Development of a Top-Down Proteomics Platform for Characterizing Myelin Basic Protein Proteoforms

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dc.contributor.advisorYu, Yonghaoen
dc.contributor.committeeMemberMonson, Nancy L.en
dc.contributor.committeeMemberGrishin, Nick V.en
dc.contributor.committeeMemberPatrie, Steven M.en
dc.creatorPlymire, Daniel Alvanen
dc.creator.orcid0000-0001-5134-4848
dc.date.accessioned2020-01-02T18:19:52Z
dc.date.available2020-01-02T18:19:52Z
dc.date.created2017-12
dc.date.issued2017-07-31
dc.date.submittedDecember 2017
dc.date.updated2020-01-02T18:19:52Z
dc.descriptionPages x-xv are misnumbered as pages xi-xvi.en
dc.description.abstractA top-down proteomic analysis platform for the analysis of myelin basic protein was designed and applied to murine central nervous system tissue. The compatibility of superficially porous (SP) resin for label-free intact protein analysis of myelin basic protein with on-line capillary liquid chromatography mass spectrometry was demonstrated and was able to resolve splice variants and individual proteoforms of myelin basic protein. Data independent acquisition using nozzle skimmer dissociation yielded fragment ions that were used with novel informatics procedures to identify proteoforms of MBP. The informatics procedures including continuous elution proteoform scoring, a three-tier search methodology, and a ranking system for identification validation yielded 323 unique proteoforms from a single splice variant of MBP from a single LC run. A novel site of acylation and two novel splice variants derived from a novel transcriptional start site were also identified.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1134688745
dc.identifier.urihttps://hdl.handle.net/2152.5/7730
dc.language.isoenen
dc.subjectChromatography, Reverse-Phaseen
dc.subjectMass Spectrometryen
dc.subjectMyelin Basic Proteinen
dc.subjectProteomicsen
dc.titleDevelopment of a Top-Down Proteomics Platform for Characterizing Myelin Basic Protein Proteoformsen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineMolecular Biophysicsen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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