Advancing Mass Spectrometry-based Proteomic Analysis Strategies for the Investigation of Human Health and Disease

Download or read book Advancing Mass Spectrometry-based Proteomic Analysis Strategies for the Investigation of Human Health and Disease written by Justin Morgan McKetney and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation describes advances in mass spectrometry-based analysis of the human proteome and applies the most current technologies to investigations of age, neurodegeneration and stress. Although direct protein measurements in human tissues provide valuable insight into the development and progression of disease, the complex and dynamic nature of human proteomes provides several challenges. Chapter 1 details some of these hurdles along with the basic concepts of bottom-up proteomics in terms of sample preparation and instrument operation. Chapter 2 describes regional protein signatures for nine neuroanatomically distinct regions of the aged human brain. These region-specific proteins are then compared to proteins associated with Alzheimer's disease (AD). An efficient and scalable method for proteomic analysis of AD in cerebrospinal fluid is demonstrated in Chapter 3 using an age- and sex-matched sample cohort. In Chapter 4, a proteomic analysis is performed on saliva of soldiers before and after a simulated combat training exercise in order to quantify the proteomic effects of stress. To expand the method development toolkit for proteomics of human tissues and biofluids, a machine learning model is developed for predicting peptides' transmissive compensating voltage when using high field asymmetric waveform ion mobility spectrometry (FAIMS)(Chapter 5). Conclusions and future directions for these projects, including expanded analyses and continued technological development are discussed in Chapter 6. A chapter conveying aspects of this dissertation to a general public audience is included after the conclusion (Chapter 7).