A gene-phenotype network for the laboratory mouse and its implications for systematic phenotyping.

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 repr...

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Main Authors: Octavio Espinosa, John M Hancock
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0019693&type=printable
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author Octavio Espinosa
John M Hancock
author_facet Octavio Espinosa
John M Hancock
author_sort Octavio Espinosa
collection DOAJ
description 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.
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spelling doaj-art-b816ff4ec797444bbe82e3c59f89f8ac2025-08-20T02:33:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e1969310.1371/journal.pone.0019693A gene-phenotype network for the laboratory mouse and its implications for systematic phenotyping.Octavio EspinosaJohn M HancockThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0019693&type=printable
spellingShingle Octavio Espinosa
John M Hancock
A gene-phenotype network for the laboratory mouse and its implications for systematic phenotyping.
PLoS ONE
title A gene-phenotype network for the laboratory mouse and its implications for systematic phenotyping.
title_full A gene-phenotype network for the laboratory mouse and its implications for systematic phenotyping.
title_fullStr A gene-phenotype network for the laboratory mouse and its implications for systematic phenotyping.
title_full_unstemmed A gene-phenotype network for the laboratory mouse and its implications for systematic phenotyping.
title_short A gene-phenotype network for the laboratory mouse and its implications for systematic phenotyping.
title_sort gene phenotype network for the laboratory mouse and its implications for systematic phenotyping
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0019693&type=printable
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