ifomis.org 1 Ontology and Its Applications II Barry Smith

ifomis.org 2 DNA Protein Organelle Cell Tissue Organ Organism m m Scales of anatomy m

ifomis.org 3 Complexity of biological structures 30,000 genes in human 200,000 proteins 100s of cell types 100,000s of disease types 1,000,000s of biochemical pathways (including disease pathways)

ifomis.org 4 New Golden Age of Classification importance of chemistry molecules molecular structures molecular processes

ifomis.org 5 But: each (clinical, pathological, genetic, proteomic, pharmacological …) information system uses its own classification system How can we overcome the incompatibilities which become apparent when data from distinct sources is combined?

ifomis.org 6 Fragment of UMLS SN

ifomis.org 7 IFOMIS idea: move from associative relations between meanings to strictly defined relations between the entities themselves

ifomis.org 8 supplement associative (statistical) datamining with: better data better annotations (link to EHR) better integration more powerful logical reasoning

ifomis.org 9 Key idea To define ontological relations like part_of, develops_from not enough to look just at universals / types: we need also to take account of instances and time (= link to Electronic Health Record)

ifomis.org 10 Kinds of relations : is_a, part_of,... : this explosion instance_of the universal explosion : Mary’s heart part_of Mary

ifomis.org 11 part_of for universals A part_of B =def. given any instance a of A there is some instance b of B such that a instance-level part_of b

ifomis.org 12 Instance-level relations part_of is_located_at has_participant has_agent earlier...

ifomis.org 13 Taking the instance-level part_of as primitive we can define: C 1 part_of C 2 means: any instance of C 1 is part_of some instance of C 2 nucleus part_of cell but not: testis part_of human

ifomis.org 14 from C 1 part_of C 2 we cannot infer that C 2 has_part C 1 human_testis part_of human but not human has_part human testis running has_part breathing but not breathing part_of running

ifomis.org 15 C c at t c at t 1 C 1 transformation_of

ifomis.org 16 child transformation_of fetus adult transformation_of child mature RNA transformation_of pre-RNA

ifomis.org 17 transformation_of fetus transformation_of embryo adult transformation_of child C 2 transformation_of C 1 =def. any instance of C 2 was at some earlier time an instance of C 1

ifomis.org 18 transformation_of c at t 1 C c at t C 1 time same instance pre-RNA  mature RNA child  adult

ifomis.org 19 transformation_of C 2 transformation_of C 1 =def. any instance of C 2 was at some earlier time an instance of C 1

ifomis.org 20 C c at t c at t 1 C 1 embryological development

ifomis.org 21 C c at t c at t 1 C 1 tumor development

ifomis.org 22 Derives_from c derives_from c 1 =def c and c 1 are non- identical and exist in continuous succession

ifomis.org 23 the new component detaches itself from the initial component, which itself continues to exist C c at t C c at t C 1 c 1 at t 1 c at t 1 C 1 c 1 at t the initial component ceases to exist with the formation of the new component

ifomis.org 24 two initial components fuse to form a new component C c at t C 1 c 1 at t 1 C' c' at t

ifomis.org 25 C c at t C 1 c 1 at t 1 C' c' at t derives_from (ovum, sperm  zygote... ) time instances

ifomis.org 26 neuron derives_from neuroblast muscle cell derives_from myoblast child derives_from adult embryo derives_from ovum embryo derives_from sperm corpse derives_from human

ifomis.org 27 The Granularity Gulf most existing data-sources are of fixed, single granularity many (all?) clinical phenomena cross granularities

ifomis.org 28 Universe/Periodic Table clinical space molecule space

ifomis.org 29 part_of adjacent_to contained_in has_participant contained_in intragranular arcs

ifomis.org 30 part_of transgranular arcs

ifomis.org 31 transformation_of C c at t c at t 1 C 1

ifomis.org 32 time & granularity C c at t c at t 1 C 1 transformation

ifomis.org 33 better data (more reliable coding) link to real world via time and instances better integration of ontologies more powerful tools for logical reasoning Standardized formal ontology yields:

ifomis.org 34 and help us to integrate information on the different levels of molecule, cell, organ, person, population and so create synergy between medical informatics and bioinformatics at all levels of granularity

ifomis.org 35

ifomis.org 36 A Theory of Granular Partitions cf. Roland Omnès Understanding Quantum Mechanics mereology, granularity, vagueness formal theory at: vagueness.html

ifomis.org 37 A Simple Partition

ifomis.org 38

ifomis.org 39

ifomis.org 40 A partition can be more or less refined

ifomis.org 41 Coarse-grained Partition

ifomis.org 42 Fine-Grained Partition

ifomis.org 43 mereology-based ontological zooming

ifomis.org 44 Universe/Periodic Table animal bird canary ostrich fish folk biology partition of DNA space

ifomis.org 45 Universe/Periodic Table animal bird canary ostrich fish both are transparent partitions of one and the same reality

ifomis.org 46 Perspectivalism Different partitions may represent cuts through the same reality which are skew to each other

ifomis.org 47 An organism is a totality of molecules An organism is a totality of cells An organism is a single unitary substance... all of these express veridical partitions An organism is a totality of atoms

ifomis.org 48 all express partitions which are transparent, at different levels of granularity, to the same reality beyond

ifomis.org 49 Ontology like cartography must work with maps at different scales and with maps picking out different dimensions of invariants

ifomis.org 50 If ontological realism is right then there are very many map-like partitions, at different scales, which are all transparent to the reality beyond the mistake arises when one supposes that only one of these partitions is veridical

ifomis.org 51 There are not only map-like partitions of reality into spatial chunks but also distinct partitions of reality into universals (genera, categories, kinds, types) mutually compatible ways of providing inventories of universals (among proteins, among cells, among organisms …)

ifomis.org 52 Varieties of granular partitions Partonomies: inventories of the parts of individual entities Maps: partonomies of space Taxonomies: inventories of the universals covering a given domain of reality

ifomis.org 53 Partition Definition: A partition is the drawing of a (typically complex) fiat boundary over a certain domain

ifomis.org 54 GrGr

ifomis.org 55 Partitions are artefacts of our cognition = of our referring, perceiving, classifying, mapping activity

ifomis.org 56 A partition is transparent It leaves the world exactly as it is

ifomis.org 57 Artist’s Grid

ifomis.org 58 Label/Address System A partition typically comes with labels and/or an address system

ifomis.org 59 Mouse Chromosome Five

ifomis.org 60 A partition can comprehend the whole of reality

ifomis.org 61 Universe

ifomis.org 62 It can do this in different ways

ifomis.org 63 The Spinoza Partition

ifomis.org 64 Periodic Table

ifomis.org 65 Partitions have different granularity Maps have different scales Partitions are, roughly, what AI people call ‘ontologies’ (but in which granularity is taken seriously)

ifomis.org 66 Partitions can have empty cells

ifomis.org … Partition of people in this room according to: number of years spent in jail

ifomis.org 68 Partition of people in this room according to: number of days spent in jail

ifomis.org 69 The Parable of the Two Tables from Arthur Eddington, The Nature of the Physical World (1928) Table No. 1 = the ordinary solid table made of wood Table No. 2 = the scientific table

ifomis.org 70 The Parable of the Two Tables ‘My scientific table is mostly emptiness. Sparsely scattered in that emptiness are numerous electric charges rushing about with great speed; but their combined bulk amounts to less than a billionth of the bulk of the table itself.’

ifomis.org 71 Eddington: Only the scientific table exists.

ifomis.org 72 The Parable of the Two Tables Both of the tables exist – in the same place: they are pictured in maps of different scale

ifomis.org 73 Partitions can sometimes create objects fiat objects = objects determined by partitions

ifomis.org 74 = objects which exist independently of our partitions (objects with bona fide boundaries) bona fide objects

ifomis.org 75 Mixed Partitions

ifomis.org 76 Cerebral Cortex

ifomis.org 77 Reciprocal partitions

ifomis.org 78 California Land Cover Reciprocal partitions

ifomis.org Counting requires partitions

ifomis.org 80 Frege: “Numbers belong to the realm of concepts” Smith: Numbers belong to the realm of partitions

ifomis.org 81 Measurement belongs to the realm of partitions   0 0   massively increased... normal increased chronic...

ifomis.org 82 Sets belong to the realm of partitions Sets are not objects in reality, but mathematical tools for talking about reality

ifomis.org 83 Another mistake:

ifomis.org 84 The correct view set-like structures belong here

ifomis.org 85 Set as List Partition A set is a list partition (a set is, roughly, a partition minus labels and address system) The elements exist within the set without order or location —they can be permuted at will and the set remains identical

ifomis.org 86 Partitions do not care Our ordinary judgments in spite of being vague have determinate truth-values because the partitions they impose upon reality do not care about small (e.g. molecule-sized, quantum- sized) differences

ifomis.org 87

ifomis.org 88 What does “Functional” mean in expressions like “Functional Genomics” ?

ifomis.org 89 Towards a Tri-Categorial Ontology of Structures, Functions and Processes = Independent Continuants Dependent Continuants Occurrents

ifomis.org 90 Definition of Function in UMLS Semantic Network Functional Concept = df A concept which is of interest because it pertains to the carrying out of a process or activity. Function  Functional Concept Function  Realization of a Function

ifomis.org 91 What do the kidneys do? Your entire blood volume flows through your kidneys every few minutes, leaving behind excess water, solutes and waste materials The Kidney From Andrew Lonie, University of Melbourne

ifomis.org 92 How does a kidney work? Essentially a massively parallel filter composed of 10 5 to 10 6 nephrons The nephron is the functional unit of the kidney Each nephron is a very convoluted, long, thin tube lined with biochemical pumps

ifomis.org 93 Nephron Functions 10 functional segments 15 different cell types

ifomis.org 94 UMLS Semantic Network entity event physical conceptual object entity organism

ifomis.org 95 RUMLS Semantic Network endurant event structures functions processes

ifomis.org 96 GO’s three disjoint term hierarchies the cellular component (structure) ontology, e.g. flagellum, chromosome, cell the biological process ontology, e.g. glycolysis, death the molecular function ontology, e.g. ice nucleation, binding, protein stabilization

ifomis.org 97 RUMLS Semantic Network endurant event structures functions processes

ifomis.org 98 Functional Genomics What does “Functional“ mean?

ifomis.org 99 The Problem The tumor developed in John’s lung over 25 years

ifomis.org 100 The Problem ____ developed in _____ over 25 years process

ifomis.org 101 The Problem The tumor developed in the lung over 25 years substances things objects continuants

ifomis.org 102 The Problem The tumor developed in John’s lung over 25 years PARTHOOD NOT DETERMINATE

ifomis.org 103 The Problem The tumor developed in the lung over 25 years substances GLUING THESE TOGETHER YIELDS ONTOLOGICAL MONSTERS processes

ifomis.org 104 Substances and processes exist in time in different ways substance t i m e process

ifomis.org 105 SNAP vs SPAN Endurants vs perdurants Continuants vs occurrents In preparing an inventory of reality we keep track of these two different kinds of entities in two different ways

ifomis.org 106 Fourdimensionalism – only processes exist – time is just another dimension, analogous to the three spatial dimensions – substances are analyzed away as worms/fibers within the four-dimensional plenum

ifomis.org 107 There are no substances Bill Clinton does not exist Rather: there exists within the four- dimensional plenum a continuous succession of processes which are similar in a Billclintonizing way

ifomis.org 108 Fourdimensionalism (the SPAN perspective) is right in everything it says But incomplete

ifomis.org 109 Need for Two Orthogonal, Complementary Perspectives SNAP and SPAN

ifomis.org 110 Basic opposition SNAP vs. SPAN objects vs. processes continuants vs. occurrents = Two different ways of existing in time (enduring, or unfolding phase-by-phase)

ifomis.org 111 Three kinds of SNAP entities 1.SNAP Independent: Substances, Objects, Things 2.SNAP Dependent: Qualities, Functions, Conditions, Roles 3.SNAP Spatial regions

ifomis.org 112 SNAP: Entities existing in toto at a time

ifomis.org 113 SNAP-Independent

ifomis.org 114 SNAP Dependent

ifomis.org 115 SPAN: Entities occurring in time

ifomis.org 116 SPAN Dependent (Processes)

ifomis.org 117 SPAN Spatiotemporal Regions

ifomis.org 118 Snapshot Video ontology ontology substance t i m e process

ifomis.org 119 SNAP and SPAN stocks and flows commodities and services product and process anatomy and physiology

ifomis.org 120 SNAP and SPAN SNAP entities - have continuous existence in time - preserve their identity through change - exist in toto if they exist at all SPAN entities - have temporal parts - unfold themselves phase by phase - exist only in their phases/stages

ifomis.org 121 You are a substance Your life is a process You are 3-dimensional Your life is 4-dimensional

ifomis.org 122 Many SNAP Ontologies t1t1 t3t3 t2t2 here time exists outside the ontology, as an index or time-stamp

ifomis.org 123 each SNAP i section through reality includes everything which exists (present tense)

ifomis.org 124 mereology works without restriction (parthood is everywhere determinate) in every SNAP i ontology

ifomis.org 125 SNAP dependent entities States, powers, qualities, functions, dispositions, plans, shapes, liabilities, propensities…

ifomis.org 126 SNAP dependent entities: one-place: your temperature, color, height my knowledge of French the whiteness of this cheese the warmth of this stone the fragility of this glass

ifomis.org 127 relational SNAP dependent entities John Mary love stand in relations of one-sided dependence to a plurality of substances simultaneously one-sided dependence

ifomis.org 128 Spatial regions + sites (contexts, niches, environments) Organism species evolve into environments Domesticated spatial regions: rooms, nostrils, your alimentary tract Fiat spatial regions: JFK designated airspace

ifomis.org 129 here time exists as part of the domain of the ontology The SPAN ontology

ifomis.org 130 mereology works without restriction everywhere here t i m e clinical trial

ifomis.org 131 mereology works without restriction everywhere here t i m e course of a disease

ifomis.org 132 Relational processes kissings, thumpings, conversations, dancings, promisings, infectings, bindings join their carriers together into collectives of greater or lesser duration

ifomis.org 133 problem cases forest fire hurricane Maria traffic jam ocean wave disease anthrax epidemic

ifomis.org 134 forest fire: a process a pack of monkeys jumping from tree to tree and eating up the trees as they go the Olympic flame: a process or a thing? (anthrax spores are little monkeys)

ifomis.org 135 A disease The course/history of a disease

ifomis.org 136 The Epidemic (SNAP) The Spread of an Epidemic (SPAN)

ifomis.org 137 SNAP dependent entities plan function role disposition disease therapy SNAP

ifomis.org 138 Realization (SNAP  SPAN) execution of a plan expression of a function exercise of a role realization of a disposition course of a disease

ifomis.org 139 SNAP dependent entities and their SPAN realizations execution expression exercise realization course application SPAN

ifomis.org 140 More examples: performance of a symphony expression of an emotion change of body temperature spreading of an epidemic application of a therapy

ifomis.org 141 The Tri-Categorial Ontology SNAP SPAN structures functions processes = independent = dependent continants continuants

ifomis.org 142 The Tri-Categorial Ontology continuants occurrents structures functions processes = independent = dependent continants continuants

ifomis.org 143 A Window on Reality continuants occurrents structures functions processes = independent = dependent continants continuants Entities in all three categories exist both as universals and as instances (as tokens and as types)

ifomis.org 144 Realism about Functions (Biological) Functions existed for many millions of years before there were cognitive agents Hence a cognitive imputation-based theory of functions à la Prof. Mizoguchi cannot be correct

ifomis.org 145 Two distinct instances The function of your heart is: to pump blood The function of my heart is: to pump blood instantiating the same universal

ifomis.org 146 Functions have bearers The bearer of the function of your heart is: your heart. Functions are dependent continuants. The bearers of functions are independent continuants (hearts, screwdrivers …)

ifomis.org 147 Functions are realized in special sorts of processes called functionings

ifomis.org 148 Functions can exist even when they are not being realized

ifomis.org 149 Biological functions are always constituent functions If X has a biological function then there is some organism Y of which X is a part and X’s functioning is in the service of (  for the benefit of) the organism Y The function of your heart is: to pump blood = your heart has the disposition to pump blood in normal circumstances and this is to your benefit

ifomis.org 150 Functions are beneficial If an organism has a constituent part X, and if X is the bearer of a function Z, then those processes which are the realizations of the function Z are (in normal circumstances) beneficial to the organism (  such as to sustain the organism in existence) (  such as to give the organism a normal life for an organism of this type)

ifomis.org 151 Functional Genomics = study of what the genes contribute to the organism in the way of survival (Bad genes do not have functions) Every oncogene is a proto-oncogene There is functioning, poor functioning, malfunctioning There is not having a function at all

ifomis.org 152 Not all bodily processes are functions The pumping of the heart = function The thumping of the heart = by-product Curing headaches = function of aspirin Causing bleeding of the stomach = by- product

ifomis.org 153 Does this sense of ‘function’ correspond to the way biologists talk?

ifomis.org 154 Clinical vs. biological sense of ‘function’ Biologists sometimes talk about biological structures ‘gaining function’ (= being switched on) even where their functioning is not beneficial Clinical medicine = all functions associated with malfunctionings, which it is the physicians job to put right

ifomis.org 155

ifomis.org 156 Functions 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

ifomis.org 157 Functions are associated with certain characteristic process shapes Screwdriver: rotates and simultaneously moves forward simultaneously transferring torque from hand and arm to screw Heart: performs a contracting movement inwards and an expanding movement outwards simultaneously transferring hydraulic pressure to the blood stored within its chambers

ifomis.org 158 For each function there is an associated family of (four- dimensional) process shapes, organized around a core of prototypical process shapes representing good functioning The prototypes play a role analogous to the standard meter rule in the organization of those one-dimensional shapes we call lengths

ifomis.org 159

ifomis.org 160 Outside the core are process shapes which are not instances of functioning at all

ifomis.org 161

ifomis.org 162

ifomis.org 163 Normal functioning = functioning (realizing a four-dimensional shape) at or close to the prototype

ifomis.org 164 Prototypes good functioning

ifomis.org 165 Prototypes reasonable functioning

ifomis.org 166 Poor functioning poor functioning

ifomis.org 167 Malfunctioning malfunctioning

ifomis.org 168 Death? not functioning at all

ifomis.org 169 Not functioning at all = death modulo: criticality of the system involved

ifomis.org 170 Bodily Systems respiratory digestive skeletal circulatory musculatory immune

ifomis.org 171

ifomis.org 172 The End

ifomis.org 173

ifomis.org 174 E N D E