Linking MedDRA®-Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors

Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan; Zaman, Shadia; Burkhart, Keith; Omenn, Gilbert S.; He, Yongqun; Athey, Brian D.; Abernethy, Darrell R.

doi:10.1007/s40264-016-0414-0

Cited by 19 publications

(15 citation statements)

References 30 publications

(38 reference statements)

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“…The OAE is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequently to medical interventions (e.g., medication and vaccination), as well as to support computer-assisted reasoning ( He et al, 2014 ). Previous studies have shown that OAE performed well in the analysis of AE data associated with vaccines and drugs ( Sarntivijai et al, 2012 , 2016 ; Xie et al, 2016a , b ). In this study, the OAE was used for representing and classifying the AEs associated with the three brucellosis vaccines in animals and humans.…”

Section: Methodsmentioning

confidence: 96%

Ontology-Based Meta-Analysis of Animal and Human Adverse Events Associated With Licensed Brucellosis Vaccines

Xie

Wang

et al. 2018

Front. Pharmacol.

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Brucella abortus strain 19 (S19), Brucella melitensis Rev 1 (Rev1), and B. abortus strain RB51 (RB51) are the three licensed animal brucellosis vaccines, and they have been most commonly and successfully used in prevent brucellosis in animals. However, many adverse events (AEs) have been associated with these three vaccines after their administering to animals or being accidentally exposed to humans. In this study, 27 peer-reviewed publications containing animal and human AE reports associated with these three brucellosis vaccines were manually annotated from the PubMed database. Our meta-analysis identified 20 animal AEs and 46 human AEs associated with the three vaccines. Based on the Ontology of Adverse Events (OAE) hierarchical classification, these animal AEs were enriched in the immune and reproductive systems that might eventually result in the occurrence of abortion or infertility. The human AEs were concentrated in the behavioral and neurological conditions, and these AEs showed flu-like symptoms that are consistent with human brucellosis. Furthermore, an analysis of variance (ANOVA) statistics analysis with linear model fits was used to determine the major variables that might affect the occurrence of abortion AE in animals. The ANOVA results indicated that three variables (P-value < 0.05) are significantly associated with the occurrence of abortion AE: animal species, vaccination dose, and vaccination route. The other two variables (i.e., vaccine type and animal age at vaccination) did not significantly (P-value > 0.05) associated with the occurrence of abortion AE. Overall, this study represents the first ontology-based meta-analysis of adverse events associated with animal vaccines. The results of such a study led to the better understanding of brucellosis vaccine AEs, facilitating rational design of more secure and effective vaccines.

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Section: Methodsmentioning

confidence: 96%

Ontology-Based Meta-Analysis of Animal and Human Adverse Events Associated With Licensed Brucellosis Vaccines

Xie

Wang

et al. 2018

Front. Pharmacol.

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“…The OAE general framework has been applied to represent and study AEs associated with vaccines in the Ontology of Vaccine Adverse Events (OVAE) [28], neuropathy-inducing drugs in ODNAE [29], and drugs used to treat cardiovascular diseases in OCVDAE [27]. OAE also provides a way to link different domains of entities such as medical administration, anatomic entities, phenotypes, and patient qualities, and cross-reference other controlled terminologies such as the Common Terminology Criteria for Adverse Events (CTCAE) [49] and the Medical Dictionary for Regulatory Activities (MedDRA) [50]. It has become clear that biological ontologies support the integration of biological knowledge for learning and predicting ADEs [51].…”

Section: Discussionmentioning

confidence: 99%

ODAE: Ontology-based systematic representation and analysis of drug adverse events and its usage in study of adverse events given different patient age and disease conditions

Nysak

Garg

et al. 2019

BMC Bioinformatics

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Background Drug adverse events (AEs), or called adverse drug events (ADEs), are ranked one of the leading causes of mortality. The Ontology of Adverse Events (OAE) has been widely used for adverse event AE representation, standardization, and analysis. OAE-based ADE-specific ontologies, including ODNAE for drug-associated neuropathy-inducing AEs and OCVDAE for cardiovascular drug AEs, have also been developed and used. However, these ADE-specific ontologies do not consider the effects of other factors (e.g., age and drug-treated disease) on the outcomes of ADEs. With more ontological studies of ADEs, it is also critical to develop a general purpose ontology for representing ADEs for various types of drugs. Results Our survey of FDA drug package insert documents and other resources for 224 neuropathy-inducing drugs discovered that many drugs (e.g., sirolimus and linezolid) cause different AEs given patients’ age or the diseases treated by the drugs. To logically represent the complex relations among drug, drug ingredient and mechanism of action, AE, age, disease, and other related factors, an ontology design pattern was developed and applied to generate a community-driven open-source Ontology of Drug Adverse Events (ODAE). The ODAE development follows the OBO Foundry ontology development principles (e.g., openness and collaboration). Built on a generalizable ODAE design pattern and extending the OAE and NDF-RT ontology, ODAE has represented various AEs associated with the over 200 neuropathy-inducing drugs given different age and disease conditions. ODAE is now deposited in the Ontobee for browsing and queries. As a demonstration of usage, a SPARQL query of the ODAE knowledge base was developed to identify all the drugs having the mechanisms of ion channel interactions, the diseases treated with the drugs, and AEs after the treatment in adult patients. AE-specific drug class effects were also explored using ODAE and SPARQL. Conclusion ODAE provides a general representation of ADEs given different conditions and can be used for querying scientific questions. ODAE is also a robust knowledge base and platform for semantic and logic representation and study of ADEs of more drugs in the future. Electronic supplementary material The online version of this article (10.1186/s12859-019-2729-1) contains supplementary material, which is available to authorized users.

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“…28 The cardiovascular adverse events associated with 5 TKIs/mAbs, namely, dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab, were extracted from reports in FAERS. This analysis produced 1053 cardiovascular MedDRA terms, of which 884 were unique terms that were not in OAE.…”

Section: Development Of Oae To Capture Adverse Event In An Ontologicamentioning

confidence: 99%

Use of Biomedical Ontologies for Integration of Biological Knowledge for Learning and Prediction of Adverse Drug Reactions

Zaman

Sarntivijai

Abernethy

2017

Gene�Regul Syst Bio

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Drug-induced toxicity is a major public health concern that leads to patient morbidity and mortality. To address this problem, the Food and Drug Administration is working on the PredicTox initiative, a pilot research program on tyrosine kinase inhibitors, to build mechanistic and predictive models for drug-induced toxicity. This program involves integrating data acquired during preclinical studies and clinical trials within pharmaceutical company development programs that they have agreed to put in the public domain and in publicly available biological, pharmacological, and chemical databases. The integration process is accommodated by biomedical ontologies, a set of standardized vocabularies that define terms and logical relationships between them in each vocabulary. We describe a few programs that have used ontologies to address biomedical questions. The PredicTox effort is leveraging the experience gathered from these early initiatives to develop an infrastructure that allows evaluation of the hypothesis that having a mechanistic understanding underlying adverse drug reactions will improve the capacity to understand drug-induced clinical adverse drug reactions.

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Linking MedDRA®-Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors

Cited by 19 publications

References 30 publications

Ontology-Based Meta-Analysis of Animal and Human Adverse Events Associated With Licensed Brucellosis Vaccines

Ontology-Based Meta-Analysis of Animal and Human Adverse Events Associated With Licensed Brucellosis Vaccines

ODAE: Ontology-based systematic representation and analysis of drug adverse events and its usage in study of adverse events given different patient age and disease conditions

Use of Biomedical Ontologies for Integration of Biological Knowledge for Learning and Prediction of Adverse Drug Reactions

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