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Author: Xiaofang Zhong (Ph.D.) Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
Stable-isotope labeling coupled with mass spectrometry (MS) has emerged as the central technology for proteome quantification. Chemical stable isotope labels can be categorized into two major classes, namely mass difference labels and isobaric labels. Based on the various labeling approaches, we firstly develop a strategy for discovery and verification of candidate biomarkers in cerebrospinal fluid of preclinical Alzheimer's disease (AD), an asymptomatic phase with neuropathological abnormalities but no cognitive impairment. To further improve quantification accuracy, we develop 5-plex mass defect-based N,N-dimethyl leucine (mdDiLeu) tags for quantitative proteomics as an MS1-centric quantification method. The limitations of current quantification methods used for biomarker verification include low specificity in complex backgrounds, limited analytical throughput, and wide dynamic range, we developed a hybrid offset-triggered multiplex absolute quantification (HOTMAQ) strategy for targeted proteomics. HOTMAQ combines cost-effective mass difference and isobaric tags to address these issues simultaneously. Given the controversial discovery of protein biomarkers in AD and no reliable protein biomarkers for early detection are available in mild cognitive impairment (MCI, a symptomatic predementia phase) or AD so far, it is pivotal to define new players to aid in accurate diagnosis of this devastating disease. Protein glycosylation is one of the most common and complex post-translational modifications (PTMs), playing a fundamental role in many key biological processes. we develop large-scale comparative N-glycoproteomics of cerebrospinal fluid to elucidate glycoprotein microheterogeneity and relate the subtle changes in glycan structural repertoire to disease progression of AD. Phosphorylation, another common PTM, has been revealed to regulate cell dedifferentiation in restenosis. Transforming growth factor beta (TGF-[beta]) and its signaling protein Smad3 play important roles in vascular restenosis, but very little is yet known about the downstream regulation in response to elevated TGF-[beta]/Smad3 in smooth muscle cell (SMC). We develop a highly multiplexed quantitative proteomics and phosphoproteomics approach to assess dynamic protein expression and phosphorylation changes in SMC. Taken together, this work not only improves the quantification strategies for discovery and targeted proteomics and global PTM analyses, but also presents a useful platform to discover biomarkers and explore the underlying molecular mechanism of several diseases.
Author: Xiaofang Zhong (Ph.D.) Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
Stable-isotope labeling coupled with mass spectrometry (MS) has emerged as the central technology for proteome quantification. Chemical stable isotope labels can be categorized into two major classes, namely mass difference labels and isobaric labels. Based on the various labeling approaches, we firstly develop a strategy for discovery and verification of candidate biomarkers in cerebrospinal fluid of preclinical Alzheimer's disease (AD), an asymptomatic phase with neuropathological abnormalities but no cognitive impairment. To further improve quantification accuracy, we develop 5-plex mass defect-based N,N-dimethyl leucine (mdDiLeu) tags for quantitative proteomics as an MS1-centric quantification method. The limitations of current quantification methods used for biomarker verification include low specificity in complex backgrounds, limited analytical throughput, and wide dynamic range, we developed a hybrid offset-triggered multiplex absolute quantification (HOTMAQ) strategy for targeted proteomics. HOTMAQ combines cost-effective mass difference and isobaric tags to address these issues simultaneously. Given the controversial discovery of protein biomarkers in AD and no reliable protein biomarkers for early detection are available in mild cognitive impairment (MCI, a symptomatic predementia phase) or AD so far, it is pivotal to define new players to aid in accurate diagnosis of this devastating disease. Protein glycosylation is one of the most common and complex post-translational modifications (PTMs), playing a fundamental role in many key biological processes. we develop large-scale comparative N-glycoproteomics of cerebrospinal fluid to elucidate glycoprotein microheterogeneity and relate the subtle changes in glycan structural repertoire to disease progression of AD. Phosphorylation, another common PTM, has been revealed to regulate cell dedifferentiation in restenosis. Transforming growth factor beta (TGF-[beta]) and its signaling protein Smad3 play important roles in vascular restenosis, but very little is yet known about the downstream regulation in response to elevated TGF-[beta]/Smad3 in smooth muscle cell (SMC). We develop a highly multiplexed quantitative proteomics and phosphoproteomics approach to assess dynamic protein expression and phosphorylation changes in SMC. Taken together, this work not only improves the quantification strategies for discovery and targeted proteomics and global PTM analyses, but also presents a useful platform to discover biomarkers and explore the underlying molecular mechanism of several diseases.
Author: W. Andy Tao Publisher: John Wiley & Sons ISBN: 1118969553 Category : Science Languages : en Pages : 448
Book Description
PROVIDES STRATEGIES AND CONCEPTS FOR UNDERSTANDING CHEMICAL PROTEOMICS, AND ANALYZING PROTEIN FUNCTIONS, MODIFICATIONS, AND INTERACTIONS—EMPHASIZING MASS SPECTROMETRY THROUGHOUT Covering mass spectrometry for chemical proteomics, this book helps readers understand analytical strategies behind protein functions, their modifications and interactions, and applications in drug discovery. It provides a basic overview and presents concepts in chemical proteomics through three angles: Strategies, Technical Advances, and Applications. Chapters cover those many technical advances and applications in drug discovery, from target identification to validation and potential treatments. The first section of Mass Spectrometry-Based Chemical Proteomics starts by reviewing basic methods and recent advances in mass spectrometry for proteomics, including shotgun proteomics, quantitative proteomics, and data analyses. The next section covers a variety of techniques and strategies coupling chemical probes to MS-based proteomics to provide functional insights into the proteome. In the last section, it focuses on using chemical strategies to study protein post-translational modifications and high-order structures. Summarizes chemical proteomics, up-to-date concepts, analysis, and target validation Covers fundamentals and strategies, including the profiling of enzyme activities and protein-drug interactions Explains technical advances in the field and describes on shotgun proteomics, quantitative proteomics, and corresponding methods of software and database usage for proteomics Includes a wide variety of applications in drug discovery, from kinase inhibitors and intracellular drug targets to the chemoproteomics analysis of natural products Addresses an important tool in small molecule drug discovery, appealing to both academia and the pharmaceutical industry Mass Spectrometry-Based Chemical Proteomics is an excellent source of information for readers in both academia and industry in a variety of fields, including pharmaceutical sciences, drug discovery, molecular biology, bioinformatics, and analytical sciences.
Author: Justin Morgan McKetney Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
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).
Author: Timothy D. Veenstra Publisher: John Wiley & Sons ISBN: 1118634411 Category : Science Languages : en Pages : 375
Book Description
Helps researchers in proteomics and oncology work together to understand, prevent, and cure cancer Proteomic data is increasingly important to understanding the origin and progression of cancer; however, most oncologic researchers who depend on proteomics for their studies do not collect the data themselves. As a result, there is a knowledge gap between scientists, who devise proteomic techniques and collect the data, and the oncologic researchers, who are expected to interpret and apply proteomic data. Bridging the gap between proteomics and oncology research, this book explains how proteomic technology can be used to address some of the most important questions in cancer research. Proteomic Applications in Cancer Detection and Discovery enables readers to understand how proteomic data is acquired and analyzed and how it is interpreted. Author Timothy Veenstra has filled the book with examples many based on his own firsthand research experience that clearly demonstrate the application of proteomic technology in oncology research, including the discovery of novel biomarkers for different types of cancers. The book begins with a brief introduction to systems biology, explaining why cancer is a systems biology disease. Next, it covers such topics as: Mass spectrometry in cancer research Application of proteomics to global phosphorylation analysis Search for biomarkers in biofluids Rise and fall of proteomic patterns for cancer diagnostics Emergence of protein arrays Role of proteomics in personalized medicine The final chapter is dedicated to the future prospects of proteomics in cancer research. By guiding readers through the latest proteomic technologies and their applications in cancer research, Proteomic Applications in Cancer Detection and Discovery enhances the ability of researchers in proteomics and researchers in oncology to collaborate in order to better understand cancer and develop strategies to prevent and treat it.
Author: Fengfei Ma (Ph.D.) Publisher: ISBN: Category : Languages : en Pages : 335
Book Description
Mass spectrometry (MS) has emerged as a central technology for biomedical research largely due to its capability to provide unprecedented insights into the compositions and structures of the proteome. Thousands of proteins and peptides can be characterized in a single experiment, shedding lights on the complex biological processes and enabling discovery of novel therapeutic targets. This dissertation is devoted to the development of novel liquid chromatography (LC)-MS based techniques to characterize proteins and decipher post-translational modifications (PTMs) qualitatively and quantitatively. Specifically, novel sample preparation strategy has been developed for improved sample recovery and unbiased extraction of different categories of proteins. State-of-the-art hybrid fragmentation methods have been established for large scale differentiation of 3- and 4- hydroxyproline isomers. Furthermore, an integrated pipeline for in-depth investigation of protein glycosylation has been developed and implemented. These innovative analytical methodologies have been successfully demonstrated and applied to comprehensive characterization of biological scaffolds and breast cancer cells, which provide valuable insights into multiple research areas including tissue engineering and cancer biology.
Author: Oscar Alzate Publisher: CRC Press ISBN: 1420076264 Category : Medical Languages : en Pages : 356
Book Description
In this, the post-genomic age, our knowledge of biological systems continues to expand and progress. As the research becomes more focused, so too does the data. Genomic research progresses to proteomics and brings us to a deeper understanding of the behavior and function of protein clusters. And now proteomics gives way to neuroproteomics as we beg
Author: Timothy D. Veenstra Publisher: John Wiley & Sons ISBN: 1118279247 Category : Science Languages : en Pages : 363
Book Description
An update to the popular guide to proteomics technology applications in biomedical research Building on the strength of the original edition, this book presents the state of the art in the field of proteomics and offers students and scientists new tools and techniques to advance their own research. Written by leading experts in the field, it provides readers with an understanding of new and emerging directions for proteomics research and applications. Proteomics for Biological Discovery begins by discussing the emergence of proteomics technologies and summarizing the potential insights to be gained from proteome-level research. The tools of proteomics, from conventional to novel techniques, are thoroughly covered, from underlying concepts to limitations and future directions. Later chapters provide an overview of the current developments in post-translational modification studies, structural proteomics, biochemical proteomics, applied proteomics, and bioinformatics relevant to proteomics. Chapters cover: Quantitative Proteomics for Differential Protein Expression Profiling; Protein Microarrays; Protein Biomarker Discovery; Biomarker Discovery using Mass Spectrometry Imaging; Protein-Protein Interactions; Mass Spectrometry Of Intact Protein Complexes; Crosslinking Applications in Structural Proteomics; Functional Proteomics; High Resolution Interrogation of Biological Systems via Mass Cytometry; Characterization of Drug-Protein Interactions by Chemoproteomics; Phosphorylation; Large-Scale Phosphoproteomics; and Probing Glycoforms of Individual Proteins Using Antibody-Lectin Sandwich Arrays. Presents a comprehensive and coherent review of the major issues in proteomic technology development, bioinformatics, strategic approaches, and applications Chapters offer a rigorous overview with summary of limitations, emerging approaches, questions, and realistic future industry and basic science applications Features new coverage of mass spectrometry for high throughput proteomic measurements, and novel quantitation strategies such as spectral counting and stable isotope labeling Discusses higher level integrative aspects, including technical challenges and applications for drug discovery Offers new chapters on biomarker discovery, global phosphorylation analysis, proteomic profiling using antibodies, and single cell mass spectrometry Proteomics for Biological Discovery is an excellent advanced resource for graduate students, postdoctoral fellows, and scientists across all the major fields of biomedical science.
Author: David W. Greening Publisher: Springer Nature ISBN: 1071629786 Category : Science Languages : en Pages : 591
Book Description
This third volume provides comprehensive protocols on pre-analytical, analytical, plasma, and serum proteomics. New and updated chapters are divided into nine sections, detailing blood processing and handling strategies, discovery- and targeted-based mass spectrometry, including workflows to aid in discovery and targeted data analysis, in addition to software and bioinformatics for the plasma proteome. This edition further integrates emerging areas in the development of technologies for plasma proteomics and assay platforms in biomarker discovery and translational proteomics, enrichment and detection strategies to understand the plasma proteome, and peptide, lipid and metabolite targeted assays. We also detail the emerging analysis of extracellular vesicles isolated from plasma. Written in the format of the highly successful Methods in Molecular Biology series, each of the 33 chapters includes an introduction to the topic, lists necessary materials and methods, includes hints and tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Serum/Plasma Proteomics: Methods and Protocols, Third Edition aims to be comprehensive guide for researchers.
Author: Haleem J. Issaq Publisher: Academic Press ISBN: 0128197889 Category : Science Languages : en Pages : 504
Book Description
Proteomic and Metabolomic Approaches to Biomarker Discovery, Second Edition covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution. The book describes methods and presents a standard operating procedure for sample selection, preparation and storage, as well as data analysis and modeling. This new standard effectively eliminates the differing methodologies used in studies and creates a unified approach. Readers will learn the advantages and disadvantages of the various techniques discussed, as well as potential difficulties inherent to all steps in the biomarker discovery process. This second edition has been fully updated and revised to address recent advances in MS and NMR instrumentation, high-field NMR, proteomics and metabolomics for biomarker validation, clinical assays of biomarkers and clinical MS and NMR, identifying microRNAs and autoantibodies as biomarkers, MRM-MS assay development, top-down MS, glycosylation-based serum biomarkers, cell surface proteins in biomarker discovery, lipodomics for cancer biomarker discovery, and strategies to design studies to identify predictive biomarkers in cancer research. Addresses the full range of proteomic and metabolomic methods and technologies used for biomarker discovery and validation Covers all steps involved in biomarker discovery, from study design to study execution Serves as a vital resource for biochemists, biologists, analytical chemists, bioanalytical chemists, clinical and medical technicians, researchers in pharmaceuticals and graduate students
Author: Xiaofang Zhong (Ph.D.)
Author: Xiaofang Zhong (Ph.D.)
Author: W. Andy Tao
Author: Justin Morgan McKetney
Author: Timothy D. Veenstra
Author: Fengfei Ma (Ph.D.)
Author: Oscar Alzate
Author: Timothy D. Veenstra
Author: David W. Greening
Author: Haleem J. Issaq
Author: Thiago Verano-Braga