Deleterious variants in dihydropyrimidine dehydrogenase (DPD, DPYD gene) can be highly predictive of clinical toxicity to the widely prescribed chemotherapeutic 5-fluorouracil (5-FU). However, there is very limited data pertaining to the functional consequences of the >450 reported non-synonymous DPYD variants. We developed a DPYD-specific variant classifier (DPYD-Varifier) using machine learning and in vitro functional data for 156 missense DPYD variants. The developed model showed 85% accuracy and outperformed other in silico prediction tools. An examination of feature importance within the model provided additional insight into functional aspects of the DPD protein relevant to 5-FU toxicity. In the absence of clinical data for un-studied variants, prediction tools like DPYD-Varifier have great potential to individualize medicine and improve the clinical decision-making process. This article is protected by copyright. All rights reserved.
Pharmacology, Toxicology and Pharmaceutical Science
3
5%
Agricultural and Biological Sciences
2
3%
Engineering
1
2%
Other
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Unknown
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53%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 January 2018.
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