Ontology-Based Vaccine and Drug Adverse Event Representation and Theory-Guided Systematic Causal Network Analysis Toward Integrative Pharmacovigilance Research

Abstract

Compared with controlled terminologies (e.g., MedDRA, CTCAE, and WHO-ART), the community-based Ontology of AEs (OAE) has many advantages in adverse event (AE) classifications. The OAE-derived Ontology of Vaccine AEs (OVAE) and Ontology of Drug Neuropathy AEs (ODNAE) serve as AE knowledge bases and support data integration and analysis. The Immune Response Gene Network Theory explains molecular mechanisms of vaccine-related AEs. The OneNet Theory of Life treats the whole process of a life of an organism as a single complex and dynamic network (i.e., OneNet). A new “OneNet effectiveness” tenet is proposed here to expand the OneNet theory. Derived from the OneNet theory, the author hypothesizes that one human uses one single genotype-rooted mechanism to respond to different vaccinations and drug treatments, and experimentally identified mechanisms are manifestations of the OneNet blueprint mechanism under specific conditions. The theories and ontologies interact together as semantic frameworks to support integrative pharmacovigilance research.

Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis

“…After an AE term mapping between MedDRA and OAE, OAE can be used to classify VAERS reported AEs represented with MedDRA terms [ 15 , 16 ]. Empirical evidences have shown that OAE performs better than MedDRA in the area of AE classification [ 15 , 17 ].…”

Integrative representations and analyses of vaccine-induced intended protective immunity and unintended adverse events using ontology-based and theory-guided approaches

“…More recently, Dr. Yongqun He proposed “the OneNet Theory of Life” [23,24]. The OneNet theory treats the whole process of a life of an individual organism as one single complex and dynamic network (abbreviated as OneNet).…”

“…The OneNet theory treats the whole process of a life of an individual organism as one single complex and dynamic network (abbreviated as OneNet). The OneNet has four characteristics that cover the OneNet Blueprint, OneNet Start, OneNet Dynamics, and OneNet Effectiveness [24]. Compared to the Immune Response Gene Network Theory, the OneNet theory is more focused on the exploration of the root cause of an organism’s phenotypes such as vaccine-induced immune responses and AEs.…”

“…The OneNet theory targets the systematic representation and analysis of the life of one organism (e.g., a human being), with a special focus on the dynamic interactions among genotype, environments, and phenotypes along the life process. Based on the OneNet theory, it is hypothesized that one human uses one single genotype-rooted mechanism ( i.e., OneNet blueprint) to respond to different vaccinations [24]. This hypothesis appears contradictory against obvious experimental observations that human uses different mechanisms against different vaccines.…”

“…This hypothesis appears contradictory against obvious experimental observations that human uses different mechanisms against different vaccines. However, experimentally identified mechanisms are hypothesized to be different manifestations of the same OneNet blueprint mechanism under specific conditions [24]. The introduction of the two concepts, OneNet blueprint and OneNet manifestations, establishes a novel framework that integrates genotypes, environments, and phenotypes under a unified, dynamic, and complex network setting.…”