Novel Algorithms and Software for the Acquisition and Analysis of Mass Spectrometry-based Proteomics Data

Download or read book Novel Algorithms and Software for the Acquisition and Analysis of Mass Spectrometry-based Proteomics Data written by Austin Vincent Carr and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteomics technologies enable the large-scale, high-throughput study of proteoforms inbiological systems. The foremost approach, bottom-up proteomics, can identify and quantify thousands of proteins. However, the analysis of proteoforms is hindered by the required enzymatic digestion. Top-down proteomics does not require enzymatic digestion, enabling proteoform-level analysis. The technical challenge of analyzing proteoforms has thwarted the proliferation of top-down approaches, particularly compared to the ubiquity of bottom-up proteomics. Recent advances in sample preparation have enabled the intact mass measurements of classes of proteoforms traditionally considered challenging for top-down proteomics. Consequently, key barriers to broader applicability remaining in top-down proteomics are data acquisition and data processing. An additional challenge to proteomics in general is data interpretation. Lists of thousands of quantified proteins and/or proteoforms per experiment are not interpretable without software solutions capable of converting the raw output of proteomics experiments into biologically meaningful and actionable insight. This dissertation describes software-based solutions designed to improve the acquisition, processing, and interpretation of proteomics data. Chapter 1 provides an overview of mass spectrometry and the three key challenges addressed by methods in this thesis. Chapter 2 address challenges in data acquisition by introducing automated database searching of a data independent acquisition method for top-down proteomics using a hybrid database search strategy. Chapter 3 describes a new deconvolution method for low-resolution mass spectrometry data processing, taking top-down proteomics beyond high-resolution instruments. Chapter 4 also describes improvements in top-down proteomics data processing, applying astronomical averaging with outlier rejection algorithms to mass spectrometry data. In Chapter 5, a description of the application MetaNetwork, a computer program designed to facilitate systems biology insights for proteomics data is given.