OBO-Edit tutorial

David Osumi-SutherlandFlyBase / Virtual Fly Brain / OBO-Edit

Working Group (OEWG)

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

• The latest version of OE2 (beta release), is here:– http://oboedit.org/2.1betarelease/

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.

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)

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

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

Quantifiers• It is critical to be aware of the direction of quantifiers when using OBO

relations:

True: All breasts are part of some humanFalse: All humans have breasts

True: All vertebrate motor neurons release neurotransmitter acetylcholineFalse: 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 neckFalse: All lion’s neck connected_to some lion’s mane

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.

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

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.

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.

Demo – OBO basics

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)

Browsing

Browsing - TreesThe 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

Click to expand or contract branch

Preferences

help

save a picture

Quick Filtering

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

Preferences

help

save a picture

Preferences

help

save a picture

Graph viewer setup

For an uncluttered view:

Browsing - graphsA good way to view and browse ancestral relationships, graphs of ancestors via transitive relations answer questionse.g.- what is X? What is X part of? What does X develop from?

Note – currently requires link pile reasoner to be turned on.

Browsing – The Text Editor

Basic Searching - single leg

Basic searching – multi-leg

Add new leg

AND/OR

Remove legnesting (parentheses)

All searches can also be filters or renders

Rendering options

Editing

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.

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

Drag and drop term move

Drag and drop term move

Drag and drop term move

Drag and drop term merge

Making new terms

• First, make sure your ID generator is set up correctly:

Edit profile

ID prefix ID length start from end at

Create new child

Committing

Check this box to commit text edits automatically.

Note, committing will not change your ontology file

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!)

Parent EditorDelete parent relationship

Does what it says. But be careful it adds is_a parents by default. For other relations, switch after adding

Graph Editor

Graph Editor

Hide parent terms show parent terms

Hide child terms show child termshide term

• Right click provides editing options and hide-all

• Choosing quick filtering => manageable view

Making new relationships in the graph editor – demo only

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.

Managing multiple inheritance

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

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!)

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.

Multiple inheritance needed• Name: ORN ab1a • Def: A cholinergic olfactory neuron whose

dendrite innervates an ab1 basiconic sensillum on the 3rd 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

It is difficult to keep track of multipleclassification chains to: ensure completeness;avoid redundancy;avoid introducing error due to inheritanceof classification criteria from a distant ancestor

Multiple inheritance is very hard to manage by hand

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

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

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

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

Cross Product Demo

• Using terms from other ontologies– cholinergic neuron– olfactory sensillum

Making new cross product terms

• Add a new root class:

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

Useful renders for working with cross-products

• Cross-Product detector:

• Multiple asserted inheritance detector:

• Unclassified term detector:

• Incompletely classified term detector:

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.

Hidden assertion demo

Detecting redundancy with the reasoner

Redundant relationship

Use the Rule Base Reasoner*

*Link pile reasoner over-flags redundancy when cross-product terms are present

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

Advanced Searching

• OE2 can combine string searching and logical querying.

• Logical querying requires the reasoner to be turned on.

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:

Logical queries

How is sensillum classified?

What does adPN DL1 develop_from ?

Note – this query has no OWL equivalent

** Note – reasoner required **

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.

Creating and maintaining a helper term filter

Load / Save

First leg finds helper term

2nd leg finds terms that classify helper term

1. Open foreign ontology and run the rule based reasoner2. In the search tool, add the following two filter legs for each helper term

3. Save filter for future maintenance / use as a save filter

Saving helper terms

Saving helper terms

Check filter terms

Make sure “allow dangling parents” is NOT checked

Record version of foreign ontology here Avoid importing foreign ID rules

Saving helper terms

Load helper term filter

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.

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:

• Current developers– Amina Abdulla– Chris Mungall– Jennifer Deegan

• Former developers– John Day-Richter– Nomi Harris

Acknowledgements – OBO-Edit developers

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

Acknowledgments

• Michael Ashburner• FlyBase• Virtual Fly Brain• ICBO