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a gene-phenotype network for the laboratory mouse and its implications for systematic phenotypinggene-phenotype网络实验室老鼠及其对系统的影响表现型
A Gene-Phenotype Network for the Laboratory Mouse
and Its Implications for Systematic Phenotyping
1,2¤ 1
Octavio Espinosa , John M. Hancock *
1 Bioinformatics Group, MRC Mammalian Genetics Unit, Harwell, Oxfordshire, United Kingdom, 2 Department of Biochemistry, University of Oxford, Oxford, United
Kingdom
Abstract
The laboratory mouse is the pre-eminent model organism for the dissection of human disease pathways. With the advent of
a comprehensive panel of gene knockouts, projects to characterise the phenotypes of all knockout lines are being initiated.
The range of genotype-phenotype associations can be represented using the Mammalian Phenotype ontology. Using
publicly available data annotated with this ontology we have constructed gene and phenotype networks representing
these associations. These networks show a scale-free, hierarchical and modular character and community structure. They
also exhibit enrichment for gene coexpression, protein-protein interactions and Gene Ontology annotation similarity. Close
association between gene communities and some high-level ontology terms suggests that systematic phenotyping can
provide a direct insight into underlying pathways. However some phenotypes are distributed more diffusely across gene
networks, likely reflecting the pleiotropic roles of many genes. Phenotype communities show a many-to-many relationship
to human disease communities, but stronger overlap at more granular levels of description. This may suggest that
systematic phenotyping projects should aim for high granularity annotations to maximise their relevance to human disease.
Citation: Espinosa O, Hancock JM (2011) A Gene-Phenotype Network for the Laboratory Mouse and Its Implications for Systematic Phenotyping.
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