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Silicon Human: oxidative stress model for aging, Parkinson's disease and precision therapies

Kolodkin A.N., Sharma R.P., Colangelo A.M., Orlov Y.L., Jennen D., Briede J.J., Barberis M., Kumar V., Alberghina L., Westerhoff H.V.

Infrastructure for Systems Biology Europe (ISBE) Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, THE NETHERLANDS SysBio Centre of Systems Biology (ISBE), University of Milano-Bicocca, ITALY Laboratory of Neuroscience, University of Milano-Bicocca, ITALY The Digital Health Institute, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, THE NETHERLANDS; Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, THE NETHERLANDS Systems Biology, School of Biosciences and Medicine, University of Surrey, UNITED KINGDOM Environmental Engineering Laboratory, Departament d'Enginyeria Quimica, URV, SPAIN. IISPV, Hospital Universitari Sant Joan de Reus, Universitat Rovira I Virgili, Reus, SPAIN Molecular Cell Biology, VU University Amsterdam, THE NETHERLANDS; Manchester Centre for Integrative Systems Biology, UK

Systems Biology aims to understand biological emergence from the interactions of biomolecules, e.g. by integrating the knowledge about these interactions into a computer model and thereby reconstructing biological behavior in silico. In relation to the human, such an in silico replica of the whole body is the so-called Silicon Human. We can add medicine aspects to this model and, using the patient’s genome, transcriptome and proteome data, parameterize a Silicon Human for any patient individually (Silicon Patient), thereby propelling individualized medicine of any systems biological disease.

As a successful example of this systems biological approach, our mechanism-based experimentally validated model enabled us to predict in silico the influence of oxidative stress and various Parkinson’s disease conditions (e.g. mutations) on aging. We discuss how this Silicon Human may be used to develop personalized therapies of Parkinson’s disease [1,2].

References

1. Kolodkin, A.N., Prasad Sharma, R, Westerhoff, HV, Colangelo, AM, Ignatenko, A, Martorana, F., Jennen, D., Briede, J.J., Brady, N., Barberis, M., Mondeel, T.D.G.A., Papa, M., Kumar, V., Peters, B., Skupin, A., Alberghina, L., Balling, R., Westerhoff, H.V., ROS networks: designs, aging, Parkinson’s disease and precision therapies. npj Syst Biol Appl 6, 34 (2020). https://doi.org/10.1038/s41540-020-00150-w

2. Sharma, R.P., Kumar, V., Schuhmacher, M., Kolodkin, A.N., Westerhoff, H.V., Development and evaluation of a harmonized whole body physiologically based pharmacokinetic (PBPK) model for flutamide in rats and its extrapolation to humans, Environmental Research (2020), doi: https://doi.org/10.1016/j.envres.2019.108948

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