Fisher ME et al. (2022), The Xenopus phenotype ontology: bridging model ...

XB-ART-58865

BMC Bioinformatics 2022 Mar 22;231:99. doi: 10.1186/s12859-022-04636-8.

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The Xenopus phenotype ontology: bridging model organism phenotype data to human health and development.

Segerdell E , Matentzoglu N , Nenni MJ , Fortriede JD , Chu S , Pells TJ , Osumi-Sutherland D , Chaturvedi P , James-Zorn C , Sundararaj N , Lotay VS , Ponferrada V , Wang DZ , Kim E , Agalakov S , Arshinoff BI , Karimi K , Vize PD , Zorn AM .

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BACKGROUND: Ontologies of precisely defined, controlled vocabularies are essential to curate the results of biological experiments such that the data are machine searchable, can be computationally analyzed, and are interoperable across the biomedical research continuum. There is also an increasing need for methods to interrelate phenotypic data easily and accurately from experiments in animal models with human development and disease. RESULTS: Here we present the Xenopus phenotype ontology (XPO) to annotate phenotypic data from experiments in Xenopus, one of the major vertebrate model organisms used to study gene function in development and disease. The XPO implements design patterns from the Unified Phenotype Ontology (uPheno), and the principles outlined by the Open Biological and Biomedical Ontologies (OBO Foundry) to maximize interoperability with other species and facilitate ongoing ontology management. Constructed in Web Ontology Language (OWL) the XPO combines the existing uPheno library of ontology design patterns with additional terms from the Xenopus Anatomy Ontology (XAO), the Phenotype and Trait Ontology (PATO) and the Gene Ontology (GO). The integration of these different ontologies into the XPO enables rich phenotypic curation, whilst the uPheno bridging axioms allows phenotypic data from Xenopus experiments to be related to phenotype data from other model organisms and human disease. Moreover, the simple post-composed uPheno design patterns facilitate ongoing XPO development as the generation of new terms and classes of terms can be substantially automated. CONCLUSIONS: The XPO serves as an example of current best practices to help overcome many of the inherent challenges in harmonizing phenotype data between different species. The XPO currently consists of approximately 22,000 terms and is being used to curate phenotypes by Xenbase, the Xenopus Model Organism Knowledgebase, forming a standardized corpus of genotype-phenotype data that can be directly related to other uPheno compliant resources.

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Species referenced: Xenopus Xenopus tropicalis Xenopus laevis
Genes referenced: xpo1

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	Fig. 1 Workflow diagram for generating and applying a design pattern. Specific manually curated terms are decomposed and used to generate generalized patterns which are matched with existing uPheno design patterns or used for requesting new design patterns. The design patterns are then applied to tabulated sets of XAO, PATO or GO terms to generate new classes of XPO terms
	Fig. 2 The building of an XPO term. XAO terms for phenotypes are selected (1) and entered in TSV files matched to specific design patterns (2). A partial uPheno design pattern YAML file example (3) shows the description of the pattern ‘Abnormally decreased size of anatomical entity’, and templates for generating names, synonyms, definitions, and equivalent classes for the pattern. The ‘%’ characters are substituted with the appropriate terms, in this case ‘anatomical entity’, from the TSV source tables during the ontology building process (4). The pipeline builds the new term from the specified component term and pattern and integrates it into the ontology (5), this shows the built equivalent classes with the XAO term variable filled. Once the new XPO build is complete with the new term it is made available on Xenbase (6)
	Fig. 3 Structural comparison of XAO and XPO. Comparison of graph visualizations of sections of the Xenopus anatomy ontology (XAO) and Xenopus phenotype ontology (XPO). The XPO structure reflects but does not reduplicate that of the XAO as only ‘part-of’ and ‘is_a’ XAO relationships are incorporated and the XPO uses only ‘is_a’ relationships. Consequently, relationships such as ‘develops_from’ are lost. Relationship edges are directed as indicated by arrows
	Fig. 4 Differences between definitions of equivalent classes. Comparison of the equivalent classes for the ‘Unilateral deafness’ phenotype class in the human (HPO) and mammalian (MP) phenotype ontologies
	Fig. 5 Phenotype curation using the XPO on Xenbase. A basic phenotype curation in Xenbase. The record has a brief precis of the experiment, reagents, and assay details, including background Xenopus strain, for the observed phenotypes as well as disease associations
	Fig. 6 Cross species phenotype comparisons through uPheno. An example section of the uPheno2 Unified Phenotype Ontology showing the bridging term for ‘increased size of the heart’ and associated terms from 4 organism or clade specific phenotype ontologies, Xenopus (XPO), Zebrafish (ZP), mammalian (MP) and human (HPO). The common uPheno parent term allows the programmatic inference of phenotypic similarity (yellow dotted arrow) between the terms from differing species, and we can further infer those phenotypes caused by orthologous genes in one model organism species will give rise to similar phenotypes in humans and other species

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Bello, Disease Ontology: improving and unifying disease annotations across species. 2018, Pubmed