The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and analyzing adverse events associated with US-licensed human vaccines

BackgroundLicensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO).ResultsLike OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term ‘human vaccinee population’ is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed.ConclusionsThe ontology-based data representation and integration using the FDA-approved information from the vaccine package insert documents enables the identification of adverse events from vaccination in relation to predefined parts of the population (age groups) and certain groups of vaccines. The resulting ontology-based VAE knowledge base classifies vaccine-specific VAEs and supports better VAE understanding and future rational AE prevention and treatment.

[1]  Yu Lin,et al.  Ontorat web server for automatic generation and annotations of new ontology terms , 2012, ICBO.

[2]  G. Omenn,et al.  Ontology-Based Combinatorial Comparative Analysis of Adverse Events Associated with Killed and Live Influenza Vaccines , 2012, PloS one.

[3]  E. Brown,et al.  Methods and Pitfalls in Searching Drug Safety Databases Utilising the Medical Dictionary for Regulatory Activities (MedDRA)1 , 2003, Drug safety.

[4]  Yu Lin,et al.  Ontology representation and analysis of vaccine formulation and administration and their effects on vaccine immune responses , 2012, Journal of Biomedical Semantics.

[5]  Ryan R Brinkman,et al.  OntoFox: web-based support for ontology reuse , 2010, BMC Research Notes.

[6]  Jessica A. Turner,et al.  Modeling biomedical experimental processes with OBI , 2010, J. Biomed. Semant..

[7]  M. Ashburner,et al.  The OBO Foundry: coordinated evolution of ontologies to support biomedical data integration , 2007, Nature Biotechnology.

[8]  Dragomir R. Radev,et al.  Mining of vaccine-associated IFN-γ gene interaction networks using the Vaccine Ontology , 2011, J. Biomed. Semant..

[9]  Bjoern Peters,et al.  VO: Vaccine Ontology , 2009 .

[10]  E. Brown,et al.  The Medical Dictionary for Regulatory Activities (MedDRA) , 1999, Drug safety.

[11]  Markus Krötzsch,et al.  ELK Reasoner: Architecture and Evaluation , 2012, ORE.

[12]  Alan Ruttenberg,et al.  Ontobee: A Linked Data Server and Browser for Ontology Terms , 2011, ICBO.

[13]  J. Dórea,et al.  Vaccine Adverse Events Reported during the First Ten Years (1998–2008) after Introduction in the State of Rondonia, Brazil , 2013, BioMed research international.

[14]  Fang Chen,et al.  VIOLIN: vaccine investigation and online information network , 2007, Nucleic Acids Res..

[15]  Werner Ceusters,et al.  AEO: A Realism-Based Biomedical Ontology for the Representation of Adverse Events , 2011, ICBO.

[16]  Robert T. Chen,et al.  Understanding vaccine safety information from the Vaccine Adverse Event Reporting System. , 2004, The Pediatric infectious disease journal.