Gene-Specific Variant Classifier (DPYD-Varifier) to Identify Deleterious Alleles of Dihydropyrimidine Dehydrogenase.
Clin Pharmacol Ther
; 104(4): 709-718, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-29327356
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 are very limited data pertaining to the functional consequences of the >450 reported no-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 unstudied variants, prediction tools like DPYD-Varifier have great potential to individualize medicine and improve the clinical decision-making process.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacogenética
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Simulação por Computador
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Mutação de Sentido Incorreto
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Di-Hidrouracila Desidrogenase (NADP)
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Fluoruracila
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Aprendizado de Máquina
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Testes Farmacogenômicos
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Variantes Farmacogenômicos
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Antimetabólitos Antineoplásicos
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos