Using 2D Structural Alerts to Define Chemical Categories for Molecular Initiating Events.


Molecular initiating events (MIEs) are important concepts for in silico predictions. They can be used to link chemical characteristics to biological activity through an adverse outcome pathway (AOP). In this work, we capture chemical characteristics in 2D structural alerts, which are then used as models to predict MIEs. An automated procedure has been used to identify these alerts, and the chemical categories they define have been used to provide quantitative predictions for the activity of molecules that contain them. This has been done across a diverse group of 39 important pharmacological human targets using open source data. The alerts for each target combine into a model for that target, and these models are joined into a tool for MIE prediction with high average model performance (sensitivity = 82%, specificity = 93%, overall quality = 93%, Matthews correlation coefficient = 0.57). The result is substantially improved from our previous study (Allen, T. E. H., Goodman, J. M., Gutsell, S., and Russell, P. J. 2016. A history of the molecular initiating event. Chem. Res. Toxicol. 29, 2060-2070) for which the mean sensitivity for each target was only 58%. This tool provides the first step in an AOP-based risk assessment, linking chemical structure to toxicity endpoint.Unileve

Similar works

Full text

oaioai:www.repository.cam.ac.uk:1810/279614Last time updated on 1/12/2019

This paper was published in Apollo.

Having an issue?

Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.