A Machine Learning-Based Identification of Genes Affecting the Pharmacokinetics of Tacrolimus Using the DMETTM Plus Platform

Int J Mol Sci. 2020 Apr 4;21(7):2517. doi: 10.3390/ijms21072517.

Abstract

Tacrolimus is an immunosuppressive drug with a narrow therapeutic index and larger interindividual variability. We identified genetic variants to predict tacrolimus exposure in healthy Korean males using machine learning algorithms such as decision tree, random forest, and least absolute shrinkage and selection operator (LASSO) regression. rs776746 (CYP3A5) and rs1137115 (CYP2A6) are single nucleotide polymorphisms (SNPs) that can affect exposure to tacrolimus. A decision tree, when coupled with random forest analysis, is an efficient tool for predicting the exposure to tacrolimus based on genotype. These tools are helpful to determine an individualized dose of tacrolimus.

Keywords: decision tree; genotype; machine learning; random forest; tacrolimus.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Cytochrome P-450 CYP2A6 / genetics*
  • Cytochrome P-450 CYP3A / genetics*
  • Decision Trees
  • Healthy Volunteers
  • Humans
  • Machine Learning
  • Male
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide
  • Precision Medicine
  • Republic of Korea
  • Tacrolimus / pharmacokinetics*
  • Young Adult

Substances

  • 3' Untranslated Regions
  • CYP2A6 protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 CYP3A
  • Tacrolimus