Dahdul WM et al. (2012), A unified anatomy ontology of the vertebrate sk...

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PLoS One 2012 Jan 01;712:e51070. doi: 10.1371/journal.pone.0051070.

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A unified anatomy ontology of the vertebrate skeletal system.

Dahdul WM , Balhoff JP , Blackburn DC , Diehl AD , Haendel MA , Hall BK , Lapp H , Lundberg JG , Mungall CJ , Ringwald M , Segerdell E , Van Slyke CE , Vickaryous MK , Westerfield M , Mabee PM .

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The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

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Species referenced: Xenopus
Genes referenced: acta4 gnao1

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	Figure 2. Some skeletogenic cells and their relationships to other cells and skeletal tissues.CL terms are shown in yellow fill, VSAO tissue terms in grey fill.
	Figure 3. Some skeletal tissues in the VSAO and selected relationships to other tissues, cells, and skeletal elements.CL terms are shown in yellow fill, tissue terms in grey fill, skeletal element terms in blue fill, and skeletal subdivision terms in green fill.
	Figure 4. Representation of the skeleton in vertebrate anatomy ontologies.The vertebrate skeleton can be partitioned according to many different criteria â and it had been by the different groups (Table 1) that developed anatomy ontologies. For example (A), âboneâ had been treated as a type of tissue by all except the MA, who also related it to the concept of âbone organâ. In the VSAO (B), the concepts of bone tissue and bone element were disentangled, named and defined. Individual bone elements were related to their tissue and cell components as well as developmental processes. From these links one can reason that, e.g., the âfemurâ is part_of âendoskeletonâ, develops_from âcartilage elementâ, and participates_in the process of âendochondral ossificationâ, whereas the âfrontal boneâ is part_of âdermal skeletonâ and participates_in the process of âdirect ossificationâ. Image on left shows chondrocytes embedded in a bone matrix developed from periosteum of fractured chick dermal bone. Image on right shows a late gestational stage mouse embryo stained with alcian blue and alizarin red. CL term is shown in yellow fill, tissue terms in grey fill, skeletal element terms in blue fill, and skeletal subdivision terms in green fill. Parent classes from CARO are in red font, GO terms in green font, TAO terms in blue font, and VSAO terms in black font.
	Figure 5. Some skeletal subdivisions and their relationships in the VSAO.CARO parent term is in red font and VSAO terms in black font.
	Figure 6. Representation of a skeletal element with multiple classification criteria.The âtripusâ is directly asserted (solid lines) to be a type of âendochondral boneâ, part_of the âWeberian ossicle setâ, part_of âvertebra 3â² and to form through the process of (âparticipates_inâ) âintramembranous ossificationâ. The reasoner infers (dotted lines) the tripus to be a type of âmembrane boneâ and a âWeberian ossicleâ, and infers it to participate in âendochondral ossificationâ. Skeletal element terms are shown in blue fill, skeletal subdivision term in green fill, TAO terms in blue font, VSAO terms in black font, and GO process terms in green font.
	Figure 1. Four high-level classes of skeletal anatomy (â€˜cellâ€™, â€˜skeletal tissueâ€™, â€˜skeletal elementâ€™, â€˜skeletal subdivisionâ€™) and their children based on anatomical granularity.Cell terms (CL) are shown in yellow fill, tissue terms in grey fill, skeletal element terms in blue fill, and skeletal subdivision terms in green fill. Parent classes from CARO in red font. Alligator mississippiensis sectioned maxilla (âˆ¼day 27 in ovo; Ferguson stage 19) stained with Mallory's trichrome (A); midsagittally sectioned embryonic head (day 45 in ovo; Ferguson stage 23) in lateral (B) and saggital (C) view, double stained whole-mount (alizarin red and alcian blue).

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