A new ontology (structured hierarchy) of human developmental anatomy for the first 7 weeks (Carnegie stages 1-20)

Abstract

This paper describes a new ontology of human developmental anatomy covering the first 49 days [Carnegie stages (CS)1-20], primarily structured around the parts of organ systems and their development. The ontology includes more than 2000 anatomical entities (AEs) that range from the whole embryo, through organ systems and organ parts down to simple or leaf tissues (groups of cells with the same morphological phenotype), as well as features such as cavities. Each AE has assigned to it a set of facts of the form <AE><relationship><parent>, with the relationships including starts_at and ends_at (CSs), part_of (there can be several parents) and is_a (this gives the type of tissue, from an organ system down to one of ~ 80 simple tissues predominantly composed of a single cell kind, which is also specified). Leaf tissues also have a develops_from link to its parent tissue. The ontology includes ~14 000 such facts, which are mainly from the literature and an earlier ontology of human developmental anatomy (EHDAA, now withdrawn). The relationships enable these facts to be integrated into a single, complex hierarchy (or mathematical graph) that was made and can be viewed in the OBO-Edit browser (oboedit.org). Each AE has an EHDAA2 ID that may be useful in an informatics context, while the ontology as a whole can be used for organizing databases of human development. It is also a knowledge resource: a user can trace the lineage of any tissue back to the egg, study the changes in cell phenotype that occur as a tissue develops, and use the structure to add further (e.g. molecular) information. The ontology may be downloaded from www.obofoundry.org. Queries and corrections should be sent to j.bard@ed.ac.uk.

Fig. 1

An OBO-Edit screen shot showing the ontology tree editor (the EHDAA2 hierarchy), the search panel (choice = epiblast) and the Parent Editor (showing all the parents of epiblast and their relationships). The ontology shows the top-level partonomy to display how the anatomy is laid out; the organ system group and the embryonic membranes have been expanded to show the next level of parts.

Fig. 2

The neural crest lineage in EHDAA2. OBO-Edit shows the develops_from relationship as a white D in a dark blue diamond. See Table 1 for an example of the full details for a neural crest derivative.

Fig. 3

An OBO-Edit screen shot showing features of the heart partonomy. In the lower part of the picture, the primitive heart tube gives the early tissues; the upper part includes the hierarchies for the endocardium and the myocardium.

Fig. 4

The components of the rhombencephalon and early hindbrain show, in particular, the development of pro-rhombomeres (CS9–11) to early rhombomeres (CS12–13) in the rhombencephalon, to mature rhombomeres (CS14–15) in the future myelencephalon and metencephalon. The different names are needed because ontologies require time-dependent tissues to be distinguishable.

Fig. 5

OBO-Edit screen shots of the classification hierarchy. (a) the ganglia; (b) the neuronal nuclei. The Parent Editor shows the timing and other relationships for each of these tissues in another window.