ArticleDrug safety2016
Linking MedDRA(®)-Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors.
Article in Drug safety, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Computational Advances in Drug Safety: Systematic and Mapping Review of Knowledge Engineering Based Approaches.Frontiers in pharmacology · 2019Pooled it
- Pooled it
- The Ontology of Adverse Events in 2025.Scientific data · 2026Article
- Aggregation of Adverse Event Terms for Signal Detection and Labeling in Clinical Trials.Drug safety · 2025Article
- Unraveling the mechanisms of irAEs in endometrial cancer immunotherapy: insights from FAERS and scRNA-seq data.Scientific reports · 2025Article
- COVID-19 vaccine design using reverse and structural vaccinology, ontology-based literature mining and machine learning.Briefings in bioinformatics · 2022Article
- Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on spontaneous reports in FAERS.Frontiers in pharmacology · 2022Article
- Ontology-Based Classification and Analysis of Adverse Events Associated With the Usage of Chloroquine and Hydroxychloroquine.Frontiers in pharmacology · 2022Article
- Hepatotoxicity reports in the FDA adverse event reporting system database: A comparison of drugs that cause injuryActa pharmaceutica Sinica. B · 2021Article
- Auto-Generated Physiological Chain Data for an Ontological Framework for Pharmacology and Mechanism of Action to Determine Suspected Drugs in Cases of Dysuria.Drug safety · 2019Article
- 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.BMC bioinformatics · 2019Article
- Study of serious adverse drug reactions using FDA-approved drug labeling and MedDRA.BMC bioinformatics · 2019Article
- AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2018Article
- Ontology-Based Meta-Analysis of Animal and Human Adverse Events Associated With Licensed Brucellosis Vaccines.Frontiers in pharmacology · 2018Article
- Ontology-based systematical representation and drug class effect analysis of package insert-reported adverse events associated with cardiovascular drugs used in China.Scientific reports · 2017Article
- Use of Biomedical Ontologies for Integration of Biological Knowledge for Learning and Prediction of Adverse Drug Reactions.Gene regulation and systems biology · 2017Review
- Statistical and Ontological Analysis of Adverse Events Associated with Monovalent and Combination Vaccines against Hepatitis A and B Diseases.Scientific reports · 2016Article
- Integrative representations and analyses of vaccine-induced intended protective immunity and unintended adverse events using ontology-based and theory-guided approaches.Global vaccines and immunology · 2016Article
- Ontology-based collection, representation and analysis of drug-associated neuropathy adverse events.Journal of biomedical semantics · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
introductionA translational bioinformatics challenge exists in connecting population and individual clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA(®)) is the default dictionary for adverse event (AE) reporting in the US Food and Drug Administration Adverse Event Reporting System (FAERS). The ontology of adverse events (OAE) represents AEs as pathological processes occurring after drug exposures.
objectivesThe aim of this work was to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA(®) in FAERS data analysis. We investigated the AEs associated with tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The five selected TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity.
resultsStatistical analysis of FAERS data identified 1053 distinct MedDRA(®) terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA(®). The data integration to provide insights into molecular mechanisms of drug-associated AEs was performed by including linkages in OAE for all related AE terms to MedDRA(®) and the existing ontologies, including the human phenotype ontology (HP), Uber anatomy ontology (UBERON), and gene ontology (GO). Sixteen AEs were shared by all five TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed "cardiac failure" using the relations established in OAE with other ontologies and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction.
conclusionBy expanding the existing OAE ontological design, our TKI use case demonstrated that the combination of OAE and MedDRA(®) provides a semantic framework to link clinical phenotypes of adverse drug events to biological mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.