Case study: the role of mechanistic network models in systems toxicology.
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.
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
Julia
J
Hoeng
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
Marja
M
Talikka
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
Florian
F
Martin
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
Alain
A
Sewer
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
Xiang
X
Yang
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
Anita
A
Iskandar
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
Walter K
WK
Schlage
Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: manuel.peitsch@pmi.com.
Manuel C
MC
Peitsch
D015415:Biomarkers / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008954:Models, Biological; D049490:Systems Biology / Q000379:methods*; D014116:Toxicology / Q000379:methods
D015415:Biomarkers