Editorial pubs.acs.org/crt
Systems Toxicology: A Special Issue his issue of Chemical Research in Toxicology is dedicated to aspects of the new field of Systems Toxicology. Systems Toxicology is the study of complex networks of molecular responses to active substances with the aim of developing quantitative mechanistic and dynamic models that may be predictive of toxic outcomes on the basis of in vitro data. It relies on applying chemistry-based bioanalysis tools to understand how xenobiotic substances perturb biological systems. Major advancements in systems-wide measurements, data-integration strategies, and functional network models together with the pressing need to characterize better the toxicity of a growing list of commercial and environmental chemicals and their mixtures has fueled the recent growth of this area. Chemical Research in Toxicology encourages the publication of Systems Toxicology papers that best illustrate these tenets. In this issue, a wide range of topics can be found, but the collection is by no means a comprehensive survey of Systems Toxicology; rather, it represents examples of current research and ideas that are driving the science forward. The review “Systems Toxicology: From Basic Research to Risk Assessment” provides a broad overview of the motivators and strategies in the area. It describes bioanalytical and computational analysis approaches, and it relates how the resulting knowledge of adverse-outcome pathways could be used to improve the practice of risk assessment. Although this review primarily addresses the most prominent large-scale molecular measurements, namely, transcriptomics, proteomics, and metabolomics, three additional review articles in this issue address innovative and complementary topics concerning systems-oriented approaches for studying DNA adducts, RNA modifications, and quantitative imaging of stress-response pathways. The primary research articles in this issue examine a variety of chemicals and their influence on biomolecule structure and function. These studies examine, for example, inhaled toxicants, bioactive food components, electrophilic chemicals that modify human serum albumin, environmental chemicals with thyroiddisrupting activity, chemicals that influence the development of the central nervous system, and chemicals that affect hepatotoxicity or adverse drug reactions. In many cases, these studies involve the development of new strategies and tools for bioanalysis, including a high-throughput assay and a new enrichment strategy for protein adductomics. Additional articles in this issue offer multifaceted, cell-based test systems with common themes involving attention to cell types that avoid genetic modifications associated with cancer cell lines, concentration and time dependence of molecular responses, and comprehensive data curation, analysis, and integration strategies that enable the use of gene ontologies and mechanistic network models to describe toxicity pathways. Finally, this issue contains an example of a Chemical Profile, a Chemical Research in Toxicology manuscript type that is a short report of systems-oriented data that characterizes the influence of specific chemicals on global cellular processes.
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© 2014 American Chemical Society
A catalyst for this special issue was the Systems Toxicology 2013 meeting, held in Ascona, Switzerland, which was generously sponsored in part by ACS Publications and Chemical Research in Toxicology. A main theme of the meeting was bridging basic research to human risk assessment, but the presentations and discussions also addressed closely related systems and advances in ecotoxicology. Many of the authors of the articles in this issue were participants at the meeting, and more details can be found on the meeting’s Web site (www. SysTox2013.ch). The results and ideas presented in this issue are early steps toward evaluating how state-of-the-art systems biology approaches can be used to elucidate toxic modes of action. We hope that they will resonate with the readership and encourage our readers to contribute in new ways to decoding toxicity mechanisms on the basis of chemical research.
Shana J. Sturla, Guest Editor
Department of Health Science and Technology, ETH Zürich, Zürich 8092, Switzerland
Paul Hollenberg, Feature Editor
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Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, United States
AUTHOR INFORMATION
Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.
Special Issue: Systems Toxicology Published: March 17, 2014 311
dx.doi.org/10.1021/tx500024u | Chem. Res. Toxicol. 2014, 27, 311−311
