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An evidence-based approach to identify aging-related genes in Caenorhabditis elegans
Authors:Alison Callahan  Juan José Cifuentes  Michel Dumontier
Affiliation:.Stanford Center for Biomedical Informatics Research, School of Medicine, Stanford University, Stanford California, AC USA ;.Molecular Bioinformatics Laboratory, Millennium Institute on Immunology and Immunotherapy, 49 Santiago, CP 8330025 Portugal ;.Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile
Abstract:

Background

Extensive studies have been carried out on Caenorhabditis elegans as a model organism to elucidate mechanisms of aging and the effects of perturbing known aging-related genes on lifespan and behavior. This research has generated large amounts of experimental data that is increasingly difficult to integrate and analyze with existing databases and domain knowledge. To address this challenge, we demonstrate a scalable and effective approach for automatic evidence gathering and evaluation that leverages existing experimental data and literature-curated facts to identify genes involved in aging and lifespan regulation in C. elegans.

Results

We developed a semantic knowledge base for aging by integrating data about C. elegans genes from WormBase with data about 2005 human and model organism genes from GenAge and 149 genes from GenDR, and with the Bio2RDF network of linked data for the life sciences. Using HyQue (a Semantic Web tool for hypothesis-based querying and evaluation) to interrogate this knowledge base, we examined 48,231 C. elegans genes for their role in modulating lifespan and aging. HyQue identified 24 novel but well-supported candidate aging-related genes for further experimental validation.

Conclusions

We use semantic technologies to discover candidate aging genes whose effects on lifespan are not yet well understood. Our customized HyQue system, the aging research knowledge base it operates over, and HyQue evaluations of all C. elegans genes are freely available at http://hyque.semanticscience.org.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-015-0469-4) contains supplementary material, which is available to authorized users.
Keywords:Aging   Lifespan   C. elegans   Semantic web   Linked data   SPARQL   SPARQL inferencing notation   Data integration   Hypothesis evaluation
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