8 results on '"LAUBENBACHER, R."'
Search Results
2. PlantSimLab - a modeling and simulation web tool for plant biologists.
- Author
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Ha S, Dimitrova E, Hoops S, Altarawy D, Ansariola M, Deb D, Glazebrook J, Hillmer R, Shahin H, Katagiri F, McDowell J, Megraw M, Setubal J, Tyler BM, and Laubenbacher R
- Subjects
- Internet, Systems Biology methods, User-Computer Interface, Computer Simulation, Models, Biological, Plants, Software
- Abstract
Background: At the molecular level, nonlinear networks of heterogeneous molecules control many biological processes, so that systems biology provides a valuable approach in this field, building on the integration of experimental biology with mathematical modeling. One of the biggest challenges to making this integration a reality is that many life scientists do not possess the mathematical expertise needed to build and manipulate mathematical models well enough to use them as tools for hypothesis generation. Available modeling software packages often assume some modeling expertise. There is a need for software tools that are easy to use and intuitive for experimentalists., Results: This paper introduces PlantSimLab, a web-based application developed to allow plant biologists to construct dynamic mathematical models of molecular networks, interrogate them in a manner similar to what is done in the laboratory, and use them as a tool for biological hypothesis generation. It is designed to be used by experimentalists, without direct assistance from mathematical modelers., Conclusions: Mathematical modeling techniques are a useful tool for analyzing complex biological systems, and there is a need for accessible, efficient analysis tools within the biological community. PlantSimLab enables users to build, validate, and use intuitive qualitative dynamic computer models, with a graphical user interface that does not require mathematical modeling expertise. It makes analysis of complex models accessible to a larger community, as it is platform-independent and does not require extensive mathematical expertise.
- Published
- 2019
- Full Text
- View/download PDF
3. A computational model of invasive aspergillosis in the lung and the role of iron.
- Author
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Oremland M, Michels KR, Bettina AM, Lawrence C, Mehrad B, and Laubenbacher R
- Subjects
- Animals, Female, Lung pathology, Mice, Models, Biological, Aspergillosis metabolism, Computer Simulation, Iron metabolism, Lung metabolism, Lung microbiology
- Abstract
Background: Invasive aspergillosis is a severe infection of immunocompromised hosts, caused by the inhalation of the spores of the ubiquitous environmental molds of the Aspergillus genus. The innate immune response in this infection entails a series of complex and inter-related interactions between multiple recruited and resident cell populations with each other and with the fungal cell; in particular, iron is critical for fungal growth., Results: A computational model of invasive aspergillosis is presented here; the model can be used as a rational hypothesis-generating tool to investigate host responses to this infection. Using a combination of laboratory data and published literature, an in silico model of a section of lung tissue was generated that includes an alveolar duct, adjacent capillaries, and surrounding lung parenchyma. The three-dimensional agent-based model integrates temporal events in fungal cells, epithelial cells, monocytes, and neutrophils after inhalation of spores with cellular dynamics at the tissue level, comprising part of the innate immune response. Iron levels in the blood and tissue play a key role in the fungus' ability to grow, and the model includes iron recruitment and consumption by the different types of cells included. Parameter sensitivity analysis suggests the model is robust with respect to unvalidated parameters, and thus is a viable tool for an in silico investigation of invasive aspergillosis., Conclusions: Using laboratory data from a mouse model of invasive aspergillosis in the context of transient neutropenia as validation, the model predicted qualitatively similar time course changes in fungal burden, monocyte and neutrophil populations, and tissue iron levels. This model lays the groundwork for a multi-scale dynamic mathematical model of the immune response to Aspergillus species.
- Published
- 2016
- Full Text
- View/download PDF
4. A virtual look at Epstein-Barr virus infection: biological interpretations.
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Duca KA, Shapiro M, Delgado-Eckert E, Hadinoto V, Jarrah AS, Laubenbacher R, Lee K, Luzuriaga K, Polys NF, and Thorley-Lawson DA
- Subjects
- Adolescent, Adult, B-Lymphocytes immunology, B-Lymphocytes pathology, B-Lymphocytes virology, Herpesvirus 4, Human isolation & purification, Herpesvirus 4, Human pathogenicity, Humans, Infectious Mononucleosis pathology, Palatine Tonsil immunology, Palatine Tonsil pathology, Software, Stochastic Processes, Time Factors, Virus Activation immunology, Virus Latency, Virus Physiological Phenomena, Computer Simulation, Herpesvirus 4, Human physiology, Infectious Mononucleosis immunology, Infectious Mononucleosis virology, Models, Immunological
- Abstract
The possibility of using computer simulation and mathematical modeling to gain insight into biological and other complex systems is receiving increased attention. However, it is as yet unclear to what extent these techniques will provide useful biological insights or even what the best approach is. Epstein-Barr virus (EBV) provides a good candidate to address these issues. It persistently infects most humans and is associated with several important diseases. In addition, a detailed biological model has been developed that provides an intricate understanding of EBV infection in the naturally infected human host and accounts for most of the virus' diverse and peculiar properties. We have developed an agent-based computer model/simulation (PathSim, Pathogen Simulation) of this biological model. The simulation is performed on a virtual grid that represents the anatomy of the tonsils of the nasopharyngeal cavity (Waldeyer ring) and the peripheral circulation--the sites of EBV infection and persistence. The simulation is presented via a user friendly visual interface and reproduces quantitative and qualitative aspects of acute and persistent EBV infection. The simulation also had predictive power in validation experiments involving certain aspects of viral infection dynamics. Moreover, it allows us to identify switch points in the infection process that direct the disease course towards the end points of persistence, clearance, or death. Lastly, we were able to identify parameter sets that reproduced aspects of EBV-associated diseases. These investigations indicate that such simulations, combined with laboratory and clinical studies and animal models, will provide a powerful approach to investigating and controlling EBV infection, including the design of targeted anti-viral therapies.
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- 2007
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- View/download PDF
5. Optimization and Control of Agent-Based Models in Biology: A Perspective
- Author
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An, G, Fitzpatrick, BG, Christley, S, Federico, P, Kanarek, A, Neilan, R Miller, Oremland, M, Salinas, R, Laubenbacher, R, and Lenhart, S
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Biological Sciences ,Mathematical Sciences ,Animals ,Computer Simulation ,Ecosystem ,Mathematical Concepts ,Models ,Biological ,Pest Control ,Biological ,Poaceae ,Rabbits ,Stochastic Processes ,Systems Analysis ,Systems Biology ,Systems Theory ,Agent-based modeling ,Optimal control ,Optimization ,Systems theory ,Bioinformatics ,Biological sciences ,Mathematical sciences - Abstract
Agent-based models (ABMs) have become an increasingly important mode of inquiry for the life sciences. They are particularly valuable for systems that are not understood well enough to build an equation-based model. These advantages, however, are counterbalanced by the difficulty of analyzing and using ABMs, due to the lack of the type of mathematical tools available for more traditional models, which leaves simulation as the primary approach. As models become large, simulation becomes challenging. This paper proposes a novel approach to two mathematical aspects of ABMs, optimization and control, and it presents a few first steps outlining how one might carry out this approach. Rather than viewing the ABM as a model, it is to be viewed as a surrogate for the actual system. For a given optimization or control problem (which may change over time), the surrogate system is modeled instead, using data from the ABM and a modeling framework for which ready-made mathematical tools exist, such as differential equations, or for which control strategies can explored more easily. Once the optimization problem is solved for the model of the surrogate, it is then lifted to the surrogate and tested. The final step is to lift the optimization solution from the surrogate system to the actual system. This program is illustrated with published work, using two relatively simple ABMs as a demonstration, Sugarscape and a consumer-resource ABM. Specific techniques discussed include dimension reduction and approximation of an ABM by difference equations as well systems of PDEs, related to certain specific control objectives. This demonstration illustrates the very challenging mathematical problems that need to be solved before this approach can be realistically applied to complex and large ABMs, current and future. The paper outlines a research program to address them.
- Published
- 2017
6. Cooperative development of logical modelling standards and tools with CoLoMoTo
- Author
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Naldi, A., Monteiro, P.T., Müssel, C., Kestler, H.A., Thieffry, D., Xenarios, I., Saez-Rodriguez, J., Helikar, T., Chaouiya, C., Albert, R., Barberis, M., Calzone, L., Chasapi, A., Cokelaer, T., Crespo, I., Dorier, J., Dräger, A., Hernandez, C., Hucka, M., de Jong, H., Keating, S.M., Klamt, S., Klarner, H., Laubenbacher, R., Le Novère, N., Niknejad, A., Rodriguez, N., Siebert, H., Stoll, G., Zañudo, J.G.T., Synthetic Systems Biology (SILS, FNWI), Systems Biology, Faculty of Science, and SILS Other Research (FNWI)
- Subjects
Societies, Scientific ,Statistics and Probability ,Computer science ,Cells ,Systems biology ,Control (management) ,Interoperability ,Context (language use) ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Software ,Animals ,Humans ,Computer Simulation ,Molecular Biology ,030304 developmental biology ,Reusability ,0303 health sciences ,business.industry ,Management science ,Systems Biology ,Models, Theoretical ,Computer Science Applications ,Computational Mathematics ,Identification (information) ,Computational Theory and Mathematics ,Cooperative development ,business ,Metabolic Networks and Pathways ,030217 neurology & neurosurgery ,Logical modelling - Abstract
The identification of large regulatory and signalling networks involved in the control of crucial cellular processes calls for proper modelling approaches. Indeed, models can help elucidate properties of these networks, understand their behaviour and provide (testable) predictions by performing in silico experiments. In this context, qualitative, logical frameworks have emerged as relevant approaches, as demonstrated by a growing number of published models, along with new methodologies and software tools. This productive activity now requires a concerted effort to ensure model reusability and interoperability between tools. Following an outline of the logical modelling framework, we present the most important achievements of the Consortium for Logical Models and Tools, along with future objectives. Our aim is to advertise this open community, which welcomes contributions from all researchers interested in logical modelling or in related mathematical and computational developments. Contact: contact@colomoto.org
- Published
- 2014
7. A virtual look at Epstein–Barr virus infection: Simulation mechanism
- Author
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Shapiro, M., Duca, K.A., Lee, K., Delgado-Eckert, E., Hawkins, J., Jarrah, A.S., Laubenbacher, R., Polys, N.F., Hadinoto, V., and Thorley-Lawson, D.A.
- Subjects
- *
EPSTEIN-Barr virus , *COMPUTER simulation , *T cells , *BLOOD , *LYMPH , *INFECTION - Abstract
Abstract: Epstein–Barr virus (EBV) is an important human pathogen that establishes a life-long persistent infection and for which no precise animal model exists. In this paper, we describe in detail an agent-based model and computer simulation of EBV infection. Agents representing EBV and sets of B and T lymphocytes move and interact on a three-dimensional grid approximating Waldeyer''s ring, together with abstract compartments for lymph and blood. The simulation allows us to explore the development and resolution of virtual infections in a manner not possible in actual human experiments. Specifically, we identify parameters capable of inducing clearance, persistent infection, or death. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
8. Cooperative development of logical modelling standards and tools with CoLoMoTo
- Author
-
Naldi, A., Monteiro, P.T., Müssel, C., Tools, Kestler, H.A., Thieffry, D., Xenarios, I., Saez-Rodriguez, J., Helikar, T., Chaouiya, C., Consortium for Logical Models, Tools, Albert, R., Barberis, M., Calzone, L., Chaouiya, C., Chasapi, A., Cokelaer, T., Crespo, I., Dorier, J., Dräger, A., Helikar, T., Hernandez, C., Hucka, M., de Jong, H., Keating, SM., Kestler, HA., Klamt, S., Klarner, H., Laubenbacher, R., Novère, NL., Monteiro, PT., Müssel, C., Naldi, A., Niknejad, A., Rodriguez, N., Saez-Rodriguez, J., Siebert, H., Stoll, G., Thieffry, D., Xenarios, I., and Zañudo, JG.
- Subjects
Animals ,Cells/metabolism ,Computer Simulation ,Humans ,Metabolic Networks and Pathways ,Models, Theoretical ,Societies, Scientific ,Software/standards ,Systems Biology/methods - Abstract
The identification of large regulatory and signalling networks involved in the control of crucial cellular processes calls for proper modelling approaches. Indeed, models can help elucidate properties of these networks, understand their behaviour and provide (testable) predictions by performing in silico experiments. In this context, qualitative, logical frameworks have emerged as relevant approaches, as demonstrated by a growing number of published models, along with new methodologies and software tools. This productive activity now requires a concerted effort to ensure model reusability and interoperability between tools. Following an outline of the logical modelling framework, we present the most important achievements of the Consortium for Logical Models and Tools, along with future objectives. Our aim is to advertise this open community, which welcomes contributions from all researchers interested in logical modelling or in related mathematical and computational developments.
- Published
- 2015
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