Computational and Theoretical Analysis of Influenza Virus Evolution and Immune System Dynamics

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dc.contributor.advisorDeem, Michael W.en_US
dc.creatorPan, Keyaoen_US
dc.date.accessioned2013-03-08T00:37:26Zen_US
dc.date.available2013-03-08T00:37:26Zen_US
dc.date.issued2011en_US
dc.description.abstractInfluenza causes annual global epidemics and severe morbidity and mortality. The influenza virus evolves to escape from immune system antibodies that bind to it. The immune system produces influenza virus specific antibodies by VDJ recombination and somatic hypermutation. In this dissertation, we analyze the mechanism of influenza virus evolution and immune system dynamics using theoretical modeling and computational simulation. The first half of this thesis discusses influenza virus evolution. The epidemiological data inspires a novel sequence-based antigenic distance measure for subtypes H1N1 and H3N2 virus, which are superior to the conventional measure using hemagglutination inhibition assay. Historical influenza sequences show that the selective pressure increases charge in immunodominant epitopes of the H3 hemagglutinin influenza protein. Statistical mechanics and high-performance computing technology predict fixation tendencies of the H3N2 influenza virus by free energy calculation. We introduce the notion of entropy from physics and informatics to identify the epitope regions of H1-subtype influenza A with application to vaccine efficacy. We also use entropy to quantify selection and diversity in viruses with application to the hemagglutinin of H3N2 influenza. Using the bacterial E. coli as a model, we show the evidence for recombination contributing to the evolution of extended spectrum β-lactamases (ES-BLs) in clinical isolates. A guinea pig experiment supports the discussion on influenza virus evolution. The second half of the thesis discusses immune system dynamics. We design a two-scale model to describe correlation in B cell VDJ usage of zebrafish. We also introduce a dynamical system to model original antigenic sin in influenza. This dissertation aims to help researchers understand the interaction between influenza virus and the immune system with a quantitative approach.en_US
dc.format.extent347 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS BIOENG. 2011 PANen_US
dc.identifier.citationPan, Keyao. "Computational and Theoretical Analysis of Influenza Virus Evolution and Immune System Dynamics." (2011) Diss., Rice University. <a href="https://hdl.handle.net/1911/70381">https://hdl.handle.net/1911/70381</a>.en_US
dc.identifier.digitalPanKen_US
dc.identifier.urihttps://hdl.handle.net/1911/70381en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectApplied sciencesen_US
dc.subjectBiological sciencesen_US
dc.subjectInfluenza virusen_US
dc.subjectVirus evolutionen_US
dc.subjectImmune systemen_US
dc.subjectEntropyen_US
dc.subjectBiomedical engineeringen_US
dc.subjectBioinformaticsen_US
dc.subjectBiophysicsen_US
dc.titleComputational and Theoretical Analysis of Influenza Virus Evolution and Immune System Dynamicsen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBioengineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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