Case study: the role of mechanistic network models in systems toxicology Peer-Reviewed Publications peerreviewedpublications Systems Toxicologysystemstoxicology Aug 9, 2013 20130809 Drug Discovery Today /content/dam/pmiscience/default-fallback-thumbnails/publication/GB-27-09-21--E4075_3840x2160.jpg Drug Discovery Today
      Peer-Reviewed Publications

      Case study: the role of mechanistic network models in systems toxicology

      Hoeng, J.; Talikka, M.; Martin, F.; Sewer, A.; Yang, X.; Iskandar, A.; Schlage, W. K.; Peitsch, M. C.
      Published
      Aug 9, 2013
      DOI
      10.1016/j.drudis.2013.07.023
      PMID
      23933191
      Link to publication
      Topic
      Summary

      Twenty first century systems toxicology approaches enable the discovery of biological pathways affected in response to active substances. Here, we briefly summarize current network approaches that facilitate the detailed mechanistic understanding of the impact of a given stimulus on a biological system. We also introduce our network-based method with two use cases and show how causal biological network models combined with computational methods provide quantitative mechanistic insights. Our approach provides a robust comparison of the transcriptional responses in different experimental systems and enables the identification of network-based biomarkers modulated in response to exposure. These advances can also be applied to pharmacology, where the understanding of disease mechanisms and adverse drug effects is imperative for the development of efficient and safe treatment options.

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