Large screening programs such as the US Tox21 are releasing experimental in vitro results for many endpoints of relevance for human health. In (Q)SAR modelling, it is essential to clearly define the endpoint (OECD QSAR Validation Principle 1) and extract the most robust data points according to the definition. We have developed a comprehensive data curation procedure to interpret in vitro experimental data sets for (Q)SAR development, with modules for selecting actives according to quality of curve fittings, magnitude of activity and 'absolute' potency cut-offs, requiring non-cytotoxicity at activity concentration; extracting only very robust inactives; selecting only substances tested in high purity; and accounting for assay signal interference. A structure curation procedure with uniform representation of tautomeric classes of substances is also developed. The detailed method and a use case of modelling Tox21 data for an estrogen receptor α agonism assay with and without use of the method is presented.
Keywords: Data curation method; Estrogen receptor; QSAR; REACH; Tautomer structure representation; Tox21.
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.