Representing Part Relationships Between Developing Structures

1. Representing Part Relationships Between Developing Structures

2. Anatomy Ontologies – a MOD prespective.

3. What literature curators need 1.The ability to query the ontology to home in on candidate terms based on limited available information. Useful queries for this: • give me a list of all the types of X that are part of Y. • find where structures referred to by candidate terms are located. 2. A way to curate even when the available anatomical data is vague.

4. What database users need • The ability to precisely extract biologically relevant information from an ontology – rather than navigating some convoluted DAG • E.g.- for any term X • Locate X, • what is X, • what subtypes does X have • What parts does X have • Curations grouped accurately according to type and part relationships.

5. Argument for making all part relationships into integral_part

6. Cardinality Anatomy Ontology terms can be classed according to the number of structures per whole organism (C). 1. Many per org (C>1) – bristle, scale or neuron - always possibility of further subdivision – e.g.- neuron % motor neuron % ventral tp motor neuron 2. Fixed/known number per org: e.g.- limbs or (perhaps) segments (C>1) 3. One per organism (C=1) – adult head 4. Less than one per organism - sexually dimorphic structures (C=0.5)

7. The 2 flavours of part relationships*: • X part_of Y: All instances of X are part of some instance of Y. (symbol: <) • Obligatory (?) • Y has_part X: All instances of Y have some instance(s) of X as a part. (symbol: >) • When both of these conditions are satisfied, the relationship is known as integral_part. (symbol: <>) * For the sake of simplicity, these definitions avoid time/stage. These will be dealt with later.

8. Example: sex comb only on male prothoracic leg; all legs have claws If we were only using part_of (<) then this is legal: leg % male prothoracic leg < sex comb < claw With integral_part (<>), we are restricted to this: leg % male prothoracic leg <> sex comb <> claw (% = is_a) Deductions: All legs have a claw as a part. Prothoracic leg is_a leg.  Prothoracic legs have a claw Sex comb part_of leg

9. How literature curation works Curation of expression or phenotype with any term X can mean: expressed/having phenotype in all types of X OR expressed/having phenotype in some unspecified subset of X (X is the most precise term we can curate to, given the evidence presented in the paper being curated)

10. Grouping – the need for has_part FOR: • Gene 1 - expressed in X (subset) • Gene 2 - expressed in Y • If the only known part relationship between X and Y is: • Y part_of X • It is not safe to group these two curations - we don't know whether the curation to X was made because of expression in a type of X that has a Y as a part. • X has_part Y • Then these two curations can be safely grouped - all types of X have a Y as a part.

11. Representing sexual dimorphism • organism • <> gonad • % testis • % ovary • % male organism • <> testis • % female organism • <> ovary • <> head • <>brain

12. Part relationships during development

13. Types of Developing Structure anlage Contiguous tissue defined by lineage labelling as contributing all or the majority of its cells to some specified mature structure but not (yet) having distinct morphological boundaries. primordium Contiguous tissue defined by lineage labelling as contributing all of its cells to one or a few specified mature structures and having morphologically distinct boundaries germ layer Primary division of embryo established just prior to &/or during gastrulation. Initially constituting a contiguous tissue contributing all of its cells a large but limited set of mature structures. compartment Contiguous tissue defined by lineage labelling as consisting of cells unable to cross a *compartment boundary* to mix with cells in a neighbouring tissue with which it is contiguous during development.

14. Types of Developing Structure These terms group multiple primordia and anlage over the complete development of the system, part or organ. Developing system (e.g.- developing nervous system) Developing (cardinal) body part – e.g.- developing head Developing organ (e.g.- developing brain)

15. Relationships linking stage to anatomy • Ts= stage n: starts during or after stage n • Te= stage n: ends during or before stage n e.g.central brain primordium; ts=6 te=8 Note: These definitions allow for cases where the transition between sub-types of a term occur spread out over multiple stages.

16. Identity and development • We need some concept of identity for continuants (biological structures existing over time) that can account for changes composition over time (X can have diff parts at diff stages). • Ideally, shifts in identity during development, e.g.- neuroblast -> neuron, will be based on intrinsic criteria. This could be morphological (e.g.- having an axon), or perhaps (?) functional (heart starts pumping).

17. Intrinsic identity and part_of developing nervous system ; ts=4 te=16 < neuron X ; ts=13 te=16 ~ neuron X’ ts=16 … < neuron Y ts=14 te=16 ~ larval nervous system ts=16 … < neuron X’ ts=16 … • Reasoning: • Part_of : all neuron X are part_of (some) developing nervous system •  - all neuron X after the stage that developing nervous system is considered mature have to get a new name - identity is being ascribed extrinsically.

18. Defining has_part for developing structures This definition cannot be used for part relationships between a developing stucture and parts it instantiates at different stages: For Y has_part X: All instances of Y at all times (stages), have some instance(s) of X as a part

19. Part relationships during development developing central nervous system; ts=3 te=16 <> developing brain; ts=3 te=16 <> central brain anlage; ts=5 te=5 ~ central brain primordium; ts=6 te=8 <> central brain primordium; ts=6 te=8 Is there some definition of has_part that is still useful for grouping curations and for reasoning, but that can be used here?

20. Possible alternative def for has_part • For Y has_part X: All instances of X have some instance of Y as a part during the stages that Y exists. e.g. - <> developing brain; ts=3 te=16 <> central brain anlage; ts=5 te=5 ~ central brain primordium; ts=6 te=8 <> central brain primordium; ts=6 te=8 Tells us that developing brain has central brain anlage as a part during stage 5 and central brain primordium as a part during stages 6-8 • ie- given the stage, we can list reliably list parts

21. Poss solution to all – seemed like a good idea in the pub last night. Term X ts=4 te=8 <> Term Y ts=6 te =10 Y part_of X during the stages that both X and Y exist: In this case stages 6-8 X has_part Y during the stages that both X and Y exist: In this case stages 6-8

22. develops_from As long as part of the definition of ‘B develops_from A’ includes: A and B abut in time: there is no instance that is both A and B simultaneously. Then we can use overlap between stages to specify a range during which a transition occurs. Or, if A(Te) and B(Ts) are adjacent stages – we can tie the transition to a stage boundary.

23. Tying develops_from transition to stage term X te=n ~ term Y ts=n+1 (note ts>n+1 would not be legal) Implies that the transition from X to Y occurs at the stage transition. term X te=n ~ term Y ts <=n Implies that the transition from X to Y occurs at some point during the overlap in stages between X and Y.

25. Using cardinality in part reasoning developing central nervous system C=1 ts=3 te=16 < developing brain C=1 ts=3 te=16 < central brain anlage ts=5 te=5 C=1 ~ central brain primordium ts=6 te=8 C=1 < central brain primordium ts=6 te=8 C=1 All central brain anlage are part_of some developing brain. But in any one organism there is only 1 central brain anlage and one developing brain. So developing brain must have central brain anlage as a part during the stages that central brain anlage exists.