Open (Quantitative) Structure–activity/property Relationship App (OPERA) updates

The Open (Quantitative) Structure–activity/property Relationship App (OPERA) is a free and open-source/open-data suite of QSAR models developed to support a range of research and regulatory purposes. In addition to physicochemical and environmental fate properties, OPERA offers a number of models predicting ADME endpoints that are important to PBPK modeling and in vitro to in vivo extrapolation (IVIVE) studies. All OPERA models were built using curated data sets split into training and test sets and molecular descriptors calculated based on standardized QSAR-ready chemical structures. Modeling adhered to the five principles for QSAR model development adopted by OECD. These principles support development of scientifically valid, high-accuracy models with minimal complexity that support mechanistic interpretation, when possible. For consistency and transparency, OPERA provides a tool for standardizing chemical structures, an estimate of prediction accuracy, an assessment of applicability domain, and incorporation of experimental values when available. Technical and performance details are described in OECD-compliant QSAR Model Reporting Format reports.

Existing OPERA models are updated regularly when new experimental data are available. Version 2.9, released in September 2022, updated a number of physicochemical properties and ADME parameters covering different classes of chemicals including PFAS. OPERA predictions are available through the EPA CompTox Chemicals Dashboard and NICEATM’s Integrated Chemical Environment. The OPERA application can also be downloaded from the NIEHS GitHub repository as a command-line or graphical user interface for Windows and Linux operating systems. To enable broader access, in September 2022 OPERA became available as an extension to OECD’s QSAR Toolbox, a resource provided by OECD and the European Chemicals Agency to support animal-free chemical hazard assessment.