Identifying aberrant pathways through integrated analysis of knowledge in pharmacogenomics
Identifying aberrant pathways through integrated analysis of knowledge in pharmacogenomics
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DOI：
10.1093/bioinformatics/bts350
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发表时间：
2012-08-15
期刊：
影响因子：
5.8
通讯作者：
Gkoutos, Georgios V.
中科院分区：
文献类型：
--
作者：
Hoehndorf, Robert;Dumontier, Michel;Gkoutos, Georgios V.
动机：许多复杂疾病是通路功能异常的结果，而不是单一异常。疾病诊断和干预策略必须针对这些途径，同时尽量减少对正常生理过程的干扰。大规模确定疾病途径和可能用于干扰它们的化学物质需要整合有关药物、基因、疾病和途径的信息。这些信息目前分布在几个药物基因组学数据库中。在这些数据库中的信息的综合分析可以揭示疾病的途径和促进新的生物医学analysis.Results：我们演示了如何整合药物基因组学数据库，通过整合的生物医学本体，在这些数据库中作为元数据。这些本体中的附加背景知识然后可以用于实现新颖的分析。我们使用一种新的多本体富集分析在人类疾病本体识别疾病途径，我们确定显着的化学物质和途径之间的关联使用富集分析在化学本体。药物-通路和疾病-通路关联是疾病和药物机制研究的宝贵资源，可用于改善计算药物再利用。
Motivation: Many complex diseases are the result of abnormal pathway functions instead of single abnormalities. Disease diagnosis and intervention strategies must target these pathways while minimizing the interference with normal physiological processes. Large-scale identification of disease pathways and chemicals that may be used to perturb them requires the integration of information about drugs, genes, diseases and pathways. This information is currently distributed over several pharmacogenomics databases. An integrated analysis of the information in these databases can reveal disease pathways and facilitate novel biomedical analyses.Results: We demonstrate how to integrate pharmacogenomics databases through integration of the biomedical ontologies that are used as meta-data in these databases. The additional background knowledge in these ontologies can then be used to enable novel analyses. We identify disease pathways using a novel multi-ontology enrichment analysis over the Human Disease Ontology, and we identify significant associations between chemicals and pathways using an enrichment analysis over a chemical ontology. The drug-pathway and disease-pathway associations are a valuable resource for research in disease and drug mechanisms and can be used to improve computational drug repurposing.