Open Source Tools for Read-Across and Category Formation

Abstract

In this chapter, the requirements and challenges for computational tools to support category formation and read-across are summarised. A brief overview of the open source, open data and open standards approaches in chemoinformatics are presented. The opportunities offered by these kinds of “openness” are highlighted, with emphasis on open source applications specifically developed to address challenges posed by the REACH regulation. Structural similarity assessment is currently a common practice in forming categories and applying read-across, and in developing and validating (Q)SARs. The Toxmatch software provides several endpoint-specific similarity measures, with descriptors selected using a training set in combination with data mining methods. The Toxtree software implements several classification schemes for predicting various endpoints and relies primarily on chemical structure, metabolic pathways, physico-chemical properties and descriptors, calculated from chemical structure. In addition to making predictions for individual chemicals, Toxtree can be used to profile the toxicological hazard or mechanistic group of a set of chemicals. Ambit is anopen source software for chemoinformatics data management, which allows storage of a large number of chemical structures and toxicological data and provides a flexible means for exploration of structural and similarity spaces. Several examples of the application of read-across, initiated by an expert-defined search strategy and supported by Ambit search functionalities are described.