1. Homology

2. Homology Review Which of the following structures are homologous?
Definition: Structures (including genes) are homologous if they evolved from some structure in a common ancestor
Human arm
Lobed-fin fish fin
Bat wing
Bird wing
Insect wing
Homologous
forelimbs
not homologous as wings
not homologous as forelimbs or wings
Wings are functionally classified, and are analagous structures

3. Why do we care about homology when building an anatomy ontology?
Consider an anatomy ontology of vertebrates:
skeletal system
cranial skeletal system
parietal bone (in_organism human)
parietal bone (in_organism zebrafish)
frontal bone (in_organism human)
frontal bone (in_organism zebrafish) f pa
Homologous : frontal bone (zebrafish) and parietal bone (human)
Different genes and developmental processes may underlie the development of the zebrafish frontal and the human frontal, even though they have the same name and are similarly located

4. Homologous_to A1 in B1 homologous_to A2 in B2 iff exists A3, B3:
A1 in B1 descends_from A3 in B3
&
A2 in B2 descends_from A3 in B3
(Note B1 and B2 must both be subclades of the clade descending* from D)
(*In the genealogical sense)
Note: Do we need to include time (exists & existed)? FN – just to be on the safe side we can include time – it's not useful but it could stop the some people complaining and it won't affect the logic at all.
[edit] relation to what is in RO proposed

5. Directly_descends_from
x1 directly_descends_from x2 iff there are y1, y2 such that:
- y1 is an organism
- x1 is an anatomical structure
- x1 part_of y1
- y2 is an organism
- x2 is an anatomical structure
- x2 part_of y2
- y2 is a parent of y1
the genetic sequence that determined the morphology of x1 is partially a copy of the genetic sequence that determined the morphology of x2.
descends_from is the instance level relation which is the transitive closure over directly_descends_from

6. Descends_from A in B descends_from C in D :
For all A(a) -> exists b, d, c: B(b) & C(c) & D(d)
a part_of b
a descends_from c
c part_of d
(Note – B must be a subclade of the clade descending* from D)

7. Note that there are a number of synonyms for descended_from, including
'evolutionarily_derived_from' which is currently in ROproposed as follows:
id: OBO_REL:evolutionarily_derived_from
name: evolutionarily_derived_from
def: "Instance 3-ary relation: x edf y as T iff x specified_by gx and
gx ancestral_copy_of gy and gy specifies y" []
synonym: "derived_from" RELATED []
synonym: "descended_from" RELATED []
synonym: "evolved_from" RELATED []
is_transitive: true

8. What are Characters? a,b - symphysial bone margins straight
c - anterior symphysial bone margin concave, resulting in oval gap between bone halves

9. Character “optimization”
Method to infer ancestral conditions (features)
Inferred ancestral condition dependent on phylogenetic tree
I.e. different trees may imply differently reconstructed ancestors

10. Ancestral uncertainty
Species A B C D E
Feature + - + + -
+/-
+/- +
Tree #1
+/-

11. Ancestral certainty Species A C B D E Feature + + + - - +/- - Tree #2

12. I. Bilaterians Heart presence/absence optimized on Bilaterian tree + +
+/- + _
+/-
No heart
in ancestor
of Bilateria
+/- + _ No
+/- + _ _ _ _ _ _ _ _ _ _ _ _ _ + _ _ _
+/- _ _ _ + _ _ _ _ _ _ _ _ _ _ _ _ _
Phylogeny from Garey, 1999

13. Character Optimization
Tree - including an ‘out group’
Character Matrix - states for taxa at tips of tree
Assign values from column of matrix to tree
‘Polarize’ the state at the root using the outgroup

25. Homology Evidence Codes
Inferred from morphological similarity
Inferred from positional similarity
Inferred from developmental similarity
Inferred from compositional similarity
Inferred from gene expression similarity
Inferred from phylogeny

27. Use case: Query for phenotypes affecting the human frontal bone and its homologous structure in other species.
Homologs = Synonyms
How and where should homology information be captured?
Homology between genes is already determined and recorded by the model organism community

28. Gene homology
Types of gene homology:
Genes that diverged due to a speciation event are termed orthologs
Genes that diverged due to a duplication within a species are termed paralogs
Gene orthology is recorded using different types of evidence:
FuguA
Conserved location:
mouse
HOXB
Kim et al., 1999

29. Homology between anatomical structures is already determined and but not yet captured in a database the evolutionary community
Homology assignments are based on specific kinds of evidence
IP: Inferred from Position
ID: Inferred from Development
IC: Inferred from Composition
Each homology assignment is associated with reference to a physical piece of evidence, a person, or literature.
Homology statements include evidence and citations, and different homology statements are used to create and refine phylogenies.

30. Homologous structures are already implicit within MODs ontologies

31. Discussion points
Do we need a relationship in OBO-REL to define homology? This is a symmetric relation between sisters and it is the relationship that requires evidence and attribution.
Should homology assignments be a top-down or bottom up approach?eg. Pairs of taxa vs. CARO-centric assignments? RE:domain experts are required. It might be easier to enlist help in a pairwise manner.
Homology needs to be captured for similarity searches. Text or synonym searches are insufficient. Does CARO take into account homology or is it a separate data set?
If two structures are deemed homologous, how does this information transfer down is_a chains? Need use cases.

33. Entity (AO): Ceratobranchial 5 teeth
Attribute (PATO): Is_present
Entity (AO): Ceratobranchial 5 teeth
Attribute (PATO): Is_absent