1. The Common Anatomy Reference Ontology (CARO) and queries across species
Melissa Haendel
ZFIN

2. Outline Current anatomy ontologies (AOs) Standardization CARO Homology
Querying across species

3. Why we build anatomy ontologies
Model organism databases (MODs): gene expression and phenotypes
bmp2b expression
ctcf -/- phenotype
Entities: otic vesicle, cardinal vein, retina
Entity (AO): tail
Quality (PATO): curved
Evolutionary biologists: recording character states
Danio rerio
Gyrinocheilus
Entity (AO): ceratobranchial 5 tooth
Quality (PATO): is_present
Entity (AO): ceratobranchial 5 tooth
Quality (PATO): is_absent

4. Advantages of using anatomy ontologies for expression, phenotype and character recording
Terms with written definitions:
More consistent annotation despite variable terminology
Stomach?
Logically defined relations between types:
Allows annotations to be grouped
finger part_of hand

5. CARO aims to standardize anatomy ontologies
Provide a template containing standard types and relations
Allow reasoning between different levels of anatomical granularity
Support the alignment of data and development of common tools
Allow reasoning across species

6. What is CARO?
CARO is a single-inheritance structural classification based on granularity
From the bottom up:
Cell component
Cell
Portion of tissue
Multi-tissue structure
From the top down:
Organism subdivision
Anatomical system
Acellular structures

7. Aligning a species-specific AO with CARO
zebrafish AO
CARO
is_a
Species-specific subtypes of CARO types

8. CARO and developing structures
zebrafish AO
CARO
Embryonic structures are not structurally classified

9. CARO integration with other ontologies
Gene Ontology
CARO
Xref
Cell and cell component are cross-referenced to GO and CL

10. CARO is structural
zebrafish AO
CARO
Cross species comparison requires formalization of homology

11. Outline Current anatomy ontologies (AOs) Standardization CARO Homology
Querying across species

12. Homology is hard f pa
zebrafish frontal bone homologous_to human parietal bone
Homology between anatomical entities requires evidence, attribution, and a formalized relation

13. Descent between individual organisms
O1 is an organism with structure A1
O1 is a parent of O2
The genetic sequence that participates in the development of the morphology of A2 is partially a copy of the genetic sequence that determined the morphology of A1. A3 O3 A2 O2
A2 directly_descends_from A1
A4 descends_from A1
directly_descends_from
descends_from between organisms can be used to define a type-level descends_from relationship between classes of organisms A1 O1

14. Descent between classes of organisms
descends_from T8 A8 T6 A2 T2 A6 T5 A5 A1
T1 is a taxon with structure A1
A2 descends_from A1 T1
Type level relations are in italics

15. Homologous_to is inferred via descends_from
Two structures are homologous_to each other if they are connected by at least one descends_from triangle.

16. Homologous_to is inferred via descends_from
NOT homologous_to T3 A3
descends_from T8 A8 T6 A2 T2 A6 T5 A5 A1 T1
A6 NOT homologous_to A9 because they do not share a descends_from triangle.

17. Homology example: limb evolution
homologous_to
NOT homologous_to
descends_from

18. Two perspectives for use of homology data
Evolutionary community: Capture homologous_to statements. Calculate descends_from relations, ancestral nodes = phylogenetic optimization.
Model organism databases: Use established descends_from relations to calculate homologous_to relations between structures in different MODs.
ZFIN

19. Outline Current anatomy ontologies (AOs) Standardization CARO Homology
Querying across species

20. Queries for genes in homologous structures
chick
mouse
Niswander, 2003
Development of anatomical homologs may share conserved genetic mechanisms

21. Queries for genes in similar structures
Genetic mechanisms may be reused in similar structures
Structures may be homologous in ways that are yet undetermined
Distal-less (Dll) expression
mouse limb
sea urchin tube feet
Panganiban et al., PNAS, 1997
ascidian ampulla
polychaete parapodia

22. Structural similarity may be related via Xrefs to CARO
Zebrafish AO
is_a
is_a
Xenopus AO

23. Queries for genes in analogous structures
Genetic mechanisms may be reused for similar purposes in analogous structures
Structures may be homologous in ways that are yet undetermined
Vertebrate chambered heart
Process Conserved genes
Specification tinman/nkx2.5, wnts
A-P patterning Hox genes, RA
Morphogenesis Seven-up/Couptf-II
Arthropod dorsal vessel
Xavier-Neto et al., Cell Mol Life Sci, 2007

24. Simultaneous query for homologous, analogous, and structurally similar anatomical entities
UBERON is a grouping ontology inclusive of other AOs
UBERON is highly experimental and was created by:
Xref links between species specific AOs and CARO
Curated mappings
Text-based matching (Obol)
UBERON:inner ear=
FMA: MGI: XAO: ZFA:
ZFIN

25. Homology annotations/mappings

26. Homology annotations/mappings

27. Uberon grouping classes
is_a
is_a
is_a
Cranial nerve VIII

28. UBERON groups anatomical data from different organisms and MODs
UBERON:internal ear groups the following phenotype data:
Species/MOD phenotype
Ostariophysi has character posterior placement lagena
Ostariophysi has character posterior placement saccule
MGI Apoe -/ cochlear inner hair cell degeneration
MGI Dlx5 -/ decreased size lateral semicircular canal
ZFIN stbm -/ increased number otolith organ
ZFIN codjj465/jj decreased size lapillus
OMIM EYA structure Internal ear
OMIM PAX quality Macula lutea
UBERON can be used to identify candidate genes for development, disease or evolution of structures

29. https://lists.sourceforge.net/lists/listinfo/obo-anatomy
Resources
OBO
CARO wiki
Relations wiki
Anatomy listserve
FMA

30. CARO and homology relation participants
Wasila Dahdhul
Paula Mabee
Jose Mejino
Peter Midford
Chris Mungall
Fabian Neuhaus
David Osumi- Sutherland
Allan Ruttenberg
Barry Smith
Did I leave anyone out?
Jason Freeny moistproduction.com