Quantifying the Benefits of Imputation over QSAR Methods in Toxicology Data Modeling

• Published in: Journal of chemical information and modeling Vol. 64; no. 7; pp. 2624 - 2636
• Main Authors: Whitehead, Thomas M., Strickland, Joel, Conduit, Gareth J., Borrel, Alexandre, Mucs, Daniel, Baskerville-Abraham, Irene
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 08.04.2024
• Subjects: Biocompatibility; Data analysis; Data points; In vivo methods and tests; Machine learning; Machine Learning and Deep Learning; Modelling; Open data; Quantitative Structure-Activity Relationship; Regulatory agencies; Toxicity; Toxicology
• ISSN: 1549-9596; 1549-960X; 1549-960X
• DOI: 10.1021/acs.jcim.3c01695

Imputation machine learning (ML) surpasses traditional approaches in modeling toxicity data. The method was tested on an open-source data set comprising approximately 2500 ingredients with limited in vitro and in vivo data obtained from the OECD QSAR Toolbox. By leveraging the relationships between different toxicological end points, imputation extracts more valuable information from each data point compared to well-established single end point methods, such as ML-based Quantitative Structure Activity Relationship (QSAR) approaches, providing a final improvement of up to around 0.2 in the coefficient of determination. A significant aspect of this methodology is its resilience to the inclusion of extraneous chemical or experimental data. While additional data typically introduces a considerable level of noise and can hinder performance of single end point QSAR modeling, imputation models remain unaffected. This implies a reduction in the need for laborious manual preprocessing tasks such as feature selection, thereby making data preparation for ML analysis more efficient. This successful test, conducted on open-source data, validates the efficacy of imputation approaches in toxicity data analysis. This work opens the way for applying similar methods to other types of sparse toxicological data matrices, and so we discuss the development of regulatory authority guidelines to accept imputation models, a key aspect for the wider adoption of these methods.