Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients.

Journal: Scientific reports
PMID:

Abstract

Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the "derivation cohort" to develop dose-prediction algorithm, while the remaining 20% constituted the "validation cohort" to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67-0.76)] and validation cohorts [0.73 (0.63-0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

Authors

  • Jie Tang
    Department of Computer Science and Technology, Tsinghua University, Beijing, China jietang@tsinghua.edu.cn.
  • Rong Liu
    School of Biomedical Engineering, Dalian University of Technology, Dalian, China.
  • Yue-Li Zhang
    Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.
  • Mou-Ze Liu
    Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.
  • Yong-Fang Hu
    Peking University Third Hospital, Beijing, 100191, P. R. China.
  • Ming-Jie Shao
    Research Center of Chinese Health Ministry of Transplantation Medicine Engineering and Technology, Third Affiliated Hospital, Central South University, Changsha, 410013, Hunan, P. R. China.
  • Li-Jun Zhu
    Research Center of Chinese Health Ministry of Transplantation Medicine Engineering and Technology, Third Affiliated Hospital, Central South University, Changsha, 410013, Hunan, P. R. China.
  • Hua-Wen Xin
    Department of Clinical Pharmacology, Wuhan General Hospital of Guangzhou Command, Wuhan, 430070, Hubei, P. R. China.
  • Gui-Wen Feng
    Department of Renal Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, P. R. China.
  • Wen-Jun Shang
    Department of Renal Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, P. R. China.
  • Xiang-Guang Meng
    School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, P. R. China.
  • Li-Rong Zhang
    School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, P. R. China.
  • Ying-Zi Ming
    Research Center of Chinese Health Ministry of Transplantation Medicine Engineering and Technology, Third Affiliated Hospital, Central South University, Changsha, 410013, Hunan, P. R. China.
  • Wei Zhang
    The First Affiliated Hospital of Nanchang University, Nanchang, China.