Machine Learning and Artificial Intelligence in Toxicological Sciences

Abstract

Machine learning and artificial intelligence approaches have revolutionized multiple disciplines, including toxicology. This review summarizes representative recent applications of machine learning and artificial intelligence approaches in different areas of toxicology, including physiologically based pharmacokinetic (PBPK) modeling, quantitative structure-activity relationship modeling for toxicity prediction, adverse outcome pathway analysis, high-throughput screening, toxicogenomics, big data, and toxicological databases. By leveraging machine learning and artificial intelligence approaches, now it is possible to develop PBPK models for hundreds of chemicals efficiently, to create in silico models to predict toxicity for a large number of chemicals with similar accuracies compared with in vivo animal experiments, and to analyze a large amount of different types of data (toxicogenomics, high-content image data, etc.) to generate new insights into toxicity mechanisms rapidly, which was impossible by manual approaches in the past. To continue advancing the field of toxicological sciences, several challenges should be considered: (1) not all machine learning models are equally useful for a particular type of toxicology data, and thus it is important to test different methods to determine the optimal approach; (2) current toxicity prediction is mainly on bioactivity classification (yes/no), so additional studies are needed to predict the intensity of effect or dose-response relationship; (3) as more data become available, it is crucial to perform rigorous data quality check and develop infrastructure to store, share, analyze, evaluate, and manage big data; and (4) it is important to convert machine learning models to user-friendly interfaces to facilitate their applications by both computational and bench scientists.

Keywords: artificial intelligence; computational toxicology; machine learning; physiologically based pharmacokinetic (PBPK) modeling; quantitative structure-activity relationship (QSAR).

Figure 1.

A timeline of the applications of machine learning (ML), artificial intelligence (AL), physiologically based pharmacokinetic (PBPK), and quantitative structure-activity relationship (QSAR) modeling approaches in the fields of pharmacology and toxicology. This figure was created based on Figure 3 in Zhu (2020), Figure 1 in Lin and Fisher (2020), and Figure 1 in Singh et al. (2020). Please refer to these references for the original references for the milestones listed in this figure.