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Advances in Glycoproteomics and Glyco-biomarker Discovery Studies

Author : Francisca Owusu Gbormittah

Publisher :

Page : 176 pages

File Size : 10,64 MB

Release : 2014

Category : Biochemical markers

ISBN :

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Book Description

The development of analytical technologies to investigate the glycoproteome of clinical relevant samples has improved over the last 10 years. These new developments aim to improve the identification and quantification of disease-specific glyco-biomarkers, which are present at low amounts in biological matrices. Glyco-biomakers have the potential to significantly contribute to cancer discovery studies in specific areas such as; early diagnosis, prognosis, monitor cancer recurrence and improve the low survival rate of cancer. In this thesis, we focused on the development and application of novel liquid affinity chromatography fractionation platforms integrated with nano-LC-MS/MS to characterize and quantify the glycoproteome as well as selected glyco-biomarker candidates of cancer samples. In chapter 1, brief background information covering glycoproteomics and glyco-biomarker discovery studies is presented. Specifically, protein glycosylation process and how the field of 'omics', which includes glycoproteomics, have revolutionized clinical glyco-biomarkers discovery are discussed. Further, various disease models, current sample fractionation strategies and analytical methodologies involved in glyco-biomarker development pipeline and their significance as well as their short falls are described. Reviewing biomarker validation and current bio-infomatics tools utilized in glycoproteomics discovery studies concludes chapter 1. Chapter 2 details the development of a novel multi-dimensional affinity liquid chromatography fractionation approach that combines the depletion of the top 12 abundant proteins and multi-lectin fractionation of the human plasma. Evaluating and validating the reproducibility, specificity and overall recoveries of the platform demonstrated the suitability of the developed method in glyco-biomarker discovery studies of clinical samples. After establishing this robust platform, it was applied in chapter 3 to comprehensively study the global glycoproteome profile of clear cell renal cell carcinoma plasma (ccRCC) samples to identify and characterize potential biomarkers for early detection of the disease. During this study, protein abundance alterations as well as glycan shifts were investigated to understand the sub-proteome of ccRCC. Chapter 4 focuses on the structural characterization of a glycoprotein (clusterin) that was identified during the ccRCC biomarker discovery studies. Clusterin has been implicated in ccRCC cancer progression however; its structure and biological function(s) are not yet well defined. Therefore, to have more structural insights into clusterin, the protein was immuno-affinity purified from ccRCC plasma followed by tandem mass spectrometry to profile glycoforms, "N"-glycosylation sites and quantify glycan amounts. We discovered that the levels of bi-antennary digalactosylated disialylated (A2G2S2) and core fucosylated bi-antennary digalactosylated disialylated (FA2G2S2) glycans differed significantly in the plasma of patients before and after curative nephrectomy of localized ccRCC. In chapter 5, a multi-lectin affinity chromatography platform previously developed in our laboratory was optimized and applied to investigate glycoproteins and non-glycoproteins present in pancreatic cyst fluid samples. This study was aimed at identifying potential candidate markers for early detection of malignant cyst (pancreatic cancer precursor). Our data showed the identification of proteins with significant differential expression in mucinous cysts (malignant cyst) compared to non-mucinous cysts (benign) of which one protein (periostin) associated with cancer progression was confirmed by immunoblotting assay. In the final chapter (chapter 6), we summarize and conclude our findings in this work and provide our perspective on the potential of glycoproteins in glyco-biomarker discovery studies.



Integrative Proteomics

Author : Hon-Chiu Leung

Publisher : IntechOpen

Page : 454 pages

File Size : 34,66 MB

Release : 2012-02-24

Category : Science

ISBN : 9789535100706

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Book Description

Proteomics was thought to be a natural extension after the field of genomics has deposited significant amount of data. However, simply taking a straight verbatim approach to catalog all proteins in all tissues of different organisms is not viable. Researchers may need to focus on the perspectives of proteomics that are essential to the functional outcome of the cells. In Integrative Proteomics, expert researchers contribute both historical perspectives, new developments in sample preparation, gel-based and non-gel-based protein separation and identification using mass spectrometry. Substantial chapters are describing studies of the sub-proteomes such as phosphoproteome or glycoproteomes which are directly related to functional outcomes of the cells. Structural proteomics related to pharmaceutics development is also a perspective of the essence. Bioinformatics tools that can mine proteomics data and lead to pathway analyses become an integral part of proteomics. Integrative proteomics covers both look-backs and look-outs of proteomics. It is an ideal reference for students, new researchers, and experienced scientists who want to get an overview or insights into new development of the proteomics field.



Development of Glycomic and Glycoproteomic Methods for Biomarker Discovery

Author : Ting Song

Publisher :

Page : pages

File Size : 13,75 MB

Release : 2015

Category :

ISBN : 9781339542201

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Book Description

Glycosylation is an important post-translational modification of proteins present in the vast majority of human proteins. It has functions related to protein conformation, stabilization, membrane secretion, protein turnover control, proteinase hydrolysis protection, protein solubility, and cell recognition. For these reasons, they are potentially new sources of biomarkers and active targets of therapeutics and vaccines. The research described in chapter II is about the construction of a serum glycan library containing over 170 complete and partially structures. The library is then used to identify structures using nanoflow liquid chromatography and accurate mass spectrometry. With this approach, we identify the abundant glycans in serum and determine the structural variation of several individuals. A detailed map of oligosaccharides in serum will help guide the discovery and development of novel therapeutics, vaccines, and biomarkers. In chapter III, this method is applied to identify N-glycans from monoclonal antibodies. The glycosylation in recombinant monoclonal antibody (rMab) drugs is a major concern in the biopharmaceutical industry as it impacts the drugs' many attributes. Characterization is important but complicated by the intricate structures, micro-heterogeneity, and the limitations of current tools for structural analysis. These rMabs are mainly manufactured from Chinese hamster ovary (CHO) cells, mouse myeloma NS0 and mouse myeloma Sp2/0 cell lines, where non-human glycan contaminations are often observed. A detailed N-glycan library exclusively for rMabs was created, which can then be used for the rapid characterization of rMab glycosylation. Furthermore, a detailed structural library is developed for cancer cell surface glycosylation which aims to provide a rapid cell surface glycan identification method with detailed structures. Human colorectal epithelial adenocarcinoma cells (Caco-2) was used in chapter IV to demonstrate this method. Chapter V is focused on using glycomics and glycoproteomics approaches in biomarker discovery for osteonecrosis of the femoral head (ONFH). Both released glycan and glycopeptide analysis using nanoESI-Chip-TOF MS and site-specific glycan analysis using UPLC-Triple Quadrupole MS were performed on a clinical set of serum samples. A comprehensive glycosylation picture from glycan structures to corresponding proteins and glycosylation sites are drawn for ONFH.



Essentials of Glycobiology

Author : Ajit Varki

Publisher : CSHL Press

Page : 694 pages

File Size : 11,21 MB

Release : 1999

Category : Medical

ISBN : 9780879696818

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Book Description

Sugar chains (glycans) are often attached to proteins and lipids and have multiple roles in the organization and function of all organisms. "Essentials of Glycobiology" describes their biogenesis and function and offers a useful gateway to the understanding of glycans.



Glycosylation and Cancer

Author :

Publisher : Academic Press

Page : 418 pages

File Size : 28,16 MB

Release : 2015-02-26

Category : Science

ISBN : 0128016140

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Book Description

Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics. Provides information on cancer research Outstanding and original reviews Suitable for researchers and students



The Glycome

Author : Adeel Malik

Publisher : CRC Press

Page : 305 pages

File Size : 12,13 MB

Release : 2021-07-07

Category : Science

ISBN : 1000344320

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Book Description

This volume provides a comprehensive understanding of the enigmatic identity of the glycome, a complex but important area of research that has been largely ignored due to its complexity. The authors thoroughly deal with almost all aspects of the glycome, i.e., elucidation of the glycan identity enigma and its role in regulation of the cellular process, and in disease etiology. The book bridges the knowledge gap in understanding the glycome, from being a cell signature to its applications in disease etiology. In addition, it details many of the major insights regarding the possible role of the glycome in various diseases as a therapeutic marker. The book systematically covers the major aspects of the glycome, including the significance of substituting the diverse monosaccharide units to glycoproteins, the role of glycans in disease pathologies, and the challenges and advances in glycobiology. The authors stress the significance and huge encoding power of carbohydrates as well as provide helpful insights in framing the bigger picture. The Glycome: Understanding the Diversity and Complexity of Glycobiology details state-of-the-art developments and emerging challenges of glycome biology, which are going to be key areas of future research, not only in the glycobiology field but also in pharmaceutics.



Transforming Glycoscience

Author : National Research Council

Publisher : National Academies Press

Page : 171 pages

File Size : 15,63 MB

Release : 2012-10-23

Category : Science

ISBN : 0309260868

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Book Description

A new focus on glycoscience, a field that explores the structures and functions of sugars, promises great advances in areas as diverse as medicine, energy generation, and materials science, this report finds. Glycans-also known as carbohydrates, saccharides, or simply as sugars-play central roles in many biological processes and have properties useful in an array of applications. However, glycans have received little attention from the research community due to a lack of tools to probe their often complex structures and properties. Transforming Glycoscience: A Roadmap for the Future presents a roadmap for transforming glycoscience from a field dominated by specialists to a widely studied and integrated discipline, which could lead to a more complete understanding of glycans and help solve key challenges in diverse fields.



The Role of Glycosylation in Health and Disease

Author : Gordan Lauc

Publisher : Springer Nature

Page : 392 pages

File Size : 14,9 MB

Release : 2021-09-08

Category : Science

ISBN : 3030701158

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Book Description

Glycobiology is an emerging field of studying glycans (sugars) and glycoconjugates that are essentially involved in almost all biological processes, from fine-tuning glycoprotein function to protein-protein interactions, signaling, immune response, host-pathogen interactions, etc. However, due to structural complexity of glycans and analytical challenges this exciting field was lagging behind other areas of biology. With technological advancements growing number of glycans’ functions are being discovered and the study of glycans is becoming a cutting-edge discipline in basic and clinical research. Despite recent developments in glycobiology field, many aspects of glycosylation process still remain unknown, both in a healthy human organism and in pathological states. Human glycome is dynamic and changes with physiological triggers, immune challenges and disease. Atypical glycosylation is consequently a subject of disease biomarker research, and a target for therapeutic interventions. On the other hand, properties of glycosylated biotherapeutics are predominantly determined by their glycans. The Role of Glycosylation in Health and Disease provides a comprehensive overview of types and functions of glycans in a healthy human organism as well as their role in pathophysiology of different diseases and efficiency of glycosylated biotherapeutics. Written by the experts in the field, this book aims to bring glycobiology field closer to students, researchers in life sciences and professionals in biopharmaceutical industry.



Advancements of Mass Spectrometry in Biomedical Research

Author : Alisa G. Woods

Publisher : Springer

Page : 0 pages

File Size : 14,78 MB

Release : 2016-09-24

Category : Science

ISBN : 9783319378923

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Book Description

This volume explores the use of mass spectrometry for biomedical applications. Chapters focus on specific therapeutic areas such as oncology, infectious disease and psychiatry. Additional chapters focus on methodology as well as new technologies and instrumentation. This volume provides readers with a comprehensive and informative manual that will allow them to appreciate mass spectrometry and proteomic research but also to initiate and improve their own work. Thus the book acts as a technical guide but also a conceptual guide to the newest information in this exciting field. Mass spectrometry is the central tool used in proteomic research today and is rapidly becoming indispensable to the biomedical scientist. With the completion of the human genome project and the genomic revolution, the proteomic revolution has followed closely behind. Understanding the human proteome has become critical to basic and clinical biomedical research and holds the promise of providing comprehensive understanding of human physiological processes. In addition, proteomics and mass spectrometry are bringing unprecedented biomarker discovery and are helping to personalize medicine.



Antibody Glycosylation

Author : Marija Pezer

Publisher : Springer Nature

Page : 588 pages

File Size : 20,91 MB

Release : 2021-10-22

Category : Medical

ISBN : 3030769127

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Book Description

This book summarizes recent advances in antibody glycosylation research. Covering major topics relevant for immunoglobulin glycosylation - analytical methods, biosynthesis and regulation, modulation of effector functions - it provides new perspectives for research and development in the field of therapeutic antibodies, biomarkers, vaccinations, and immunotherapy. Glycans attached to both variable and constant regions of antibodies are known to affect the antibody conformation, stability, and effector functions. Although it focuses on immunoglobulin G (IgG), the most explored antibody in this context, and unravels the natural phenomena resulting from the mixture of IgG glycovariants present in the human body, the book also discusses other classes of human immunoglobulins, as well as immunoglobulins produced in other species and production systems. Further, it reviews the glycoanalytical methods applied to antibodies and addresses a range of less commonly explored topics, such as automatization and bioinformatics aspects of high-throughput antibody glycosylation analysis. Lastly, the book highlights application areas ranging from the ones already benefitting from antibody glycoengineering (such as monoclonal antibody production), to those still in the research stages (such as exploration of antibody glycosylation as a clinical or biological age biomarker), and the potential use of antibody glycosylation in the optimization of vaccine production and immunization protocols. Summarizing the current knowledge on the broad topic of antibody glycosylation and its therapeutic and biomarker potential, this book will appeal to a wide biomedical readership in academia and industry alike. Chapter 4 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.