Effective analyses of time trends for post-vaccine adverse events (AEs) can enhance clinical research in different areas such as vaccine safety analyses, causality assessments, and retrospective studies. The FDA/CDC Vaccine Adverse Event Reporting System (VAERS) [1
] provides a valuable data set for these purposes. VAERS maintains a database for reports of AEs following vaccination. These reports contain both structured data (e.g., gender, age, vaccination date, and onset date), as well as short narratives that usually provide more detailed descriptions of the vaccination, the related events, and their time constraints.
The structured data in the VAERS database have been widely leveraged in different medical analyses for vaccine adverse events [2
]. The unstructured nature of the narratives, however, makes the data embedded in them difficult for use in further analyses. These narratives usually contain additional valuable information (e.g., patient ages that were not reported in a structured way, vaccination doses, and durations or time stamps for multiple events following vaccination) that could potentially lead to more effective and concrete clinical analyses, and perhaps important clinical insights.
It is challenging, however, to process this time-related data hidden in the narratives from the AE reports. The VAERS receives 30,000 reports annually. Manually processing these reports is tedious and expensive. Even if the related information has been successfully marked and extracted, the temporal relations needed for time pattern recognition are often not explicitly expressed in the original documents, but rather need to be inferred.
Targeting these challenges, we have designed the Temporal Information Modeling, Extraction, and Reasoning (TIMER) framework for extracting, querying, and inferring useful temporal information automatically. Figure
shows the TIMER system overview. One core component of TIMER is the modeling component. Our vision is to leverage ontologies to semantically model the domain and time knowledge. TIMER relies on the ontologies as the annotation schema for its extraction component, and as the knowledge base for its reasoning component. It is essential to ensure that the ontologies are capable of representing related data faithfully in an integrated, machine-understandable way, so that computer programs can automatically process the data, infer new knowledge, sort clinically relevant events over the timeline, and facilitate data querying for clinical research analyses. In this paper, we introduce our efforts to leverage Semantic Web mechanisms to represent time-related information for vaccine adverse events from the VAERS database. We use the Ontology of Adverse Events (OAE, previously named Ontology of Adverse Event or AEO) [4
] and the Vaccine Ontology (VO) [5
] for representing vaccine names and event names in a standard way. We use the Time Event Ontology (TEO) [6
] to represent the time information among the events.
Previous research indicated that Semantic Web tools and technologies provide a viable solution for modeling of heterogeneous data, conducting scalable querying over the data, and inferring new knowledge [7
]. We believe there are some unique benefits to applying these semantic web techniques to healthcare data: (1) the World Wide Web Consortium (W3C) recommendations provide a shared set of constructs which enable better interoperability between applications that exchange machine-understandable information; (2) the Web Ontology Language (OWL)’s formal semantics offer consistency checking ability for data represented using it; (3) the decidability and computability features of OWL-DL (Description Logic) can provide enough expressiveness for semantically defining concepts and their relationships that can support reasoning; (4) the Rule Interchange Format (RIF) provides a concrete expression language for rules defining clinical guidelines, as well as a standard for the interchanges between rules specified in different rule languages; and (5) the linked data feature of RDF graph can bring information concerning a particular instance together from heterogeneous sources [11
The rest of the paper is organized as follows. We first introduce the three ontologies (TEO, OAE, and VO) and how they can be used to represent time in the area of vaccine adverse events. A VAERS case report is then presented as a use case for the ontological representations. The advantages of using our ontology-based Semantic web representation and data analysis are emphasized. Finally we draw conclusions and discuss further improvements.