The Pragmatics and Formality of Authoring OntologiesOdsl 2016
- 1. Formality and Pragmatics in Authoring Ontologies Robert Stevens ODLS 2016 School of Computer Science The University of Manchester Manchester United Kingdom M13 9PL Robert.stevens@manchester.ac.uk
- 2. Acknowledgements • On-going work with Phil Lord on normalising the Gene Ontology • The Gene Ontology folk for making GO • Nico Matentzoglu for my slides • Mercedes Casteleiro for numbers
- 3. Formality and Pragmatics • Formality: Acting strictly according to procedure or rules – Ontological formality – Representational formality • Pragmatics: Behaviour driven by practical consequences rather than dogma • There’s a tension between the two
- 4. Gene Ontology Molecular Function • D-alanyl carrier activity • acetylcholine receptor regulator activity • antioxidant activity • binding • calcium channel regulator activity • catalytic activity • channel regulator activity • chemoattractant activity • chemorepellent activity • core DNA-dependent RNA polymerase binding promoter specificity activity • electron carrier activity • enzyme regulator activity • guanyl-nucleotide exchange factor activity • metallochaperone activity • mitochondrial RNA polymerase binding promoter specificity activity • molecular function regulator • molecular transducer activity • morphogen activity • negative regulation of molecular function • neurotransmitter receptor regulator activity • nucleic acid binding transcription factor activity • nutrient reservoir activity • positive regulation of molecular function • protein tag • receptor regulator activity • regulation of molecular function • signal transducer activity • structural molecule activity • transcription factor activity, core RNA polymerase binding • transcription factor activity, protein binding • transcription factor activity, transcription factor binding • translation regulator activity • transporter activity NUMBER OF TERMS: ~10k http://geneontology.org/
- 6. What is Molecular Function in GO? • Describes “function”…? GO:0003674 molecular_function Elemental activities, such as catalysis or binding, describing the actions of a gene product at the molecular level. A given gene product may exhibit one or more molecular functions.
- 7. Motivation • Is GO’s molecular function ontology really function, “little” processes or both? • Documented as a function • Sometimes looks like a process • Sometimes treated like a process • Confusion of thing with a function and the function • This can make modelling harder than it need be
- 8. A Couple of Observations • Pragmatically, we commit to GO – it’s the only show in town and it works • There’s a lot of chemicals around in GO MF • We are biochemistry….! • Probably few functions – strip out all the “non- function” stuff and see what’s left • Then we can look at the ontological nature of GO MF • Also, re-create in a more sustainable form
- 9. It’s all work in progress
- 10. A “tangled” ontology of amino acids 12
- 11. There are several dimensions of classification here • The amino acids themselves – a chemical dimension • The size of the amino acids side chain • The charge on the side chain • The polarity of the side chain • The hydrophobicity of the side chain • We can normalise these into separate hierarchies then put them back together again • Our goal is to put entities into separate trees all formed on the same basis • Size only talks about size; amino acid only talks about chemical composition (based on an alpha-carbon with an amino and carboxylic acid group);and so onof classification 13
- 13. The process • Hand-crafted ontologies with a polyhierarchy are “tangled” • Usually axiomatically lean • We classify along one axis and use “restrictions” to other modules to capture other axes • Then re-build the polyhierarchy using the axiomatically rich ontology 15
- 14. “Pulling out” dimensions • Each separate tree must be the same kind of thing • We don’t mix continuants, processes, qualities, etc • We don’t mix our classification by, for instance, structure and then charge • We do that compositionally via defined classes and automated reasoners 16
- 15. The amino acid pattern 17 Class: AminoAcid SubClassOf: hasSize some Size, hasPolarity some Polar, hasCharge some Charge, hasHydrophobicity some Hydrophobicity
- 16. An amino acid 18 Class: Lysine SubClassOf: AminoAcid, hasSize some Large, hasCharge some Positive, hasPolarity some Polar, hasHydrophobicity some Hydrophilic
- 17. Rebuilding the hierarchy • Class: LargeAminoAcid – EquivalentTo: AminoAcid • and hasSize some Large • Class: PositiveAminoAcid – EquivalentTo: AminoAcid – and hasCharge some Positive • Class: LargePositiveAminoAcid – EquivalentTo: LargeAminoAcid and PositiveAminoAcid 19
- 18. A “tangled” ontology of amino acids 20
- 19. Other Ontology Topics as Factors in GO MF molecular function chemical chemical role reaction biological process cellular component cell protein sequence 40-60% of terms mention chemicals
- 20. Some GO Terms GO MF glucose import cytosolic calcium ion transport hydrolase activity tyrosine binding retroviral strand transfer activity electron carrier activity
- 21. Binding • ~2k terms in the binding bit of GO MF • Remove the chemicals • Leaves “binding” • There is a function “to bind” • There is a process of binding” • Linguistically – an infinitive and a gerund/nominalised verb
- 22. More “to bind” Functions? • “to bind” is the basic function • Specialise to to bind covalently, to bind via hydrogen, to bind electrostatically but these are built compositionally with reference to other ontologies
- 23. Chemorepellant - chemoattractant activity GO:0042056 chemoattractant activity Providing the environmental signal that initiates the directed movement of a motile cell or organism towards a higher concentration of that signal. GO:0045499 chemorepellent activity Providing the environmental signal that initiates the directed movement of a motile cell or organism towards a lower concentration of that signal. To diffuse
- 25. Angels on the head of a pin
- 26. Distinctions with no (practical) difference • “Distinction without a difference” – making a distinction where none exists • Distinctions may exist, but does one need to make them? • Does a distinction make a practical difference to the use case in hand? • Make no distinction unless it makes a difference • Beware of consistency…
- 27. New function hierarchy • RealizableEntity – ToCatalyse – ToBind • ToMark – ToStore – ToDiffuse – ToTransport – ToMaintainIntegrity – ToProtect – ToModulate • ToRegulate – ToTransduce
- 28. Is realized in Standard pattern – some and only Has realizable entity Gene product Realisable entity Biological process
- 29. RO candidate: capable_of = shortcut Is capable of Gene product Biological process
- 30. Some patterns • hasRealisableEntity some (to_bind and realisedIn only (binding and hasInput some chemical))) • Add “playsrole some role” for a chemical role like drug • hasRealisableEntity some (to_catalyse and realisedIn only (catalysis and hasInput some chemical and hasOutput some chemical))
- 31. Actually doing it • Programmatically using Tawny-OWL • Asserted tree of molecular realisables and molecular processes • Defined classes for the actual terms • May have to restrict to OWL EL for practical reasons • We shall see…
- 32. Strategies for Defined Classes • Total post co-ordination • Total pre co-ordination • Pre co-ordinate those classes that have been used in annotation
- 33. How many GO MF terms are used? Annotation file Homo sapiens: Canonical accessions from UniProt (goa_human.gaf.gz) Unfiltered GOA UniProt gene association file (goa_uniprot_all.gaf.gz) Total number of GO- UniProt annotations 354 515 ~ 354K 294 208 149 ~ 294M Unique UniProt IDs 19 055 ~ 19K 45 968 890 ~ 46M Unique active Molecular Function classes 3 947 ~ 4K 7 521 ~ 7K Unique active Molecular Function classes used more than 5 times 1 313 ~ 1K
- 34. What have we found? • Very few functions • … and some look dispositional • It looks like physics • Most functions involve binding – makes sense • We separate realisables and processes • We live with a bit of “replication” • With molecular processes, do we need molecular funtion? • WE change the upper reaches of GO MF, but… • Does it make any practical difference?
- 35. Formality • Ontological formality • Making the right distinctions drives consistent use of relationships • Facilitates the kind of analysis we’ve done • Can also be a barrier to progress • Representational formality • Knowing what is being said is useful • Allows clean interpretation • Enables useful reasoning
- 36. Pragmatic Decisions • Commit enough to achieve goals • If re-using take on the commitments of that ontology – If using OBO commit to OBO – If what you’re using uses something with which you disagree – get over it • Axiom pragmatics • Don’t represent that which isn’t needed • Truth and beauty • A counsel of perfection is a counsel of despair • I’d make “gene product” explicit
Editor's Notes
- #4: Informal definitions of the words formality and pragmatics I build ontology based applicationis and pragmatics come into play I like formality (up to a point) but I’d prefer an applicationi that does something over a formal ontology that is not usable – both is great, but I scarifice formality first
- #5: 1) #Slide with molecular function title #add textbox with number of terms #URL: http://geneontology.org/ D-alanyl carrier activity acetylcholine receptor regulator activity antioxidant activity binding calcium channel regulator activity catalytic activity channel regulator activity chemoattractant activity chemorepellent activity core DNA-dependent RNA polymerase binding promoter specificity activity electron carrier activity enzyme regulator activity guanyl-nucleotide exchange factor activity metallochaperone activity mitochondrial RNA polymerase binding promoter specificity activity molecular function regulator molecular function regulator molecular transducer activity morphogen activity negative regulation of molecular function neurotransmitter receptor regulator activity nucleic acid binding transcription factor activity nutrient reservoir activity positive regulation of molecular function protein tag receptor regulator activity regulation of molecular function signal transducer activity structural molecule activity transcription factor activity, core RNA polymerase I binding transcription factor activity, core RNA polymerase II binding transcription factor activity, core RNA polymerase III binding transcription factor activity, core RNA polymerase binding transcription factor activity, protein binding transcription factor activity, transcription factor binding translation regulator activity transporter activity
- #7: title: GO Molecular function 1. molecular_function (GO:0003674) "Elemental activities, such as catalysis or binding, describing the actions of a gene product at the molecular level. A given gene product may exhibit one or more molecular functions." - 1. above in a box at the top of the slide with a text box below into which I can put bullets. the first bullet is * Describes "function"....?
- #11: first slide is a tangled hiearchy (title "Normalisation 1" "Vehicle" at the top the leaves are: fast red sports car fast green sports car red lorry slow yellow lorry green van fast red motor cycle black estate car green saloon car red estate car Then some intermedate, "defined classes" such as: red vehicle green vehicle fast red car red car and any you can think of andmake it tangled
- #12: second slide (title "Normalisation 2") separate out a set of hierarchies Vehicle colour speed style and if you can fit it on, an axiom pattern of Class: Vehicle SubClassOf: hasColour some Colour hasStyle some Style hasSpeed some Speed
- #13: Normalisation; a paper from Alan Rector (2003)
- #22: This pulling out of non-function aspects of GO MF I not complete Most aspects have OBO support Not electron and energy
- #26: title: Chemorepellant - chemoattractant activity below, 1 and 2 are some kind of box with the GO term and Id as some form of title with the definition below. this links down to a blob containing 3. 1. chemoattractant activity (GO:0042056) Providing the environmental signal that initiates the directed movement of a motile cell or organism towards a higher concentration of that signal. 2.chemorepellent activity (GO:0045499) Providing the environmental signal that initiates the directed movement of a motile cell or organism towards a lower concentration of that signal. 3. both linking down to a blob containing "To diffuse"
- #27: RealizableEntity Some of these functions l look dispoitional To store, to diffuse and to structurally maintain Lots of these “functyions” als also imply bidning This is not a surprise as some binding must happen for anything to happen(as-subclasses ToCatalyse :comment "To reduce the activation energy of a reaction, enabling it to go faster.") (defclass ToBind :comment "To interact tightly with another entity, longer than transiently, such that separating the entity requires significant energy. ToBind functions are often transitive; A has a function ToBind B, then vice versa is also true.") (defclass ToMark :comment "To bind between this entity X, and another entity Y, so that a third entity Z can also be bound, and thereby interact with Y." :super ToBind)) ;; #+end_src (defclass ToStore :comment "To contain a substance for later use.") (defclass ToDiffuse :comment "To spread outward from a single point as a result of Brownian motion.") (defclass ToTransport :comment "To enable the movement of an entity in a directed manner.") (defclass ToMaintainIntegrity :comment "To keep the same structure, shape or organisation despite physical forces, either in compression or in extension.") (defclass ToProtect :comment "To prevent an event occuring to this or another entity.") (defclass ToModulate :comment "To alter the strength or quantity of some other realisable entity.") (defclass ToRegulate :comment "To modulate in a directed manner, as part of a feedback loop." :super ToModulate) (defclass ToTransduce :comment "To change energy from one form to another.")
- #37: Talk about Mungall et al’s normalisation of GO Partial; not down to the bare functions Intersting point around ribose sugars