Development of a QSAR model to predict hepatic steatosis using freely available machine learning tools

• Published in: Food and chemical toxicology 2020-08, Vol.142, p.111494, Article 111494
• Main Authors: Cotterill, J., Price, N., Rorije, E., Peijnenburg, A.
• Format: Article
• Language: English
• Subjects: Algorithms; Environmental Pollutants - chemistry; Environmental Pollutants - toxicity; Humans; Machine Learning; Non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - chemically induced; Non-alcoholic Fatty Liver Disease - metabolism; QSAR model; Quantitative Structure-Activity Relationship; Steatosis
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2020.111494

There are various types of hepatic steatosis of which non-alcoholic fatty liver disease, which may be caused by exposure to chemicals and environmental pollutants is the most prevalent, representing a potential major health risk. QSAR modelling has the potential to provide a rapid and cost-effective method to identify compounds which may trigger steatosis. Although models exist to predict key molecular initiating events of steatosis such as nuclear receptor binding, we are aware of no models to predict the apical effect steatosis. In this study, we describe the development of a QSAR model to predict steatosis using freely available machine learning tools. It was built using a dataset of 207 pharmaceuticals and pesticides which were identified as steatotic or non-steatotic from existing data from in vivo human and animal studies. The best performing model developed using the linear discriminant analysis module in TANAGRA, based on four chemical descriptors, had an accuracy of 70%, a sensitivity of 66% and a specificity of 74%. The expansion of the steatosis dataset to other chemical types, to enable the development of further models, would be of benefit in the identification of compounds with a range of mechanisms of action contributing to steatosis. •QSAR model to predict steatosis developed using in vivo data.•Complements models for specific Nuclear Receptors associated with steatosis.•Model developed using freely available learning tools.