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Knowledge graph prediction of unknown adverse drug reactions and validation in electronic health records

Bean, DM; Wu, H; Dzahini, O; Broadbent, M; Stewart, R; Dobson, RJB; (2017) Knowledge graph prediction of unknown adverse drug reactions and validation in electronic health records. Scientific Reports , 7 , Article 16416. 10.1038/s41598-017-16674-x. Green open access

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Abstract

Unknown adverse reactions to drugs available on the market present a significant health risk and limit accurate judgement of the cost/benefit trade-off for medications. Machine learning has the potential to predict unknown adverse reactions from current knowledge. We constructed a knowledge graph containing four types of node: drugs, protein targets, indications and adverse reactions. Using this graph, we developed a machine learning algorithm based on a simple enrichment test and first demonstrated this method performs extremely well at classifying known causes of adverse reactions (AUC 0.92). A cross validation scheme in which 10% of drug-adverse reaction edges were systematically deleted per fold showed that the method correctly predicts 68% of the deleted edges on average. Next, a subset of adverse reactions that could be reliably detected in anonymised electronic health records from South London and Maudsley NHS Foundation Trust were used to validate predictions from the model that are not currently known in public databases. High-confidence predictions were validated in electronic records significantly more frequently than random models, and outperformed standard methods (logistic regression, decision trees and support vector machines). This approach has the potential to improve patient safety by predicting adverse reactions that were not observed during randomised trials.

Type: Article
Title: Knowledge graph prediction of unknown adverse drug reactions and validation in electronic health records
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-017-16674-x
Publisher version: https://doi.org/10.1038/s41598-017-16674-x
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Data integration, Drug safety, Machine learning
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10040591
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