title: Using Petri nets for experimental design in a multi-organ elimination pathway.
abstract: Genistein is a soy metabolite with estrogenic activity that may result in (un)favorable effects on human health. Elucidation of the mechanisms through which food additives such as genistein exert their beneficiary effects is a major challenge for the food industry. A better understanding of the genistein elimination pathway could shed light on such mechanisms. We developed a Petri net model that represents this multi-organ elimination pathway and which assists in the design of future experiments. Using this model we show that metabolic profiles solely measured in venous blood are not sufficient to uniquely parameterize the model. Based on simulations we suggest two solutions that provide better results: parameterize the model using gut epithelium profiles or add additional biological constrains in the model.
authors.affiliation: Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands. Electronic address: p.reshetova@uva.nl.
authors.forename: Polina
authors.initials: P
authors.lastname: Reshetova
authors.affiliation: Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands. Electronic address: a.k.smilde@uva.nl.
authors.forename: Age K
authors.initials: AK
authors.lastname: Smilde
authors.affiliation: Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands. Electronic address: j.a.westerhuis@uva.nl.
authors.forename: Johan A
authors.initials: JA
authors.lastname: Westerhuis
authors.affiliation: Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands; Bioinformatics Laboratory, Academic Medical Center, University of Amsterdam, 1100 DE, Amsterdam, P.O. Box 22700, The Netherlands. Electronic address: a.h.vankampen@amc.uva.nl.
authors.forename: Antoine H C
authors.initials: AH
authors.lastname: van Kampen
mesh_terms: D000328:Adult; D005260:Female; D019833:Genistein / Q000493:pharmacokinetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008954:Models, Biological
chemical_list: D019833:Genistein
keywords: Elimination metabolic pathway; Experiment design; Genistein; Metabolic pathway parameterization; Petri nets