BiliQML: a supervised machine-learning model to quantify biliary forms from digitized whole slide liver histopathological images.

Journal: American journal of physiology. Gastrointestinal and liver physiology
PMID:

Abstract

The progress of research focused on cholangiocytes and the biliary tree during development and following injury is hindered by limited available quantitative methodologies. Current techniques include two-dimensional standard histological cell-counting approaches, which are rapidly performed, error prone, and lack architectural context or three-dimensional analysis of the biliary tree in opacified livers, which introduce technical issues along with minimal quantitation. The present study aims to fill these quantitative gaps with a supervised machine-learning model (BiliQML) able to quantify biliary forms in the liver of anti-keratin 19 antibody-stained whole slide images. Training utilized 5,019 researcher-labeled biliary forms, which following feature selection, and algorithm optimization, generated an score of 0.87. Application of BiliQML on seven separate cholangiopathy models [genetic (-CRE;, CRE;, and CRE;), surgical (bile duct ligation), toxicological (3,5-diethoxycarbonyl-1,4-dihydrocollidine), and therapeutic ( with ileal bile acid transporter inhibition)] allowed for a means to validate the capabilities and utility of this platform. The results from BiliQML quantification revealed biological and pathological differences across these seven diverse models, indicating a highly sensitive, robust, and scalable methodology for the quantification of distinct biliary forms. BiliQML is the first comprehensive machine-learning platform for biliary form analysis, adding much-needed morphologic context to standard immunofluorescence-based histology, and provides clinical and basic science researchers with a novel tool for the characterization of cholangiopathies. BiliQML is the first comprehensive machine-learning platform for biliary form analysis in whole slide histopathological images. This platform provides clinical and basic science researchers with a novel tool for the improved quantification and characterization of biliary tract disorders.

Authors

  • Dominick J Hellen
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States.
  • Meredith E Fay
    The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA, USA.
  • David H Lee
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States.
  • Caroline Klindt-Morgan
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States.
  • Ashley Bennett
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States.
  • Kimberly J Pachura
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States.
  • Arash Grakoui
    Emory National Primate Research Center, Division of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States.
  • Stacey S Huppert
    Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
  • Paul A Dawson
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States.
  • Wilbur A Lam
    The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu.
  • Saul J Karpen
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States.