More than one way to dissect an animal Melissa Haendel ZFIN Scientific Curator

Model organism databases (MODs) use anatomy ontologies for annotation pax3 expression in forelimb bud and somites (Houzelstein et.al, 1999) pax2a expression in midbrain hindbrain boundary and pronephric duct (Thisse et.al, 2001) Segmentation stage: somites ama expression in tracheal system, lateral cord Stages: (Seeger et al., 1988) Stage: 29 somites fruitfly zebrafish mouse

Why do MODs use anatomy ontologies vs. a simple constrained vocabulary? Ontologies facilitate grouping of annotations: brain 20 hindbrain 15 rhombomere 10 If MODs construct their anatomy ontologies using the same principles they will be better able to reason across species Query brain without ontology 20 Query brain with ontology 45

Most developmental anatomy ontologies have multiple axes of classification Functional: cardiovascular system, nervous system Spatial: head, trunk, limb Developmental: endoderm, germ ring, lens placode Structural: tissue, organ, cell Stage: developmental staging series  Terms are often arranged spatially or by function for ease of browsing or editing  Developmental terms are often lumped together for lack of a way to categorize them  Stages are represented in a variety of ways. Terms can be children of superstages, stages can be integrated into each term, or stages can be assigned to terms from a separate ontology How can CARO unify this organization?

What relationships are being used in developmental anatomy ontologies?  is_a: classification of structures  part_of: classical anatomical partonomy  develops_from: a one to one, one to many, or many to one relationship describing the temporal lineage of anatomical structures

Different MODs have built their anatomy ontologies differently zebrafish mouse fruitfly

Three different levels of anatomical granularity Cross-species subcellular anatomy (GO CC) Cross-species cellular anatomy (CL) Species-specific gross anatomy (ZFA) Can CARO integrate these anatomy ontologies?

 Stages may have defining morphological characteristics or be fiat in time What are developmental stages? (After Haeckel, from Romanes, 1901)  There are different staging series for different organisms Zebrafish bud stage; 10 – 10.3 hpf  A stage represents a period of time

How can stages be represented in a developmental anatomy ontology? Stage A (1-2 hrs) Stage B (2-3 hrs) Stage C (3-4 hrs) : Each anatomical structure has a stage range during which it exists Anatomical structure X begins during stage A is apparent until stage C

How are the hierarchical relationships between terms affected by stage assignments? A child must exist within the stage range of its parent. A child’s stage range must overlap or abut the stage range of its parent. develops_from is_a part_of brain 1-5 hindbrain 2-5 rhombomere 3-4 ganglion 1-5 cranial ganglion 3-5 trigeminal ganglion 4-5 facial ganglion 3-5 neural plate 1-3 neural tube 3-4 spinal cord 4-6 is_a develops_from part_of biological intuition suggests:

Why do we need CARO?  To facilitate cross-species queries, for example, similar phenotypes or gene expression  To help MODs build anatomy ontologies for better curation and query  To promote better data-mining within and between ontologies i.e. species-specific anatomy, cellular and sub- cellular anatomy, processes, functions, stages, taxonomy

Points of discussion 1. Are the relationships is_a, part_of, and develops_ from sufficient for our needs? Develops_from has not yet been finalized in OBO-REL. What other relationships are required? 2. How should the MODs and/or CARO integrate the three ontological granularities of anatomy represented thus far? 3. The human foundational model of anatomy (FMA) is a structural ontology which offers many advantages. Can CARO integrate the functional, spatial, developmental, and staged anatomy? 4. How many stage relationships are needed? How should they be defined? How will they be used? 5. How organismally diverse should CARO be? 6. How deep should CARO be? WE NEED USE CASES