1. OBO-Edit tutorial David Osumi-Sutherland FlyBase / Virtual Fly Brain / OBO-Edit Working Group (OEWG)

2. Resources Slides and test tutorial can be downloaded from the bottom of the Tutorial wiki page: – http://www.bioontology.org/wiki/index.php/OBO- Edit http://www.bioontology.org/wiki/index.php/OBO- Edit The latest version of OE2 (beta release), is here: – http://oboedit.org/2.1betarelease/

3. Your backgrounds Who here has never used an ontology editing tool? Who here is an OBO-Edit user? – If you are, have you used Cross-Products? Who here is a Protégé user? Protégé 3 Protégé 4 – With reasoner? For those of you who speak OWL(ish), I'll try to provide translations to OWL Manchester syntax.

4. OBO 101 An ontology contains terms (e.g. hand) and relationships (e.g. hand has_part finger) Terms refer to types (classes). Types are classifications of things (instances) in the real world, based on some set of criteria. – My left hand is an instance of the type hand The criteria for membership of a class (type) is recorded using textual definitions, relationships, or some combinations of the two – name: hand – def: “An anatomical structure that has four fingers and a thumb and is attached to the end of an arm.” [reference: DOS] – relationship: hand has_part finger – relationship: hand has_part thumb – relationship: part_of arm Image from Gray’s Anatomy (copyright expired)

5. OBO basics- instance/type distinction If OBO terms refer to types, why worry about instances? – instances are central to defining OBO type-level relations OBO OWL: – OWL class = OBO type – OWL individual = OBO instance

6. OBO relations Instance level relations (by convention written in bold) – 'my left little finger' part_of 'my left hand' Note – quantifiers – all, some – are not needed. Type level relations (by convention, written in italic). – Type level relations are defined using instance level relations + quantifiers. In OBO, the quantifiers (all, some) are buried in the definition of the type-level relation. – e.g.- X part_of Y is defined as: » for all x,t if Xxt then there is some xy such that Yyt and x part_of y at t OBO OWL: – OBO instance level relation = OWL property – In OWL, quantifiers are used explicitly in ontology construction when relating classes OBO: finger part_of hand can be written in OWL using the OBO instance level relation with added quantifiers: all finger part_of some hand * – OBO is_a = OWL SubClassOf *Ignoring the time component of the OBO definitions, as this cannot be expressed in OWL

7. Quantifiers It is critical to be aware of the direction of quantifiers when using OBO relations: True: All breasts are part of some human False: All humans have breasts True: All vertebrate motor neurons release neurotransmitter acetylcholine False: All neurons that release acetylcholine are vertebrate motor neurons. Be especially careful in cases where the instance level relation is symmetric: True: All lion’s mane connected_to some lion’s neck False: All lion’s neck connected_to some lion’s mane

8. Relationships and definitions You should think of the relationships a term has as a formalised part of their definition. A regular relationship in OBO (SubClassOf in OWL) specifies necessary conditions for membership of a class. – e.g. finger part_of hand (all finger part_of some hand) states that a necessary condition of being in the class finger is to be part of some hand.

9. Transitivity If a relation is transitive: – A rel B rel C rel D therefore A rel D U1 neuron is_a U neuron is_a motor neuron – therefore U1 neuron is_a motor neuron ellipsoid body part_of central complex part_of adult brain – therefore ellipsoid body part_of adult brain

10. Transitivity and redundancy ellipsoid body part_of central complex part_of adult brain – therefore ellipsoid body part_of adult brain therefore asserting the relationship "ellipsoid body part_of adult brain" in your ontology would be redundant.

11. Some simple reasoning U neuron part_of larval antennal segment – (All U neuron part_of some larval antennal segment) U1 neuron is_a U neuron therefore U1 neuron part_of larval antennal segment – (All U neuron part_of some larval antennal segment; U1 neuron SubClassOf U neuron therefore…) So, adding 'U1 neuron' part_of 'larval antennal segment’ would be redundant.

12. Demo – OBO basics

13. Basic OBO-Edit2 editing setup - 2 x Ontology Tree Editor (OTE) - One parent editor - One text editor - One search panel - One reasoner manager - One graph viewer (Note - currently only works with Link Pile Reasoner on)

16. Browsing

17. Browsing - Trees The ontology tree editor is a good way to browse down the ontology graph, but not all parents visible in one view Click to expand or contract branch

18. Preferences help save a picture Quick Filtering

20. Browsing - parents The parent editor provides a quick way to check all parental relationships – usually these are not all these are visible in a single tree view

21. Preferences help save a picture

22. Preferences help save a picture

23. Graph viewer setup For an uncluttered view:

24. Browsing - graphs A good way to view and browse ancestral relationships, graphs of ancestors via transitive relations answer questions e.g.- what is X? What is X part of? What does X develop from? Note – currently requires link pile reasoner to be turned on.

25. Browsing – The Text Editor

26. Basic Searching - single leg

27. Basic searching – multi-leg Add new leg AND/OR Remove legnesting (parentheses)

28. All searches can also be filters or renders

29. Rendering options

30. Editing

31. Drag and drop editing in the ontology tree editor (OTE) Left clicking a term choose it Right clicking displays a menu of editing options Dragging and dropping single or multiple terms allows terms to be copied, moved or merged.

32. Global vs local selection modes local mode -selection in other components doesn’t affect selection here local mode -selection in other components doesn’t affect selection here global mode - 2 way auto sync with other components global mode - 2 way auto sync with other components

33. Drag and drop term move

36. Drag and drop term merge

38. Making new terms First, make sure your ID generator is set up correctly: Edit profile ID prefix ID length start from end at

39. Create new child

40. Committing Check this box to commit text edits automatically. Note, committing will not change your ontology file

41. Deletion, obsoletion, destruction … deletes the relationship between the selected term and its immediate parent in the ontology tree editor. When the selected term has only one parent, this option switches to: OTE – right click menu: … changes the status of term to obsolete. The OBO file retains the ID for future reference and to prevent re-use. To indicate replacement terms, drag suitable terms to the obsoleted term => Within the context of a single editing session, or a pre-release file, you may wish instead to destroy the term completely (BUT BE CAREFUL!)

42. Parent Editor Delete parent relationship Does what it says. But be careful it adds is_a parents by default. For other relations, switch after adding

43. Graph Editor

44. Hide parent terms show parent terms Hide child terms show child terms hide term Right click provides editing options and hide-all Choosing quick filtering => manageable view

46. Making new relationships in the graph editor – demo only

47. Time savers Cloning – Right click clone option makes clone of chosen term – identical in every way except for ID and ‘CLONE OF’ appended to term name Create multiple children – Right click ‘create multiple children’ option. Does what is says on the box. Pops up interface were a bunch of new terms can be named at once.

48. Managing multiple inheritance

49. Disjunction X disjoint_from Y – Nothing that is an instance of X is also an instance of Y. e.g. anatomical structure disjoint_from biological process – Nothing exists that is an instance of both of these types. – Extremely useful for error checking – also speeds up some reasoners OBO OWL – 0BO disjoint_from ≅ OWL DisjointWith

50. Using the reasoner to check for disjoint violations - demo In the test ontology, make one of the children of biological process an is_a child of sensillum. Now run the link pile reasoner Undo Making disjoints - demo – by hand – automatically making all children disjoint (use sparingly!)

51. Ways to classify neurons sensory – Sensory modality – Sense organ motor interneuron – local – relay neurotransmitter – serotonergic, – dopaminergic… Location – cell body – fasciculation pattern (e.g.- labial nerve) – innervation pattern (antennal lobe glomerulus DL1) all siblings in the same color are (probably) disjoint_from each other.

52. Multiple inheritance needed Name: ORN ab1a Def: A cholinergic olfactory neuron whose dendrite innervates an ab1 basiconic sensillum on the 3 rd segment of the antenna. Like other antennal olfactory neurons, it sends an axon through the antennal nerve that innervates a single antennal lobe glomerulus DL1 – olfactory neuron – cholinergic neuron – antennal sensory neuron – DL1 innervating neuron

53. It is difficult to keep track of multiple classification chains to: ensure completeness; avoid redundancy; avoid introducing error due to inheritance of classification criteria from a distant ancestor Multiple inheritance is very hard to manage by hand

54. Cross Products In OBO, cross products, also known as intersections, provide a way to record necessary and sufficient definitions. necessary and sufficient definitions allow classification to be automated using reasoners OBO OWL – intersection_of ≅ EquivalentTO

55. Genus and Differentia Anatomy of a cross product: – name: antennal sensillum – genus: sensillum – differentium: (part_of antenna) In OBO format – intersection_of: sensillum – intersection_of: part_of antenna In OWL: – EquivalentTO: sensillum and part_of some antenna

56. OBO-Edit reasoners OBO-Edit2 currently has 3 reasoners In the near future, 2 of these will be retired, leaving just the ‘rule based reasoner’ (RBR) Currently the link pile reasoner is needed for flagging disjointness violations and for running the graph viewer. For everything else you should use the RBR

57. Cross Product Demo Choose the term 'antennal sensillum' – Check out the text editor cross product tab Turn the reasoner off. – You should see antennal sensillum at the root Run the rule-based-reasoner – check out how the term is integrated non- redundantly into the classification hierarchy. – view the parent editor

58. Cross Product Demo Using terms from other ontologies – cholinergic neuron – olfactory sensillum

59. Making new cross product terms Add a new root class:

60. Cross Product demo Making new cross products – glutamatergic neuron – taste sensillum – chemosensory sensillum Re-run the rule-based-reasoner Check the sensillum hierarchy – Explain how olfactory sensillum got its parent

61. Useful renders for working with cross- products Cross-Product detector: Multiple asserted inheritance detector: Unclassified term detector: Incompletely classified term detector:

62. Combining Cross-Products with relationships => hidden assertions How can we record the generalization – All neurons with the function ‘smell’ are cholinergic? – name: olfactory receptor neuron – intersection_of: neuron – intersection_of: has_function smell – relationship: releases_neurotransmitter acetylcholine – (OWL: EquivalentTo( neuron AND has_function some smell ), SubClassOf( releases_neurotransmitter some acetylcholine ) Why is this potentially dangerous? – Future editors using ‘has_function smell’ to record the function of a neuron class may not be aware that they are adding the assertion that the class is cholinergic Safeguards: – if neurons classifed by neurotransmitter are disjoint, the reasoner can flag contradictions. – Keep a record of all examples (perhaps as a standardised comment) – State this assertion in the term definition with a link to a supporting reference.

63. Hidden assertion demo

64. Detecting redundancy with the reasoner Redundant relationship Use the Rule Base Reasoner* *Link pile reasoner over-flags redundancy when cross-product terms are present

65. If the reasoner is flagging relationships you don’t think are redundant Are you sure your intended meaning for a relationship is transitive? – e.g.- develops_from (transitive) is sometimes used as if it means ‘directly develops from’ (non- transitive) – In that case – request a new relation. – If you are interested in how to link relations such as develops_from and develops_directly_from so that they can be used for reasoning, please ask me or Chris after the tutorial

66. Advanced Searching OE2 can combine string searching and logical querying. Logical querying requires the reasoner to be turned on.

67. Logical queries OWL-DL: sensillum and part_of some head The first leg of the search finds all subtypes of sensillum. The second leg finds all parts of the head. The ‘matches all’ radio button ensures the two legs are combined by a boolean AND. ** Note – reasoner required ** Find all sensilla that are part of some head:

68. Logical queries How is sensillum classified? What does adPN DL1 develop_from ? Note – this query has no OWL equivalent ** Note – reasoner required **

69. Importing foreign ‘helper’ terms Formalising definitions is likely to require terms from other ontologies. If you want to reason using the classification from another ontology, you need to import the full classification of each term. In order to keep up-to-date, you need a mechanism to re-import the foreign terms you use.

70. Creating and maintaining a helper term filter Load / Save First leg finds helper term 2 nd leg finds terms that classify helper term 1.Open foreign ontology and run the rule based reasoner 2.In the search tool, add the following two filter legs for each helper term 3. Save filter for future maintenance / use as a save filter3. Save filter for future maintenance / use as a save filter

71. Saving helper terms

72. Check filter terms Make sure “allow dangling parents” is NOT checked Record version of foreign ontology here Avoid importing foreign ID rules

73. Saving helper terms Load helper term filter

74. Refreshing helper terms The examples I’ve shown here use term names. This make the filter easy to read and edit, but names often change. Therefore more sustainable to use IDs instead.

75. Instantiating inferred is_a for release If your users are not using your ontology with a reasoner, you made need to pre-reason for them. To do this, you can use the ‘save implied links’ function in the save interface:

76. Current developers – Amina Abdulla – Chris Mungall – Jennifer Deegan Former developers – John Day-Richter – Nomi Harris Acknowledgements – OBO-Edit developers

77. Acknowledgements - OEWG Amina Abdulla, Chris Mungall, Karen Eilbeck, Suzanna Lewis, - BBOP, LBNL, Berkeley, CA, USA Midori A. Harris, Jennifer Deegan, Amelia Ireland, Jane Lomax - GO-EBI, Hinxton, UK David Hill, Alexander D. Diehl, Harold Drabkin - MGI, The Jackson Laboratory, Bar Harbor, ME, USA Karen R. Christie - SGD, Department of Genetics, Stanford University, Stanford, CA, USA Tanya Berardini - TAIR, Carnegie Institution, Department of Plant Biology, Stanford, CA, USA Petra Fey - DictyBase, Northwestern University, Chicago, IL, USA Carol A. Bastiani, Ranjana Kishore - WormBase, California Institute of Technology, Pasadena, CA, USA Victoria Petri - RGD, Medical College of Wisconsin, Milwaukee, WI, USA Colin Batchelor- Royal Society of Chemistry, Cambridge UK Shuly Avraham - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY Pankaj Jaiswal - Gramene, Department of Plant Breeding, Cornell University, Ithaca, NY, USA Melissa Haendel - ZFIN, University of Oregon, Eugene, OR, USA John Osborne - Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL, USA

78. Acknowledgments Michael Ashburner FlyBase Virtual Fly Brain ICBO