Complex systems biology approach to understanding coordination of JAK-STAT signaling
| Autor: | Radina P. Soebiyanto, Kenneth A. Loparo, Sree N. Sreenath, Cheng-Kui Qu, Kevin D. Bunting |
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| Rok vydání: | 2007 |
| Předmět: |
Statistics and Probability
Organizing principle Systems biology In silico Protein Tyrosine Phosphatase Non-Receptor Type 11 Suppressor of Cytokine Signaling Proteins Computational biology Biology Bioinformatics Models Biological Article General Biochemistry Genetics and Molecular Biology stat Interferon-gamma Animals Humans Complex systems biology Janus Kinases Systems Biology Applied Mathematics JAK-STAT signaling pathway General Medicine STAT Transcription Factors Modeling and Simulation Signal transduction Janus kinase Mathematics Signal Transduction |
| Zdroj: | Biosystems. 90:830-842 |
| ISSN: | 0303-2647 |
| Popis: | In this work, we search for coordination as an organizing principle in a complex signaling system using a multilevel hierarchical paradigm. The objective is to explain the underlying mechanism of Interferon (IFN γ ) induced JAK-STAT (specifically JAK1/JAK2-STAT1) pathway behavior. Starting with a mathematical model of the pathway from the literature, we modularize the system using biological knowledge via principles of biochemical cohesion, biological significance, and functionality. The modularized system is then used as a basis for in silico inhibition, knockdown/deletion and perturbation experiments to discover a coordination mechanism. Our analysis shows that a module representing the SOCS1 complex can be identified as the coordinator. Analysis of the coordinator can then be used for the selection of biological experiments for the discovery of ‘soft’ molecular drug targets, that could lead to the development of improved therapeutics. The coordinator identified is also being investigated to determine its relationship to pathological conditions. |
| Databáze: | OpenAIRE |
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