Development of an AI model for DILI-level prediction using liver organoid brightfield images.

Journal: Communications biology
Published Date:

Abstract

AI image processing techniques hold promise for clinical applications by enabling analysis of complex status information from cells. Importantly, real-time brightfield imaging has advantages of informativeness, non-destructive nature, and low cost over fluorescence imaging. Currently, human liver organoids (HLOs) offer an alternative to animal models due to their excellent physiological recapitulation including basic functions and drug metabolism. Here we show a drug-induced liver injury (DILI) level prediction model using HLO brightfield images (DILITracer) considering that DILI is the major causes of drug withdrawals. Specifically, we utilize BEiT-V2 model, pretrained on 700,000 cell images, to enhance 3D feature extraction. A total of 30 compounds from FDA DILIrank are selected (classified into Most-, Less-, and No-DILI) to activate HLOs and corresponding brightfield images are collected at different time series and z-axis. Our computer vision model based on image-spatial-temporal coding layer excavates fully spatiotemporal information of continuously captured images, links HLO morphology with DILI severity, and final output DILI level of compounds. DILITracer achieves an overall accuracy of 82.34%. To our knowledge, this is the first model to output ternary classification of hepatotoxicity. Overall, DILITracer, using clinical data as an endpoint categorization label, offers a rapid and effective approach for screening hepatotoxic compounds.

Authors

  • Shiyi Tan
    Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
  • Yan Ding
    Department of Computer Science and Engineering, Changshu Institute of Technology, Changshu 215500, China.
  • Wei Wang
    State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
  • Jianhua Rao
    Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical University; Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.
  • Feng Cheng
    Phase I Clinical Trial Site, Nanjing Gaoxin Hospital, Nanjing, Jiangsu, China.
  • Qiuyin Zhang
    Jiangsu Institute for Sport and Health (JISH), Nanjing, China.
  • Tingting Xu
    Center for Information and Systems Engineering, Boston University, Boston, MA 02215 USA.
  • Tianmu Hu
    Jiangsu Institute for Sport and Health (JISH), Nanjing, China.
  • Qinyi Hu
    Jiangsu Institute for Sport and Health (JISH), Nanjing, China.
  • Ziliang Ye
    Jiangsu Institute for Sport and Health (JISH), Nanjing, China.
  • Xiaopeng Yan
    Technology on Electromechanical Dynamic Control Laboratory, School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China.
  • Xiaowei Wang
    Beijing Centers for Preventive Medical Research, Beijing 100013, China.
  • Mingyue Li
    Department of Obstetrics and Gynecology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, 224001 Jiangsu, China.
  • Peng Xie
    New Cornerstone Science Laboratory, SEU-ALLEN Joint Center, Institute for Brain and Intelligence, Southeast University, Nanjing, Jiangsu 210096, China.
  • Zaozao Chen
    State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, China; Institute of Biomaterials and Medical Devices, Southeast University, Suzhou, Jiangsu, 215163, China.
  • Geyu Liang
    Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China.
  • Yuepu Pu
    Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
  • Juan Zhang
    Guangdong R & D Center for Technological Economy RM. 802, Guangzhou, Guangdong, P.R. China.
  • Zhongze Gu
    State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, China; Institute of Biomaterials and Medical Devices, Southeast University, Suzhou, Jiangsu, 215163, China. Electronic address: gu@seu.edu.cn.