Predictive Modeling of Tox21 Data

Abstract

As an alternative to traditional animal toxicology studies, the toxicology for the twenty-first century (Tox21) program initiated a large-scale, systematic screening of chemicals against target-specific, mechanism-oriented in vitro assays aiming to predict chemical toxicity based on these in vitro assay data. The Tox21 library of ~10,000 environmental chemicals and drugs, representing a wide range of structural diversity, has been tested in triplicate against a battery of cell-based assays in a quantitative high-throughput screening (qHTS) format generating over 85 million data points that have been made publicly available. This chapter describes efforts to build in vivo toxicity prediction models based on in vitro activity profiles of compounds. Limitations of the current data and strategies to select an optimal set of assays for improved model performance are discussed. To encourage public participation in developing new methods and models for toxicity prediction, a “crowd-sourcing” challenge was organized based on the Tox21 assay data with successful outcomes.