PUBLICATION
Phenotype ontologies and cross-species analysis for translational research
- Authors
- Robinson, P.N., Webber, C.
- ID
- ZDB-PUB-140513-215
- Date
- 2014
- Source
- PLoS Genetics 10: e1004268 (Review)
- Registered Authors
- Robinson, Peter N.
- Keywords
- Ontologies, Mouse models, Phenotypes, Animal models of disease, Model organisms, Diagnostic medicine, Schizophrenia, Zebrafish
- MeSH Terms
-
- Animals
- Biological Evolution
- Biological Ontologies*
- Computational Biology/methods*
- Genetic Variation/genetics
- Humans
- Phenotype*
- Translational Research, Biomedical/methods*
- PubMed
- 24699242 Full text @ PLoS Genet.
Citation
Robinson, P.N., Webber, C. (2014) Phenotype ontologies and cross-species analysis for translational research. PLoS Genetics. 10:e1004268.
Abstract
The use of model organisms as tools for the investigation of human genetic variation has significantly and rapidly advanced our understanding of the aetiologies underlying hereditary traits. However, while equivalences in the DNA sequence of two species may be readily inferred through evolutionary models, the identification of equivalence in the phenotypic consequences resulting from comparable genetic variation is far from straightforward, limiting the value of the modelling paradigm. In this review, we provide an overview of the emerging statistical and computational approaches to objectively identify phenotypic equivalence between human and model organisms with examples from the vertebrate models, mouse and zebrafish. Firstly, we discuss enrichment approaches, which deem the most frequent phenotype among the orthologues of a set of genes associated with a common human phenotype as the orthologous phenotype, or phenolog, in the model species. Secondly, we introduce and discuss computational reasoning approaches to identify phenotypic equivalences made possible through the development of intra- and interspecies ontologies. Finally, we consider the particular challenges involved in modelling neuropsychiatric disorders, which illustrate many of the remaining difficulties in developing comprehensive and unequivocal interspecies phenotype mappings.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping