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J Biomed Semantics. 2016 May 21;7:29. doi: 10.1186/s13326-016-0069-x. eCollection 2016.

Ontology-based collection, representation and analysis of drug-associated neuropathy adverse events.

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University of Michigan Medical School, Ann Arbor, MI 48109 USA.
School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203 USA.
Mayo Clinic, Rochester, MN USA.
University of Maryland, Baltimore County, Baltimore, MD 21250 USA.
University of Michigan Medical School, Ann Arbor, MI 48109 USA ; Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, Center for Computational Medicine and Bioinformatics, and Comprehensive Cancer Center, University of Michigan Medical School, 1301 MSRB III, 1150 W. Medical Dr., Ann Arbor, MI 48109 USA.



Neuropathy often occurs following drug treatment such as chemotherapy. Severe instances of neuropathy can result in cessation of life-saving chemotherapy treatment.


To support data representation and analysis of drug-associated neuropathy adverse events (AEs), we developed the Ontology of Drug Neuropathy Adverse Events (ODNAE). ODNAE extends the Ontology of Adverse Events (OAE). Our combinatorial approach identified 215 US FDA-licensed small molecule drugs that induce signs and symptoms of various types of neuropathy. ODNAE imports related drugs from the Drug Ontology (DrON) with their chemical ingredients defined in ChEBI. ODNAE includes 139 drug mechanisms of action from NDF-RT and 186 biological processes represented in the Gene Ontology (GO). In total ODNAE contains 1579 terms. Our analysis of the ODNAE knowledge base shows neuropathy-inducing drugs classified under specific molecular entity groups, especially carbon, pnictogen, chalcogen, and heterocyclic compounds. The carbon drug group includes 127 organic chemical drugs. Thirty nine receptor agonist and antagonist terms were identified, including 4 pairs (31 drugs) of agonists and antagonists that share targets (e.g., adrenergic receptor, dopamine, serotonin, and sex hormone receptor). Many drugs regulate neurological system processes (e.g., negative regulation of dopamine or serotonin uptake). SPARQL scripts were used to query the ODNAE ontology knowledge base.


ODNAE is an effective platform for building a drug-induced neuropathy knowledge base and for analyzing the underlying mechanisms of drug-induced neuropathy. The ODNAE-based methods used in this study can also be extended to the representation and study of other categories of adverse events.

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