Title: Intersection of toxicogenomics and high throughput screening in the Tox21 program: an NIEHS perspective

Authors: B. Alex Merrick; Richard S. Paules; Raymond R. Tice

Addresses: Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA ' Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA ' Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

Abstract: Humans are exposed to thousands of chemicals with inadequate toxicological data. Advances in computational toxicology, robotic high throughput screening (HTS), and genome-wide expression have been integrated into the Tox21 program to better predict the toxicological effects of chemicals. Tox21 is a collaboration among US Government agencies initiated in 2008 that aims to shift chemical hazard assessment from traditional animal toxicology to target-specific, mechanism-based, biological observations using in vitro assays and lower organism models. HTS uses biocomputational methods for probing thousands of chemicals in in vitro assays for gene-pathway response patterns predictive of adverse human health outcomes. In 1999, NIEHS began exploring the application of toxicogenomics to toxicology and recent advances in NextGen sequencing should greatly enhance the biological content obtained from HTS platforms. We foresee an intersection of new technologies in toxicogenomics and HTS as an innovative development in Tox21. Tox21 goals, priorities, progress, and challenges will be reviewed.

Keywords: Tox21; high throughput screening; robotic HTS; toxicogenomics; computational toxicology; gene pathways; in vitro; NextGen sequencing; toxicological effects; chemicals; chemical hazard assessment; biocomputing.

DOI: 10.1504/IJBT.2015.074797

International Journal of Biotechnology, 2015 Vol.14 No.1, pp.7 - 27

Available online: 18 Feb 2016 *

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