An evidence-based approach to identify aging-related genes in Caenorhabditis elegans

被引:7
作者
Callahan, Alison [1 ]
Cifuentes, Juan Jose [2 ,3 ]
Dumontier, Michel [1 ]
机构
[1] Stanford Univ, Stanford Ctr Biomed Informat Res, Sch Med, Stanford, CA 94305 USA
[2] Millennium Inst Immunol & Immunotherapy, Mol Bioinformat Lab, P-8330025 Santiago, Portugal
[3] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept GenEt Mol & Microbiol, Santiago, Chile
来源
BMC BIOINFORMATICS | 2015年 / 16卷
基金
加拿大自然科学与工程研究理事会;
关键词
Aging; Lifespan; C; elegans; Semantic web; Linked data; SPARQL; SPARQL inferencing notation; Data integration; Hypothesis evaluation; LIFE-SPAN; PROTEIN FUNCTION; SEMANTIC WEB; SIGNALING PATHWAY; KNOWLEDGE; DISEASE; POLYMORPHISMS; ASSOCIATION; GENETICS; BIOINFORMATICS;
D O I
10.1186/s12859-015-0469-4
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页数:18
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