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Systematic Reverse Engineering of Network Topologies: A Case Study of Resettable Bistable Cellular Responses

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dc.contributorVirginia Tech. Department of Biological Sciencesen
dc.contributorVirginia Bioinformatics Instituteen
dc.contributorVirginia Tech. Department of Computer Scienceen
dc.contributorVirginia Tech. Department of Genetics, Bioinformatics and Computational Biologyen
dc.contributorVirginia Tech. Department of Physicsen
dc.contributorVirginia Tech. Center for Modeling Immunity to Enteric Pathogens. Nutritional Immunology and Molecular Medicine Laboratoryen
dc.contributorUniversity of Arizona. Department of Molecular & Cellular Biologyen
dc.contributorBeijing Computational Science Research Centeren
dc.contributor.authorMondal, Debasishen
dc.contributor.authorDougherty, Edward T.en
dc.contributor.authorMukhopadhyay, Abhisheken
dc.contributor.authorCarbo, Adriaen
dc.contributor.authorYao, Guangen
dc.contributor.authorXing, Jianhuaen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentComputer Scienceen
dc.contributor.departmentPhysicsen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.contributor.editorCsikász-Nagy, Attilaen
dc.date.accessed2016-02-12en
dc.date.accessioned2016-02-16T08:03:30Zen
dc.date.available2016-02-16T08:03:30Zen
dc.date.issued2014-08-29en
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
dc.description.sponsorshipNational Science Foundationen
dc.description.sponsorshipDMS-0969417en
dc.description.sponsorshipNational Institutes of Healthen
dc.description.sponsorship5R01AT004308en
dc.description.sponsorshipHHSN272201000056en
dc.description.sponsorshipVirginia Tech. Open Access Subvention Funden
dc.format.extent12 p.en
dc.format.mimetypeapplication/pdfen
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
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0105833en
dc.identifier.issn1932-6203en
dc.identifier.issue8en
dc.identifier.urihttp://hdl.handle.net/10919/64827en
dc.identifier.urlhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0105833en
dc.identifier.volume9en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderMondal, Debasishen
dc.rights.holderDougherty, Edward T.en
dc.rights.holderMukhopadhyay, Abhisheken
dc.rights.holderCarbo, Adriaen
dc.rights.holderYao, Guangen
dc.rights.holderXing, Jianhuen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectNetwork motifsen
dc.subjectTopologyen
dc.subjectEngineering and technologyen
dc.subjectGene regulatory networksen
dc.subjectRandom walken
dc.subjectComputer softwareen
dc.subjectAlgorithmsen
dc.subjectGenetic networksen
dc.titleSystematic Reverse Engineering of Network Topologies: A Case Study of Resettable Bistable Cellular Responsesen
dc.title.serialPLOS Oneen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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