Authors and contributors:

• Chris Mungall (author)
• Fabian Neuhaus (contributor)
• David Osumi-Sutherland (contributor)
• Melissa Haendel (contributor)
• Frederic Bastian (contributor)

Date: 2012

Document Type: ontology_design_pattern

This document describes how developmental and life cycle stages are represented in Uberon. It is intended for users, ontology developers, and contributing ontologies.

This extends on some of what is described in the section "stages" in the uberon paper

See also: https://github.com/obophenotype/developmental-stage-ontologies/

We have two disjoint hierarchies for stages and structures:

• UBERON:0000000 ! processual entity
  • UBERON:0000105 ! life cycle stage
    • UBERON:0000066 ! fully formed stage
    • UBERON:0000068 ! embryo stage
    • ...
• UBERON:0001062 ! anatomical entity
  • UBERON:0000465 ! material anatomical entity
  • UBERON:0000466 ! immaterial anatomical entity
  • UBERON:0000477 ! anatomical cluster

Note that this means we have different classes for larval stage and larva, with the former representing a division of the timeline and the animal, and the latter representing the actual structure.

To avoid confusion we use strict terminological rules, with all stage classes having a label such as 'X stage', corresponding to a whole-organism structure called 'X'.

We treat these as distinct, although both are subtypes of bfo 'occurrents'. Again this can seem to lead to an increase in the number of terms, as we have both 'gastrulation' (GO) and 'gastrula stage' (Uberon). These are linked by the coincides_with relation from the uberon class.

• GO:0007369 ! gastrulation
• UBERON:0000109 ! gastrula stage

(note: inter-ontology links may not be visible in ontobee)

We use a variety of relationship types for connecting stages to eachother, and for connecting stages to structures. These relations are based on work by Fabian Neuhaus and David Osumi-Sutherland and will be described in more detail in a subsequent publication. A brief overview is provided here.

Stages are subdivided using the BFO:0000050 part of relation. Each stage always has at least one subclass axiom (isa parent). This is typically to the parent life cycle stage.

Stages are ordered in succession via the immediately preceded by relation when we know there are no intervening stages. In a general ontology like Uberon way sometimes want to be more open, e.g.

An adult stage is always preceded by an embryonic stage - we can only say immediately preceded when we are talking about specific taxa, e.g amniotes (in other taxa there may be intervening larvals stages)

The core distinction is between embryonic stages and post-embryonic stages. In some animals there are other stages such as larval.

The early development stages in Uberon are taken from BILA and describe a typical sequence of development found across metazoa, up until gastrulation

TODO - Documentation will be added here later

Uberon uses sexual maturoty as the core developmental landmark. This leads to a slight disjunction between terminology applied to humans and other animals. We are working on the best way to resolve these.

TODO - Documentation will be added here later

We may use the NIFSTD subdivisions developed by Bill Bug here, but this may better be treated in a dedidcated human staging ontology

As a general rules, Uberon leaves species-specific classes to dedicated species ontologies. The ontologies together form a federation, which can be consumed either via composite or importer ontologies (see ADD LINK HERE).

Staging schemes are typically devised for a specific species (and often a stereotypical member of that species), and thus fall outside the purview of Uberon core. We provide some rules for species anatomy developers to assist the federation process.

In order of preferences, stage ontologies should:

• be logically consistent with core uberon generic stages
• use identifiers that are conformant to OBO guidelines
• isa-complete
• uses isa vs part_of in the correct way
• be openly released at a reasonable frequence, and be resposibe to reasonable requests
• uses intermediate subdivisions where appropriate (ie isn't a flat list)
• uses preceded_by relationships to create a temporal ordering - this should be a total order on the leaf nodes
• use standard naming conventions
• names stages such that they won't be confused with corresponding structures (e.g. 'embryo stage' vs embryo)
• includes numeric timing info using OWL datatypes (e.g. has_day 23^^xsd:int)

Currently it is difficult to federate mammalian staging ontologies, we are working on solutions here.

There may be more than one overlapping staging scheme for an organism. Currently these are not represented in Uberon, or in any of the federated ontologies. If there is demand for these, we would be willing to work with federated ontologies in capturing this knowledge.

As mentioned previously, staging schemes are species specific. Even within the mammals, once gastrulation is over we do not break down the embryonic stage into more refined pan-mammalian stages.

It may be possible to align Carnegie stages and Thelier stages at a higher level of granularity. We have no immediate plans to do this, but users interested in an automated approach to this should consult Aitken at el (TODO: PMID).

Staging schemes can be applied to anatomical structures as well as the whole organism - for example, limb staging. It is not clear the situations where this helps, given that we may already have the structures themselves subtypes (e.g. limb bud vs limb) and the devlopmental processes may be described in GO. The GO cell cycle subset can also be considered to be redundant with a staging ontology for cell types.

Currently (Jan 2013) we do not have non-life cycle stages in Uberon, but this may change in the future.

The FBdv ontology contains some good examples of stages for anatomical structures.

The stages in uberon are available as a separate subset ontology (TODO: add link)

The backbone of the Uberon staging system was lifted directly from BILA. Future development was done in collaboration with the Bgee group. We also made use of the XUO ontology developed by Stuart Aitken.