J Biomed Semantics
October 18, 2013;
Enhanced XAO: the ontology of Xenopus anatomy and development underpins more accurate annotation of gene expression and queries on Xenbase.
The African clawed frogs Xenopus laevis and Xenopus tropicalis are prominent animal model organisms. Xenopus research contributes to the understanding of genetic, developmental and molecular mechanisms underlying human disease. The Xenopus Anatomy Ontology (XAO) reflects the anatomy and embryological development of Xenopus. The XAO provides consistent terminology that can be applied to anatomical feature descriptions along with a set of relationships that indicate how each anatomical entity is related to others in the embryo
, or adult frog
. The XAO is integral to the functionality of Xenbase (http://www.xenbase.org), the Xenopus model organism database. We significantly expanded the XAO in the last five years by adding 612 anatomical terms, 2934 relationships between them, 640 synonyms, and 547 ontology cross-references. Each term now has a definition, so database users and curators can be certain they are selecting the correct term when specifying an anatomical entity. With developmental timing information now asserted for every anatomical term, the ontology provides internal checks that ensure high-quality gene expression and phenotype data annotation. The XAO, now with 1313 defined anatomical and developmental stage terms, has been integrated with Xenbase expression and anatomy term searches and it enables links between various data types including images, clones, and publications. Improvements to the XAO structure and anatomical definitions have also enhanced cross-references to anatomy ontologies of other model organisms and humans, providing a bridge between Xenopus data and other vertebrates. The ontology is free and open to all users. The expanded and improved XAO allows enhanced capture of Xenopus research data and aids mechanisms for performing complex retrieval and analysis of gene expression, phenotypes, and antibodies through text-matching and manual curation. Its comprehensive references to ontologies across taxa help integrate these data for human disease modeling.
J Biomed Semantics
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Figure 1. Growth of the xenopus anatomy ontology. In the course of its major public releases since 2008, the number of terms in the ontology has grown by 87% and the number of part_of and develops_from relationships has substantially increased. The majority of terms in the initial release lacked definitions and is_a parents, while the latest release (October 9, 2013) is definition- and is_a-complete.
Figure 2. Inter-relationships of pronephric kidney tissues and structures, their developmental timing, and curated data. A. The developmental timing of a Xenopus anatomical entity (blue fill) is asserted by starts_during and ends_during relationships to specific embryonic stages (green fill), demonstrated here by the 'pronephric kidney�(yellow fill). B. Ontological assertions about developmental timing place constraints on data curation. Expression of the gene slc12a1 in a NF stage 37/38 embryo (assayed by fluorescent in situ hybridization; XB-IMG-2158) is evident in 'early distal tubule�. C. Expression of slc5a1.2 in a NF stage 37/38 embryo (assayed via in situ hybridization; XB-IMG-2348) is recorded by curators as taking place in the 'early proximal tubule� and 'late proximal tubule�. Intermediate NF stages have been omitted for simplicity. Relationship types (colored arrows): is_a (black), part_of (blue), develops_from (purple), starts_during (green), ends_during (red), preceded_by (orange). Images (B) by P. Vize, and (C) by Zhou & Vize , used with permission, �Elsevier (2004).
Figure 3. Links from the Xenopus Anatomy Ontology to Xenopus data in Xenbase. The XAO search anatomy items function returns the exact match on the query term 'heart�. In addition, anatomy features such as 'cardiac mesoderm� that have relationships to 'heart� in the ontology are also returned. Clicking on any term takes users to an XAO term summary page. The Expression tab on the 'heart� term page has links to data related to 4520 expressed genes. Shown schematically is a sample of genes (green fill) that most frequently appear in each of three principal data categories (images, clones, papers: indicated by solid lines). nkx2-5 expression appears in the greatest number of Xenbase images and is cited in the most publications. The gene acta1 is associated with the most clones from heart tissue. The genes actc1, myl3 and acta1 (bold outline) are associated with the greatest combined number of records as of May 20, 2013. The total number of records in each data category for all heart-expressed genes is shown. Heart image by Kolker, Tajchman & Weeks , used with permission, �Elsevier (2000).
Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.