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Systems toxicology: real world applications and opportunities

Hartung, Thomas; FitzGerald, Rex E.; Jennings, Paul; Mirams, Gary R.; Peitsch, Manuel C.; Rostami-Hodjegan, Amin; Shah, Imran; Wilks, Martin F.; Sturla, Shana J.

Authors

Thomas Hartung

Rex E. FitzGerald

Paul Jennings

Manuel C. Peitsch

Amin Rostami-Hodjegan

Imran Shah

Martin F. Wilks

Shana J. Sturla



Abstract

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams ("big data"), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity.

Journal Article Type Article
Journal Chemical Research in Toxicology
Print ISSN 0893-228X
Electronic ISSN 1520-5010
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 30
Issue 4
APA6 Citation Hartung, T., FitzGerald, R. E., Jennings, P., Mirams, G. R., Peitsch, M. C., Rostami-Hodjegan, A., …Sturla, S. J. (in press). Systems toxicology: real world applications and opportunities. Chemical Research in Toxicology, 30(4), doi:10.1021/acs.chemrestox.7b00003
DOI https://doi.org/10.1021/acs.chemrestox.7b00003
Publisher URL http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.7b00003
Related Public URLs http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.7b00003
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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