Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy.

Journal: Archives of toxicology
PMID:

Abstract

Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.

Authors

  • Hongying Ma
    Department of Pharmacy, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, China.
  • Sihui Huang
    Department of Pharmacy, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, China.
  • Fengxin Li
    Department of Pharmacy, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, China.
  • Zicheng Pang
    Department of Pharmacy, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, China.
  • Jian Luo
    School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
  • Danfeng Sun
    Department of Pharmacy, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, China.
  • Junsong Liu
    Department of Pharmacy, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, China.
  • Zhuoming Chen
    The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
  • Jian Qu
    Department of Mechanical Engineering, Texas A&M University, College Station, TX, USA.
  • Qiang Qu
    Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address: qiang@siat.ac.cn.