Unification of multi-species vertebrate anatomy ontologies for comparative biology in Uberon

Abstract

Background: Elucidating disease and developmental dysfunction requires understanding variation in phenotype. Single-species model organism anatomy ontologies (ssAOs) have been established to represent this variation. Multi-species anatomy ontologies (msAOs; vertebrate skeletal, vertebrate homologous, teleost, amphibian AOs) have been developed to represent 'natural' phenotypic variation across species. Our aim has been to integrate ssAOs and msAOs for various purposes, including establishing links between phenotypic variation and candidate genes.

Results: Previously, msAOs contained a mixture of unique and overlapping content. This hampered integration and coordination due to the need to maintain cross-references or inter-ontology equivalence axioms to the ssAOs, or to perform large-scale obsolescence and modular import. Here we present the unification of anatomy ontologies into Uberon, a single ontology resource that enables interoperability among disparate data and research groups. As a consequence, independent development of TAO, VSAO, AAO, and vHOG has been discontinued.

Conclusions: The newly broadened Uberon ontology is a unified cross-taxon resource for metazoans (animals) that has been substantially expanded to include a broad diversity of vertebrate anatomical structures, permitting reasoning across anatomical variation in extinct and extant taxa. Uberon is a core resource that supports single- and cross-species queries for candidate genes using annotations for phenotypes from the systematics, biodiversity, medical, and model organism communities, while also providing entities for logical definitions in the Cell and Gene Ontologies. THE ONTOLOGY RELEASE FILES ASSOCIATED WITH THE ONTOLOGY MERGE DESCRIBED IN THIS MANUSCRIPT ARE AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/2013-02-21/ CURRENT ONTOLOGY RELEASE FILES ARE AVAILABLE ALWAYS AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/

Keywords: Bio-ontology; Evolutionary biology; Morphological variation; Phenotype; Semantic integration.

Figure 1

Enhancement of Uberon with additional content from msAOs. Shown is the representation of ‘pectoral girdle skeleton’ and related classes in Uberon post-merge. Part relations are shown in blue, subclass relations in gray. Classes originally in Uberon have a black outline. The ontology sources of the classes are indicated, as well as one class that was added post-merge in the new Ext file (‘extracleithrum’). Note that some classes were merged from multiple sources, such as the class ‘scapula’, which was in all the sources including Uberon, and ‘appendicular skeleton’, which was in VSAO, AAO, and vHOG but not Uberon or TAO. The classes with more sources are shown in increasingly dark gray.

Figure 2

Overlap and contributions from source ontologies. A) Venn diagram showing the extent of cross-referenced content between msAOs prior to the merge. Note that there are no Xrefs between VSAO and TAO because TAO had obsoleted these classes and replaced them directly with VSAO classes prior to the merge with Uberon. B) Ontology evolution and integration into Uberon. The height of each bar corresponds to the number of classes, the arrows with dotted lines refer to when Xrefs to the source ontologies in Uberon were established. The thick black line refers to cloning (in the case of TAO and ZFA, where 2023 classes from ZFA were used to seed TAO), and the red line to replacement (TAO replaced classes with VSAO classes). Note that TAO, VSAO, AAO, and vHOG are no longer in development following the merge, and their content development will continue in the context of Uberon.

Figure 3

Segments of the hand (here Homo sapiens). In black are skeleton classes, and in red are classes referring to the regions containing those skeletal parts.

Figure 4

Diversity of tooth locations. Both the moray eel (A) and the wolverine mammal (B) have teeth attached to the upper and lower jaw bones; the moray eel also has pharyngeal teeth. This example illustrates the need for a general representation for tooth attachment sites beyond mammal-centric jaw locations.

Figure 5

Decision tree for merging classes from source ontologies into a unified single multi-species Uberon target ontology. The top part of the diagram shows the starting point, with a set of msAOs plus the original version of Uberon (Pre). Each class from the set of msAOs is checked for pre-existing equivalence axioms. If there are no equivalence axioms, a new Uberon class is generated; if there is an equivalence axiom, no new class is generated, but the ontology may be augmented with comments if there are differences in structure (e.g. not isomorphic).

Figure 6

Example of class merges. “E” represents class equivalency. (A) Classes and axioms present in target and sources prior to merge. Note that previously Uberon had no classes for the metapterygoid or its joints. (B) Classes present in target post-merge. TAO and AAO quadrate classes have been merged into the taxonomically equivalent Uberon class, and two new classes are added to Uberon, lifted from TAO. As a separate procedure, all joint axioms are "flipped", with the joints being defined by the elements they are connected to.