title: The silicon trypanosome: a test case of iterative model extension in systems biology.
abstract: The African trypanosome, Trypanosoma brucei, is a unicellular parasite causing African Trypanosomiasis (sleeping sickness in humans and nagana in animals). Due to some of its unique properties, it has emerged as a popular model organism in systems biology. A predictive quantitative model of glycolysis in the bloodstream form of the parasite has been constructed and updated several times. The Silicon Trypanosome is a project that brings together modellers and experimentalists to improve and extend this core model with new pathways and additional levels of regulation. These new extensions and analyses use computational methods that explicitly take different levels of uncertainty into account. During this project, numerous tools and techniques have been developed for this purpose, which can now be used for a wide range of different studies in systems biology.
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Achcar
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Abeer
authors.initials: A
authors.lastname: Fadda
authors.affiliation: Department of Pediatrics, Centre for Liver Digestive and Metabolic Diseases, and Systems Biology Centre for Energy Metabolism and Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Molecular Cell Physiology, Faculty of Earth and Life Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jurgen R
authors.initials: JR
authors.lastname: Haanstra
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, and Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Systems and Synthetic Biology Group, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Kerkhoven
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, and Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Biochemie-Zentrum der Universität Heidelberg, Heidelberg, Germany.
authors.forename: Alejandro E
authors.initials: AE
authors.lastname: Leroux
authors.affiliation: The Department of Statistical Science and The Centre for Computational Statistics and Machine Learning University College London, London, United Kingdom.
authors.forename: Theodore
authors.initials: T
authors.lastname: Papamarkou
authors.affiliation: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojas
authors.affiliation: Department of Pediatrics, Centre for Liver Digestive and Metabolic Diseases, and Systems Biology Centre for Energy Metabolism and Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bakker
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, and Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Barrett
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Clayton
authors.affiliation: The Department of Statistical Science and The Centre for Computational Statistics and Machine Learning University College London, London, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Girolami
authors.affiliation: Biochemie-Zentrum der Universität Heidelberg, Heidelberg, Germany.
authors.forename: R Luise
authors.initials: RL
authors.lastname: Krauth-Siegel
authors.affiliation: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Matthews
authors.affiliation: Manchester Institute of Biotechnology, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. Electronic address: rainer.breitling@manchester.ac.uk.
authors.forename: Rainer
authors.initials: R
authors.lastname: Breitling
mesh_terms: D000818:Animals; D006019:Glycolysis; D006801:Humans; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*; D014353:Trypanosomiasis, African / Q000469:parasitology*
chemical_list: D015800:Protozoan Proteins
keywords: Differential equations; Dynamic modelling; Metabolomics; Systems biology; Transcriptomics; Trypanosoma brucei; Uncertainty