MUFINS: multi-formalism interaction network simulator
| Autor: | Catherine Linley, Hans V. Westerhoff, Ahmad A. Mannan, Andrzej M. Kierzek, Lara Ward, Wataru Mori, Nick Plant, Axel von Kamp, Nilgun Sahin, Hiroshi Matsuno, Nicholas Stoy, Jacek Sroka, Johnjoe McFadden, Vytautas Leoncikas, David J. M. Lewis, Huihai Wu, Steffen Klamt, Graham R. Stewart, Marek Grabowski, Albert Gevorgyan |
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| Přispěvatelé: | Synthetic Systems Biology (SILS, FNWI), Molecular Cell Physiology, AIMMS |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Theoretical computer science Computer science Systems biology Metabolic network General Biochemistry Genetics and Molecular Biology QH301 03 medical and health sciences 0302 clinical medicine Software Interaction network Manchester Institute of Biotechnology Drug Discovery Journal Article QA Simulation business.industry Applied Mathematics Linear model Petri net ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology Technology Feature Rotation formalisms in three dimensions QR Computer Science Applications 030104 developmental biology Modeling and Simulation User interface business 030217 neurology & neurosurgery |
| Zdroj: | Wu, H, von Kamp, A, Leoncikas, V, Mori, W, Sahin, N, Gevorgyan, A, Linley, C, Grabowski, M, Mannan, A A, Stoy, N, Stewart, G R, Ward, L T, Lewis, D J M, Sroka, J, Matsuno, H, Klamt, S, Westerhoff, H V, McFadden, J, Plant, N J & Kierzek, A M 2016, ' MUFINS: multi-formalism interaction network simulator ', npj Systems Biology and Applications, vol. 2, 16032 . https://doi.org/10.1038/npjsba.2016.32 Wu, H, von Kamp, A, Leoncikas, V, Mori, W, Sahin, N, Gevorgyan, A, Linley, C, Grabowski, M, Mannan, A A, Stoy, N, Stewart, G R, Ward, L T, Lewis, D J M, Sroka, J, Matsuno, H, Klamt, S, Westerhoff, H V, McFadden, J, Plant, N J & Kierzek, A M 2016, ' MUFINS: multi-formalism interaction network simulator ', NPJ systems biology and applications, vol. 2, 16032 . https://doi.org/10.10-38/npjsba.2016.32 Npj Systems Biology and Applications, 2:16032. Nature Publishing Group NPJ systems biology and applications, 2:16032. Nature Publishing Group NPJ Systems Biology and Applications npj Systems Biology and Applications |
| ISSN: | 2056-7189 |
| DOI: | 10.1038/npjsba.2016.32 |
| Popis: | Systems Biology has established numerous approaches for mechanistic modeling of molecular networks in the cell and a legacy of models. The current frontier is the integration of models expressed in different formalisms to address the multi-scale biological system organization challenge. We present MUFINS (MUlti-Formalism Interaction Network Simulator) software, implementing a unique set of approaches for multi-formalism simulation of interaction networks. We extend the constraint-based modeling (CBM) framework by incorporation of linear inhibition constraints, enabling for the first time linear modeling of networks simultaneously describing gene regulation, signaling and whole-cell metabolism at steady state. We present a use case where a logical hypergraph model of a regulatory network is expressed by linear constraints and integrated with a Genome-Scale Metabolic Network (GSMN) of mouse macrophage. We experimentally validate predictions, demonstrating application of our software in an iterative cycle of hypothesis generation, validation and model refinement. MUFINS incorporates an extended version of our Quasi-Steady State Petri Net approach to integrate dynamic models with CBM, which we demonstrate through a dynamic model of cortisol signaling integrated with the human Recon2 GSMN and a model of nutrient dynamics in physiological compartments. Finally, we implement a number of methods for deriving metabolic states from ~omics data, including our new variant of the iMAT congruency approach. We compare our approach with iMAT through the analysis of 262 individual tumor transcriptomes, recovering features of metabolic reprogramming in cancer. The software provides graphics user interface with network visualization, which facilitates use by researchers who are not experienced in coding and mathematical modeling environments. |
| Databáze: | OpenAIRE |
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