Fedor Kazantsev1,2, Ilya Akberdin1,2,3, Sergey Lashin1,2, Natalia Ree1, Vladimir Timonov2, Alexander Ratushny4,5, Tamara Khlebodarova1, Vitaly Likhoshvai1,2. 1. * Institute of Cytology and Genetics SB RAS, Lavrentyev Avenue., 10, Novosibirsk 630090, Russia. 2. † Novosibirsk State University, Pirogova str. 2, Novosibirsk 630090, Russia. 3. ¶ Biology Department, San Diego State University, San Diego, CA 92182-4614, USA. 4. ‡ Center for Infectious Disease Research (Formerly Seattle, Biomedical Research Institute), Seattle, WA 98109, USA. 5. § Institute for Systems Biology, Seattle, WA 98109-5234, USA.
Abstract
MOTIVATION: Living systems have a complex hierarchical organization that can be viewed as a set of dynamically interacting subsystems. Thus, to simulate the internal nature and dynamics of the entire biological system, we should use the iterative way for a model reconstruction, which is a consistent composition and combination of its elementary subsystems. In accordance with this bottom-up approach, we have developed the MAthematical Models of bioMOlecular sysTems (MAMMOTh) tool that consists of the database containing manually curated MAMMOTh fitted to the experimental data and a software tool that provides their further integration. RESULTS: The MAMMOTh database entries are organized as building blocks in a way that the model parts can be used in different combinations to describe systems with higher organizational level (metabolic pathways and/or transcription regulatory networks). The tool supports export of a single model or their combinations in SBML or Mathematica standards. The database currently contains 110 mathematical sub-models for Escherichia coli elementary subsystems (enzymatic reactions and gene expression regulatory processes) that can be combined in at least 5100 complex/sophisticated models concerning more complex biological processes as de novo nucleotide biosynthesis, aerobic/anaerobic respiration and nitrate/nitrite utilization in E. coli. All models are functionally interconnected and sufficiently complement public model resources. AVAILABILITY: http://mammoth.biomodelsgroup.ru.
MOTIVATION: Living systems have a complex hierarchical organization that can be viewed as a set of dynamically interacting subsystems. Thus, to simulate the internal nature and dynamics of the entire biological system, we should use the iterative way for a model reconstruction, which is a consistent composition and combination of its elementary subsystems. In accordance with this bottom-up approach, we have developed the MAthematical Models of bioMOlecular sysTems (MAMMOTh) tool that consists of the database containing manually curated MAMMOTh fitted to the experimental data and a software tool that provides their further integration. RESULTS: The MAMMOTh database entries are organized as building blocks in a way that the model parts can be used in different combinations to describe systems with higher organizational level (metabolic pathways and/or transcription regulatory networks). The tool supports export of a single model or their combinations in SBML or Mathematica standards. The database currently contains 110 mathematical sub-models for Escherichia coli elementary subsystems (enzymatic reactions and gene expression regulatory processes) that can be combined in at least 5100 complex/sophisticated models concerning more complex biological processes as de novo nucleotide biosynthesis, aerobic/anaerobic respiration and nitrate/nitrite utilization in E. coli. All models are functionally interconnected and sufficiently complement public model resources. AVAILABILITY: http://mammoth.biomodelsgroup.ru.
Entities:
Keywords:
Mathematical models; de novo nucleotide synthesis; gene expression; gene network; generalized Hill functions; respiration