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dc.contributorVirginia Tech. Department of Biological Sciencesen_US
dc.contributorVirginia Bioinformatics Instituteen_US
dc.contributorVirginia Tech. Department of Computer Scienceen_US
dc.contributorVirginia Tech. Department of Genetics, Bioinformatics and Computational Biologyen_US
dc.contributorVirginia Tech. Department of Physicsen_US
dc.contributorVirginia Tech. Center for Modeling Immunity to Enteric Pathogens. Nutritional Immunology and Molecular Medicine Laboratoryen_US
dc.contributorUniversity of Arizona. Department of Molecular & Cellular Biologyen_US
dc.contributorBeijing Computational Science Research Centeren_US
dc.contributor.authorMondal, Debasishen_US
dc.contributor.authorDougherty, Edward T.en_US
dc.contributor.authorMukhopadhyay, Abhisheken_US
dc.contributor.authorCarbo, Adriaen_US
dc.contributor.authorYao, Guangen_US
dc.contributor.authorXing, Jianhuaen_US
dc.contributor.editorCsikász-Nagy, Attilaen_US
dc.identifier.citationMondal D, Dougherty E, Mukhopadhyay A, Carbo A, Yao G, et al. (2014) Systematic Reverse Engineering of Network Topologies: A Case Study of Resettable Bistable Cellular Responses. PLoS ONE 9(8): e105833. doi:10.1371/journal.pone.0105833en_US
dc.description.abstractA focused theme in systems biology is to uncover design principles of biological networks, that is, how specific network structures yield specific systems properties. For this purpose, we have previously developed a reverse engineering procedure to identify network topologies with high likelihood in generating desired systems properties. Our method searches the continuous parameter space of an assembly of network topologies, without enumerating individual network topologies separately as traditionally done in other reverse engineering procedures. Here we tested this CPSS (continuous parameter space search) method on a previously studied problem: the resettable bistability of an Rb-E2F gene network in regulating the quiescence-to-proliferation transition of mammalian cells. From a simplified Rb-E2F gene network, we identified network topologies responsible for generating resettable bistability. The CPSS-identified topologies are consistent with those reported in the previous study based on individual topology search (ITS), demonstrating the effectiveness of the CPSS approach. Since the CPSS and ITS searches are based on different mathematical formulations and different algorithms, the consistency of the results also helps cross-validate both approaches. A unique advantage of the CPSS approach lies in its applicability to biological networks with large numbers of nodes. To aid the application of the CPSS approach to the study of other biological systems, we have developed a computer package that is available in Information S1.en_US
dc.description.sponsorshipNational Science Foundationen_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.description.sponsorshipVirginia Tech. Open Access Subvention Funden_US
dc.format.extent12 p.en_US
dc.publisherPublic Library of Scienceen_US
dc.rightsAttribution 4.0 International*
dc.subjectNetwork motifsen_US
dc.subjectEngineering and technologyen_US
dc.subjectGene regulatory networksen_US
dc.subjectRandom walken_US
dc.subjectComputer softwareen_US
dc.subjectGenetic networksen_US
dc.titleSystematic Reverse Engineering of Network Topologies: A Case Study of Resettable Bistable Cellular Responsesen_US
dc.typeArticle - Refereeden_US
dc.rights.holderMondal, Debasishen_US
dc.rights.holderDougherty, Edward T.en_US
dc.rights.holderMukhopadhyay, Abhisheken_US
dc.rights.holderCarbo, Adriaen_US
dc.rights.holderYao, Guangen_US
dc.rights.holderXing, Jianhuen_US
dc.title.serialPLOS Oneen_US

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Attribution 4.0 International
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