Road to Convergence All ontologies for each given domain (anatomy, chemistry…) should be part of a single suite of interoperable ontologies should use a common top-level core for subdomains with many variants, should follow the strategy of canonical ontologies with extensions should require acceptance of common, tested guidelines on all subscribing ontology developers 77

78. CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Organism-Level Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) Cellular Process (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO) initial OBO Foundry coverage, ontologies automatically semantically coupled GRANULARITY RELATION TO TIME 78

79. Disposition (Internally- Grounded Realizable Entity) disposition =def. a realizable entity which if it ceases to exist, then its bearer is physically changed, and whose realization occurs when this bearer is in some special physical circumstances, in virtue of the bearer’s physical make-up 79

80. Anatomy Ontology (FMA*, CARO) Environment Ontology (EnvO) Infectious Disease Ontology (IDO*) Biological Process Ontology (GO*) Cell Ontology (CL)* Cellular Component Ontology (FMA*, GO*) Phenotypic Quality Ontology (PaTO) Subcellular Anatomy Ontology (SAO) Sequence Ontology (SO*) Molecular Function (GO*) Protein Ontology (PRO*) OBO Foundry Modular Organization top level mid-level domain level Information Artifact Ontology (IAO) Ontology for Biomedical Investigations (OBI) Spatial Ontology (BSPO) Basic Formal Ontology (BFO) 80

81. Relations instance-instance (primitives allow definitions) instance-type type-type RO 2.0 type-type – All-some rule holds add causes dependence includes mutual dependence among roles, functions

82. Keep RO 2.0 small ‘depends_on’ is short for ‘specifically_depends_on’ ‘generically_depends_on’ is written out in full life of has physical basis

83. address relations between site, located_in contained_in

84. RO 2.0 lists simple relations (such as depends_on); there are many complex defined relations (such as inheres_in, is_quality_of) A inheres_of B =def. A depends_on B and A is_a dependent continuant and B is_a independent continuant A is_quality_of B =def. A depends_on B and A is_a quality and B is_a independent continuant

85. starting point is here (Work of Chris Mungall) http://www.fruitfly.org/~cjm/ro/ro.html

86. Generic Dependence Specific Dependence Duration of

87. Get versioning right CL is a standard version

88. keep ‘derives from’ change examples recommend biologists use ‘develops from’ location involves site? vaccine, clinical outcome, effectiveness prevention, diagnosis, treatment, clinical registry  ogms

89. The Relation Ontology immanent relations in BFO – specific dependence – generic dependence – realization 89

90. How to use the RO all–some form LMO2 molecules interact with ELF2 molecules false LMO2 molecules have the disposition to interact with ELF2 molecules true

91. Axioms ALL Occurrent depends_on SOME Continuant ALL DependentContinuant depends_on SOME IndependentContinuant ALL IndependentContinuant occupies SOME 3D SpatialRegion ALL Site occupies SOME 3D SpatialRegion ALL BoundaryOfObject occupies SOME 0, 1 or 2D SpatialRegion 91

92. Axioms ALL BoundaryOfObject is_part_of SOME Object ALL Object has_part SOME BoundaryOfObject ALL ProcessualEntity occurs_in SOME SpatiotemporalRegion ALL ProcessualEntity has_participant SOME IndependentConinuant 92

93. Only something that holds of all As will be an assertion that holds of the type A Hence the All-Some rule Or analogous rules for n-ary relations (where n > 2) 93

94. Definitions of type-level relations presuppose underlying instance-level relations A is_a B presupposes instance_of All instances of A are instances of B A part_of B presupposes instance-level-part-of Every instance of A are instance-level-parts-of some instance of B

95. Rules for including relations in RO To avoid forking, keep RO as small as possible If we have a relation, say, adjacent_to in RO, then we should not add lists of easily defined relations of the form adjacent_to_organ: adjacent_to_cytoplasm: adjacent_to_neuron: In general: include a relation only if it is lexicalized 95

96. Rules for including relations in RO In every case we need to check, before we add a relation A R B, that, for some set of A and B terms we have data about the As and data about the Bs which is such that all the instances of A stand in instance- level R to some B e.g. all the instances of cell membrane stand in instance-level part_of to cell 96

97. Rules for including relations in RO Some_some relations are important not to ontology but to the treatment of empirical data e.g. relating to exceptions to proposed general hypotheses However, in developing RO, we will need to keep track of instance-level relations in any case, and then corresponding some-some relations (and also various kinds of probabilistic relations) come for free 97

98. Thus for example Instead of: results_in_reception_of_stimulus_and_conversion _into_molecular_signal_of use just the relations: results_in, is_a and the types: reception_of_stimulus, conversion_into_molecular_signal 98

99. Or in other words: A results_in_reception_of_stimulus_and_ conversion_into_molecular_signal_of B =Def. A results_in B & B is_a reception_of_stimulus & B is_a conversion_into_molecular_signal 99

100. Consequences of including only all- some relations in RO All relations will be evaluable as 1.Transitive 2.Symmetric 3.Reflexive 4.Anti-Symmetric All relations will support reasoning is_somehow_related_to is the worst kind of relation to create 100

101. True Path Rule the pathway from a child term all the way up to its top-level parent(s) must always be true (Gene Ontology Consortium, 2001) = both is_a and part_of are transitive

102. Lacks Instance-type level p lacks U with respect to r at time t =def. there is no instance u of U such that p stands in r to u at t. Type-type level C1 lacks C2 with respect to r =def. for all c,t, if c instance of C1 at t then c lacks C2 with respect to r at time t. Need a way to state on top of this: that C1s normally stand in r to some C2

103. To be added to the Relation Ontology RO Core (examples) dependent_on (between a dependent entity and its carrier or bearer) quality_of (between a dependent and an independent continuant) functioning_of (between a process and an independent continuant)

104. To be added to the Relation Ontology RO Core (examples) dependent_on (between a dependent entity and its carrier or bearer) quality_of (between a dependent and an independent continuant) functioning_of (between a process and an independent continuant)

105. To be added to the Relation Ontology RO IL (instance-level relations) (examples) lacks (between an instance and a type, e.g. this pig lacks tail) dependent_on (between a dependent entity and its carrier or bearer) quality_of (between a dependent and an independent continuant) functioning_of (between a process and an independent continuant)

106. process has_site a = process has_participant b and b part_of a process has_site alveolar membrane = process has_participant hemoglobin and hemoglobin part_of alvealor membrane process:injection has_site jugular vein = process has participant (some dose of compound in the form of liquid with role drug) and (some dose of compound in the form of liquid with role drug) part_of jugular vein. Why going for such convolution ? What is the gain here ? What is the cost of adding a primitive (when there is a valid case for it) All this is declared at instance level but surely all instances of intrajugular injection must take place in some jugular vein (I am of course talking of canonical injection, not those performed by trainees )

107. dis position =def. a realizable entity which if it ceases to exist, then its bearer is physically changed, and whose realization occurs when this bearer is in some special physical circumstances, in virtue of the bearer’s physical make-up 107

108. function =def. a disposition that is such that the physical make-up of its bearer is something the bearer possesses because it came into being, either through natural [‘positive’?] selection (in the case of natural biological entities) or through intentional design (in the case of artifacts), in order to realize processes of a certain kind.

109. Relation Ontology 2.0

110. RO http://obofoundry.org/ro/ is_a part_of has_part located_in contained_in adjacent_to transformation_of derives_from preceded_by has_participant has_agent Multiple defined relations plus: instance_of, instance-level relations

111. Strategy Small number of relations to be added to this list The whole list to be incorporated into BFO 2.0 Other relations

112. New Proposed Relations specific dependence (between SDC and bearer) generic dependence (between GDC and bearer) concretization of (between SDC and GDC) boundary_of realizes is_about lacks projects_onto (region)

113. Lacks Instance-type level p lacks U with respect to r at time t =def. there is no instance u of U such that p stands in r to u at t. Type-type level C1 lacks C2 with respect to r =def. for all c,t, if c instance of C1 at t then c lacks C2 with respect to r at time t.

114. Defined relations in RO 2.0 a inheres_in b=def. a is specifically dependent on b (a and b are continuants) quality_of =def. a inheres_in b and a is a quality functioning_of (between a process and an independent continuant)

115. To be added to the Relation Ontology RO IL (instance-level relations) (examples) lacks (between an instance and a type, e.g. this pig lacks tail) dependent_on (between a dependent entity and its carrier or bearer) quality_of (between a dependent and an independent continuant) functioning_of (between a process and an independent continuant)

116. How to deal with shapes? Shapes seem to be qualities of spatial regions as well as of independent continuants, but BFO says all qualities are qualities of independent continuants

117. The spatial subdivisions used e.g. in sampling experiments to be dealt with as fiat parts of sites.

118. Clarifications needed Time, duration, time point Spatial extent, distance, gap quality, spatial coordinate: length as quality vs. length of spatial interval