Schweppe, Devin KMcGann, Christopher2025-10-022025-10-022025-10-022025McGann_washington_0250E_28755.pdfhttps://hdl.handle.net/1773/54034Thesis (Ph.D.)--University of Washington, 2025Mass spectrometry-based proteomics has emerged as a cornerstone technology for understanding biological systems, yet significant computational and methodological challenges still exist. This dissertation aims to improve three important areas of need in proteomics: intelligent data acquisition methodologies, peptide identification efficiency, and scalability of methods for characterizing DNA-protein interactions. Chapter 2 addresses the computational demands of modern proteomics by implementing fragment ion indexing in the widely-used Comet search algorithm. Chapter 3 introduces real-time spectral library search (RTLS), an intelligent data acquisition method that leverages whole-proteome spectral libraries to guide instrument decision-making during acquisition. Finally, Chapter 4 presents DNA O-MAP, a scalable method for characterizing locus-specific chromatin interactions that overcomes limitations of existing approaches.application/pdfen-USCC BYMass spectrometryProteomicsReal-time searchBiochemistryAnalytical chemistryCellular biologyGeneticsThesis