Uberon, an integrative multi-species anatomy ontology

Abstract

We present Uberon, an integrated cross-species ontology consisting of over 6,500 classes representing a variety of anatomical entities, organized according to traditional anatomical classification criteria. The ontology represents structures in a species-neutral way and includes extensive associations to existing species-centric anatomical ontologies, allowing integration of model organism and human data. Uberon provides a necessary bridge between anatomical structures in different taxa for cross-species inference. It uses novel methods for representing taxonomic variation, and has proved to be essential for translational phenotype analyses. Uberon is available at http://uberon.org.

Figure 1

Uberon integrates anatomical ontologies. Anatomical representation of 'lung' and related types and processes are siloed in various ontologies with no connections. EHDAA/EHDAA2, Edinburgh Human Developmental Anatomy, abstract version/abstract version 2; FMA, Foundational Model of Anatomy; GO, Gene Ontology; MA, Mouse Anatomy Ontology; MPO, Mammalian Phenotype Ontology.

Figure 2

Illustration of how Uberon relates anatomical silos into a unified view. Uberon classes are shown in gray and classes from external ontologies are indicated with their respective prefix. Classes in light gray have computable definitions, which are indicated by the relations shown. For example, 'alveolus of lung' is_a 'alveolus' that is part_of some 'lung'. 'Respiration organ' is_a organ that is capable_of GO:respiratory gaseous exchange. The blue circle indicates what would be included in a mammal-restricted subset of Uberon, as swim bladder is not found in mammals. Use of Uberon together with taxon-specific anatomy ontologies enables bridging of the data with full reasoning capabilities. In this example, Uberon 'lung' subsumes the lung classes from the mouse and human anatomy ontologies. Classes in the blue circle plus the blue classes at the bottom would be available in uberon-collected-mammal.owl. Note that some relationships have been trimmed for illustration purposes.

Figure 3

Import chain of taxonomically arranged Uberon modules. Each combined module at different taxonomic levels imports the relevant native ontologies as well as bridge files that specify the logical definitions. The number of equivalent class (EC) or SubClass (SC) axioms in each bridge file are shown, illustrating the contributions of each ontology to the total infrastructure. The files linked with dotted lines represent the mechanism by which a new chicken anatomy ontology (and similarly, archosaur) would be integrated.

Figure 4

Strategy for applying taxonomic constraints. If the fruitfly class FBbt:tibia (representing a segment of an insect leg) were accidentally placed as a child of UBERON:0000979 'tibia', the reasoner would flag this as an error because 'tibia' is_a 'bone' in Uberon, bones are found only in vertebrates, and FBbt:tibia is a Drosophila structure.

Figure 5

Expression of Distal-less (Dll) and Dll orthologs (Dlx) in 'legs'. (a) Three-day Molgula occidentalis ascidian larva from which an ampulla is extending. (b) Polychaete annelid Chaetopterus variopedatus, ventral view of larva just prior to metamorphosis (anterior to left). Dll expressing cells are visible in parapodial rudiments (arrows), antennae (out of focus on opposite dorsal surface), and in prospective feeding organs (bracket). (c) Metamorphosing Strongylocentrotus droebachiensis sea urchin larvae, aboral view. Cells at the distal tip of the tube feet (arrows) express Dll prior to and during extension from the body wall. (d) Expression in nine-day mouse embryo, lateral view, head top; arrows point to medial border of cells expressing one or more Dlx genes in the presumptive forelimb. (e) The evolutionary appearance of the various appendages for which Dll expression data are indicated in (a-d) are shown on this cladogram (branch lengths are not scaled). Reprinted with modification and permission from [49].