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dc.contributor.authorPokrzywa, Revonda Mariaen_US
dc.date.accessioned2014-03-14T21:21:26Z
dc.date.available2014-03-14T21:21:26Z
dc.date.issued2009-10-08en_US
dc.identifier.otheretd-10142009-122741en_US
dc.identifier.urihttp://hdl.handle.net/10919/39938
dc.description.abstractOne of the primary goals of systems biology is to understand the complex underlying network of biochemical interactions which allow an organism to respond to environmental stimuli. Models of these biological interactions serve as a tool to both codify current understanding of these interactions as well as a starting point for scientific discovery. Due to the massive amount of information which is required for this modeling process, systems biology studies must often attempt to construct models which reflect the whole of the system while having access to only partial information. In some cases, the missing information will not have a confounding effect on the accuracy of the model. In other cases, there is the danger that this missing information will make the model useless. The focus of this thesis is to study the effect which missing information has on systems level studies within several different contexts. Specifically, we study two contexts : when the missing information takes the role of incomplete molecular interaction network knowledge and when it takes the role of unknown kinetic rate laws. These studies yield interesting results. We show that when metabolism is isolated from gene expression, the effects are not limited to those reactions under strong control by gene expression. Thus, incomplete understanding of molecular interaction networks may have unexpected effects on the resulting analysis. We also reveal that under the conditions of the current study, mass action was shown to be the superior substitute when the true rate equations for a biological system are unknown. In addition to studying the effect of missing information in the aforementioned contexts, we propose a method for limiting the parameter search space of biochemical systems. Even in ideal scenarios where both the molecular interaction network and the relevant kinetic rate equations are known, obtaining appropriate estimates for the unknown system parameters can be challenging. By employing a method which limits the parameter search space, we are able to acquire estimates for parameter values which are much closer to the true values than those which could be obtained otherwise.en_US
dc.publisherVirginia Techen_US
dc.relation.haspartPokrzywa_RM_D-2009.pdfen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectSystems Biologyen_US
dc.subjectMetabolomicsen_US
dc.subjectBiological Networksen_US
dc.titleSystems Biology in an Imperfect World: Modeling Biological Systems with Incomplete Informationen_US
dc.typeDissertationen_US
dc.contributor.departmentGenetics, Bioinformatics, and Computational Biologyen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineGenetics, Bioinformatics, and Computational Biologyen_US
dc.contributor.committeechairMendes, Pedro J. P.en_US
dc.contributor.committeememberHoeschele, Inaen_US
dc.contributor.committeememberMurali, T. M.en_US
dc.contributor.committeememberShulaev, Vladimiren_US
dc.contributor.committeememberLaubenbacher, Reinhard C.en_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-10142009-122741/en_US
dc.date.sdate2009-10-14en_US
dc.date.rdate2009-11-11
dc.date.adate2009-11-11en_US


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