Mass Spectrometry Based Metabolomics Platform Development And Application To Neurodegenerative Disease

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Mass Spectrometry-Based Metabolomics: Platform Development and Application to Neurodegenerative Disease

Author : He Huang
Publisher :
ISBN 13 :
Total Pages : 236 pages
Book Rating : 4.:/5 (114 download)

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Book Synopsis Mass Spectrometry-Based Metabolomics: Platform Development and Application to Neurodegenerative Disease by : He Huang

Download or read book Mass Spectrometry-Based Metabolomics: Platform Development and Application to Neurodegenerative Disease written by He Huang and published by . This book was released on 2017 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolites are small molecules that participate in critical cellular processes that include energy production, macromolecules biosynthesis, and signaling pathways. Metabolic dysregulation is associated with changes in homeostasis and disease pathology. Measuring metabolite changes at the sites of tissue dysfunction can reveal new mechanisms that could serve as therapeutic targets and aid in the biomarker discovery. In this dissertation, we develop an untargeted metabolomic platform based on tandem mass spectrometry (TripleTOF 5600+, SCIEX). The platform consists of: hydrophilic interaction chromatography - mass spectrometry (HILIC-MS) to separate and detect polar metabolites and direct infusion-based based shotgun lipidomics. The platform allows global metabolic profiling in approximately thirty minutes. Three neurodegenerative diseases, including multiple sclerosis, normal pressure hydrocephalus (NPH), and Chiari malformation type I (CMI) are examined by this platform. First, dimethyl fumarate (DMF) treated oligodendrocytes are examined to provide mechanistic insight into potential neuroprotective pathways that may be upregulated by this treatment. Results indicate DMF alters levels of intermediates in the citric acid cycle to induce antioxidant responses in oligodendrocytes. Secondly, cerebrospinal fluid (CSF) samples were collected longitudinally from NPH patients following moderate exercise in order to elucidate pathological mechanisms of this disease as well as categorize potential biomarkers of treatment response. The results indicate that moderate exercise induces changes in CSF metabolites in NPH patient. These metabolic alterations are associated with the levels of vascular endothelial growth factor (VEGF) and patient clinical responses to shunting. Finally, both CSF and serum metabolites of CMI are investigated. Neurotransmitter and neuropeptide alterations were found to be associated with CMI. These results suggest that alterations in neurotransmission might underlie symptoms such as pain in this disorder. In this dissertation, unique metabolic alterations are detected by the untargeted metabolomic platform and suggest novel pathways that might be further examined as therapeutic interventions to alleviate neurological symptoms and promote CNS regeneration.

Metabolomics in Health and Disease Biology

Author :
Publisher : Elsevier
ISBN 13 : 0443137269
Total Pages : 248 pages
Book Rating : 4.4/5 (431 download)

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Book Synopsis Metabolomics in Health and Disease Biology by :

Download or read book Metabolomics in Health and Disease Biology written by and published by Elsevier. This book was released on 2024-02-26 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolomics in Health and Disease Biology, Volume 104 covers this rapidly emerging field that aims for metabolic phenotyping and understanding the blueprint of metabolic pathways under various health and disease conditions by comprehensive analysis of metabolites. Chapters in this new release include Metabolomics approaches: Biomarkers to Disease mechanisms, Metabolomics in sleep disorders, Metabolomics in predicting the hallmark of Cancer Metabolism, Spectroscopic based rapid metabolic fingerprinting approaches for Cancer diagnosis, Lipidomics in assessing the health of osteoarthritis, Metabolomics Applications in Type 2 Diabetes mellitus, Metabolomics of Diabetic retinopathy, Metabolomics in Neurodegenerative disorders- Parkinson's disease, and Metabolomic of Neurodegenerative disorder: Alzheimer's Disease. - Presents crucial reviews from selected experts in the field of metabolomics, with cross-disciplinary contributions - Provides the latest insights into our understanding of diseases using metabolomics-based approaches - Includes graphical material for metabolomics application that provide useful information for ease of reading of audience

Development and Broad Application of a Mass Spectrometry Based Metabolomics Platform

Author : Jay Steven Kirkwood
Publisher :
ISBN 13 :
Total Pages : 207 pages
Book Rating : 4.:/5 (859 download)

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Book Synopsis Development and Broad Application of a Mass Spectrometry Based Metabolomics Platform by : Jay Steven Kirkwood

Download or read book Development and Broad Application of a Mass Spectrometry Based Metabolomics Platform written by Jay Steven Kirkwood and published by . This book was released on 2013 with total page 207 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolomics is a comprehensive analysis of small molecules, or metabolites, in a system. Metabolomics is a hypothesis-generating experiment and offers an unbiased analysis of cell metabolism that can aid in the understanding of fundamental biological processes. Metabolomics is widely and broadly applicable in the biological sciences and has been used to study gene function, elucidate mechanisms of drug action, develop novel therapeutics, and to better understand disease states. This dissertation presents studies aimed at developing and determining the suitability of a mass spectrometry based untargeted metabolomics platform. Four chapters of original research are presented in this dissertation. The first chapter describes the development of a liquid chromatography-quadrupole-time-of-flight mass spectrometry metabolomics platform and details the various steps involved in a typical metabolomics experiment including metabolite extraction/sample preparation, metabolite separation and data collection, data processing and statistical analysis, and metabolite identification. The second chapter applies the metabolomics platform to uncover the metabolic consequences of vitamin C deficiency in zebrafish, which, like humans cannot synthesize vitamin C and must acquire it through diet for survival. In addition to uncovering several metabolic changes in vitamin C deficient zebrafish previously reported in genetic animal models of vitamin C deficiency, we found evidence for increased purine nucleotide cycle activity. These results demonstrate the suitability of zebrafish for the study of dietary vitamin C deficiency and highlight the roles of vitamin C in energy metabolism. The third chapter describes a metabolomics driven effort to characterize the antiobesity effects and mechanisms of xanthohumol, a prenylated flavonoid found in hops. Based on a metabolomics analysis of plasma from fatty rats treated with xanthohumol, we measure the bioenergetic effects of xanthohumol on cells in culture and find that it is a general mitochondrial uncoupler. We hypothesize that it is through this mechanism that xanthohumol exerts its anti-obesity effects in vivo. The fourth chapter investigates the temporal metabolome changes that occur during adipocyte differentiation. Using time course metabolomics, we uncovered increases in several uncharacterized di- and tripeptides, presumably products of protein degradation. We then treated differentiating adipocytes with 18O labeled water and found incorporation of 18O into the peptides, confirming them as products of peptide or protein hydrolysis. In addition, H218O metabolomics revealed enhanced flux through the CDP-choline cycle and activation of glutaminolysis during adipocyte differentiation, highlighting the utility of 18O labeled water metabolomics to uncover alterations in metabolic pathways undetectable with a typical metabolomics experiment.

Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines

Author : Aihua Zhang
Publisher : John Wiley & Sons
ISBN 13 : 3527835741
Total Pages : 292 pages
Book Rating : 4.5/5 (278 download)

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Book Synopsis Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines by : Aihua Zhang

Download or read book Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines written by Aihua Zhang and published by John Wiley & Sons. This book was released on 2021-08-20 with total page 292 pages. Available in PDF, EPUB and Kindle. Book excerpt: Highlights the importance and benefit of mass spectrometry-based metabolomics for identifying biomarkers that accurately screen for potential biomarkers of diseases Mass spectrometry-based metabolomics offer new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has been applied to discovering and identifying the perturbed pathways. Currently, mass spectrometry-based metabolomics has become an important tool in clinical research and the diagnosis of human disease. Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines comprehensively presents the current state, challenges, and applications of high-throughput mass spectrometry-based metabolomics such as metabolites analysis, biomarker discovery, technical challenges, discovery of natural product, mechanism interpretation of action, discovery of active ingredients, clinical application and precision medicine, and enhancing their biomedical value in a real world of biomedicine, shedding light on the potential for spectrometry-based metabolomics. It highlights the value of mass spectrometry-based metabolomics and metabolism to address the complexity of herbal medicines in systems pharmacology, especially, to link phytochemical analysis with the assessment of pharmacological effect and therapeutic potential. Each chapter has been laid out with introduction, method, up-to-date literature, identification of biomarker, and applications Covers the current state, challenges, and applications of high-throughput mass spectrometry-based metabolomics in the discovery of biomarker, active ingredients, natural product, etc. Constitutes a unique and indispensable practical guide for any phytochemistry or related laboratory, and provides hands-on description of new techniques Provides a guide for new practitioners of pharmacologists, pharmacological scholars, drug developers, botanist, researchers of traditional medicines. Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines provides a landmark of mass spectrometry-based metabolomics research and a beneficial guideline to graduate students and researchers in academia, industry, and technology transfer organizations in all biomedical science fields.

Development and Application of Mass Spectrometry-based Metabolomics for Characterization of Type 2 Diabetes and Diabetic Cardiomyopathy

Download Development and Application of Mass Spectrometry-based Metabolomics for Characterization of Type 2 Diabetes and Diabetic Cardiomyopathy PDF Online Free

Author : Benjamin Wancewicz
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (145 download)

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Book Synopsis Development and Application of Mass Spectrometry-based Metabolomics for Characterization of Type 2 Diabetes and Diabetic Cardiomyopathy by : Benjamin Wancewicz

Download or read book Development and Application of Mass Spectrometry-based Metabolomics for Characterization of Type 2 Diabetes and Diabetic Cardiomyopathy written by Benjamin Wancewicz and published by . This book was released on 2024 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Diabetes mellitus (DM) is a global epidemic, currently affecting more than 537 million adults worldwide. Type 2 diabetes mellitus (T2D) is the predominant form of DM, making up over 90% of the cases. Individuals with diabetes are at an increased risk of cardiovascular complications, which is termed diabetic cardiomyopathy (DCM), and these complications are their primary source of mortality. The early stages of DCM are marked by shifts in glucose metabolism, as well as lipid metabolism. Mass-spectrometry metabolomics has been used to study these shifts and is a natural tool to survey the large changes that are present. However, challenges remain in accessing the plasma and cardiac metabolome in a comprehensive manner. The research described herein involves the development and application of metabolomics approaches, namely in sample preparation and characterization by mass spectrometry, to investigate metabolic shifts in T2D. Chapter 1 provides an introduction to diabetes, metabolomics, and the mouse models used to study diabetes. In Chapter 2, a highly reproducible and high-throughput method for plasma metabolomics was developed. Using a single-phase extraction method, flow injection, and the Fourier-transform ion cyclotron resonance mass spectrometer (FTICR MS), a broad range of metabolites and lipids were observed. In Chapter 3, this metabolomics platform was used to analyze plasma samples from patients with diabetes undergoing either metformin or diet and lifestyle intervention. Fatty acid metabolism was observed to differ between the two diabetic groups with the levels in the metformin group being significantly different than diet and lifestyle group. In Chapter 4, a comprehensive analysis of the human heart was undertaken with six extraction methods and four metabolomics platforms to determine the best approach for investigating cardiac metabolism. In Chapter 5, the heart of a high fat diet mouse model of DCM was investigated. Alterations in the lipidome were observed with a particular shift in acyl chain composition in ceramides, triglycerides, and cardiolipins.

Development and Application of Mass Spectrometry-based Metabolomics Methods for Disease Biomarker Identification

Author : Lily Victoria Tong
Publisher :
ISBN 13 :
Total Pages : 299 pages
Book Rating : 4.:/5 (367 download)

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Book Synopsis Development and Application of Mass Spectrometry-based Metabolomics Methods for Disease Biomarker Identification by : Lily Victoria Tong

Download or read book Development and Application of Mass Spectrometry-based Metabolomics Methods for Disease Biomarker Identification written by Lily Victoria Tong and published by . This book was released on 2008 with total page 299 pages. Available in PDF, EPUB and Kindle. Book excerpt: (cont.) We sought to investigate whether the addition of metabolomic information would result in increased accuracy of mortality prediction. One hundred twenty patient samples were obtained from a national dialysis study (equally representing death and survival within 90 days of starting dialysis) and analyzed according to our protocol. Two feature selection algorithms were applied to identify significant metabolites distinguishing death and survival, and the corresponding models resulted in improved receiver-operating characteristic (ROC) curve areas of 0.85 and 0.93. This result constitutes a significant improvement from existing clinical models, which at best result in ROC curve areas of 0.80. Based on this work, we hypothesize that our observed differential fatty acid concentrations are indicative of impaired fatty acid oxidation, leading to insulin resistance in ESRD patients (regardless of Type II diabetes status) and eventually, patient mortality.

Advancing Mass Spectrometry-based Metabolomics and Proteomics

Author : Ling Hao
Publisher :
ISBN 13 :
Total Pages : 439 pages
Book Rating : 4.:/5 (11 download)

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Book Synopsis Advancing Mass Spectrometry-based Metabolomics and Proteomics by : Ling Hao

Download or read book Advancing Mass Spectrometry-based Metabolomics and Proteomics written by Ling Hao and published by . This book was released on 2017 with total page 439 pages. Available in PDF, EPUB and Kindle. Book excerpt: Quantitative analysis of endogenous biomolecules offers a wealth of clues to understand cell biology and disease mechanisms. Mass spectrometry (MS) has become a foremost technology for the study of biomolecules and their dynamic alterations involved in disease processes. This dissertation is devoted to the development of novel and improved MS-based metabolomic and proteomic methodologies and the application to human disease studies. Specifically, both label-free and stable isotope labeling strategies have been developed for the analysis of metabolites, peptides, and proteins in various biological systems. Label-free methods provide straightforward measurements of biomolecules and are combined with advanced bioinformatics tools for biomarker discovery. Stable isotope labeling, particularly custom DiLeu, iDiLeu, and mdDiLeu tags, offers high-throughput and accurate quantification of biomolecules. Novel online software platform has also been developed for automated omics data analysis. The advancements of analytical methodologies in this work have been mainly achieved on standard flow liquid chromatography (LC)-MS, nanoflow LC-MS, and capillary electrophoresis (CE)-MS platforms. Comprehensive metabolomic and proteomic studies have been successfully applied to disease biomarker discovery for human Preclinical Alzheimer's Disease and Lower Urinary Tract Symptoms in human and mouse models.

Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines

Author : Aihua Zhang
Publisher : John Wiley & Sons
ISBN 13 : 352734991X
Total Pages : 292 pages
Book Rating : 4.5/5 (273 download)

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Book Synopsis Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines by : Aihua Zhang

Download or read book Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines written by Aihua Zhang and published by John Wiley & Sons. This book was released on 2021-09-07 with total page 292 pages. Available in PDF, EPUB and Kindle. Book excerpt: Highlights the importance and benefit of mass spectrometry-based metabolomics for identifying biomarkers that accurately screen for potential biomarkers of diseases Mass spectrometry-based metabolomics offer new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has been applied to discovering and identifying the perturbed pathways. Currently, mass spectrometry-based metabolomics has become an important tool in clinical research and the diagnosis of human disease. Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines comprehensively presents the current state, challenges, and applications of high-throughput mass spectrometry-based metabolomics such as metabolites analysis, biomarker discovery, technical challenges, discovery of natural product, mechanism interpretation of action, discovery of active ingredients, clinical application and precision medicine, and enhancing their biomedical value in a real world of biomedicine, shedding light on the potential for spectrometry-based metabolomics. It highlights the value of mass spectrometry-based metabolomics and metabolism to address the complexity of herbal medicines in systems pharmacology, especially, to link phytochemical analysis with the assessment of pharmacological effect and therapeutic potential. Each chapter has been laid out with introduction, method, up-to-date literature, identification of biomarker, and applications Covers the current state, challenges, and applications of high-throughput mass spectrometry-based metabolomics in the discovery of biomarker, active ingredients, natural product, etc. Constitutes a unique and indispensable practical guide for any phytochemistry or related laboratory, and provides hands-on description of new techniques Provides a guide for new practitioners of pharmacologists, pharmacological scholars, drug developers, botanist, researchers of traditional medicines. Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines provides a landmark of mass spectrometry-based metabolomics research and a beneficial guideline to graduate students and researchers in academia, industry, and technology transfer organizations in all biomedical science fields.

Mass Spectrometry-Based Metabolomics

Author : Sastia Prama Putri
Publisher : CRC Press
ISBN 13 : 1482223767
Total Pages : 298 pages
Book Rating : 4.4/5 (822 download)

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Book Synopsis Mass Spectrometry-Based Metabolomics by : Sastia Prama Putri

Download or read book Mass Spectrometry-Based Metabolomics written by Sastia Prama Putri and published by CRC Press. This book was released on 2014-11-19 with total page 298 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mass Spectrometry-Based Metabolomics: A Practical Guide is a simple, step-by-step reference for profiling metabolites in a target organism. It discusses optimization of sample preparation for urine, serum, blood, tissue, food, and plant and animal cell samples. Encompassing three different technical fields—biology, analytical chemistry, and informatics— mass spectrometry-based metabolomics can be challenging for biologists without special training in quantitative mass spectrometry. This book is designed to overcome this limitation by providing researchers with the knowledge they need to use metabolomics technology in their respective disciplines. The book summarizes all steps in metabolomics research, from experimental design to sample preparation, analytical procedures, and data analysis. Case studies are presented for easy understanding of the metabolomics workflow and its practical applications in different research fields. The book includes an in-house library and built-in software so that those new to the field can begin to analyze real data samples. In addition to being an excellent introductory text, the book also contains the latest advancements in this emerging field and can thus be a useful reference for metabolomics specialists.

Mass Spectrometry-based Metabolomics and Lipidomics Empowered by Software Enables Hardware and Applications

Author : Benton J. Anderson
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (143 download)

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Book Synopsis Mass Spectrometry-based Metabolomics and Lipidomics Empowered by Software Enables Hardware and Applications by : Benton J. Anderson

Download or read book Mass Spectrometry-based Metabolomics and Lipidomics Empowered by Software Enables Hardware and Applications written by Benton J. Anderson and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work describes advancements in mass spectrometry metabolomics and lipidomics. Chapter 1 introduces mass spectrometry omics for biological discovery and puts the field in the context of the broader omics field, and gives a framework for how this author thinks about mass spectrometry as a collaborative entity for describing and enabling biological insights across fields and groups of people. Chapter 2 describes the Nile rat plasma lipidomics and polar metabolomics in support of developing the animal as a complementary model of human diabetes. Chapter 3 describes advancements in lipidomics data processing in LipiDex 2, focusing on quality control in Degreaser QC module and MSn tree-based fragmentation method support via library generation and integrated support in spectral matching and peak annotation modules. Chapter 4 details the development of a real-time mass spectrometry-based urine metabolomics platform. Chapter 5 concludes the work with final thoughts on the role of the mass spectrometry analyst, future directions for lipidomics and future software upgrades to the LipiDex 2 feature set.

A Mass Spectrometry Imaging-based Platform

Author :
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (861 download)

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Book Synopsis A Mass Spectrometry Imaging-based Platform by :

Download or read book A Mass Spectrometry Imaging-based Platform written by and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mass spectrometry imaging (MSI) has evolved as a promising technology to map a broad range of molecules ranging from metabolites, peptides to proteins in an anatomical context. In this work, a multi-dimensional MSI-based platform was developed and applied to investigate several intriguing biological problems. This dissertation first introduces the rationale and recent progress of MSI, reviews its emerging applications to various fields and outlines one limitation that the detection of low molecular weight (MW) species is usually hindered by matrix-derived peaks. An ionless matrix referred as the proton sponge is therefore investigated as a solution to eliminate the interferences. It allows for probing metabolites in roots and root nodules of leguminous plants Medicago truncatula that possess symbiotic interactions with nitrogen-fixing rhizobia, highlighting differences in metabolic distribution between roots and nodules. In addition to exploring novel matrices, high resolution and high accuracy MSI (HRMSI) is also developed to circumvent matrix interferences by resolving endogenous analytes from background peaks. Novel spatial information of multiple metabolites and neurotransmitters is gleaned using rodent and crustacean brain specimens in this proof-of-principle study. Beyond metabolites, the HRMSI-based approach is applied to map neuropeptides in crustacean stomatogastric ganglia. Complementary to MALDI-MS, electrospray ionization (ESI)-MS-based experiments deliver another suite of neuropeptides. We therefore combine multiple MS instruments and compared their performances for characterization of novel neuropeptides from a marine model organism, the spiny lobster Panulirus interruptus. In addition to peptides, MALDI-MSI has also been applied to mapping protein distributions in the brain under pharmacological treatment. Specifically, alterations of protein expression patterns in the brains of infant rats were studied following neonatal exposure to the N-methyl-D-aspartate receptor antagonist dizocilpine (MK 801). A strategy combining profiling and imaging MS and top-down high-resolution tandem MS is utilized to discover putative protein biomarkers that may serve as potential targets of treatments for neurodevelopmental disorders. This work not only improves upon MSI by developing new methods, but also presents a useful platform that integrates MALDI-MSI with ESI-MS in exploring the underlying chemistry of various biological models exemplified by rodent, crustacean and plant-bacteria systems, and demonstrates wide applicability to future research.

Metabolomics in Neurodegenerative Disease

Author : Brian Green
Publisher : MDPI
ISBN 13 : 3039280406
Total Pages : 184 pages
Book Rating : 4.0/5 (392 download)

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Book Synopsis Metabolomics in Neurodegenerative Disease by : Brian Green

Download or read book Metabolomics in Neurodegenerative Disease written by Brian Green and published by MDPI. This book was released on 2020-04-21 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: The range of human neurodegenerative diseases continues to pose significant unmet medical needs for societies around the world. The progressive and terminal nature of these conditions places a considerable personal burden on the individual affected but also on public health systems and health services. Tens of millions of people are indiscriminately affected by various dementias, which are rising at an alarming rate. There are no cures for many conditions, and it is clear that treatments applied as early as possible could greatly improve outcomes for patients. Therefore, new disease classification and diagnostic tools should be a key priority. Metabolomics represents a relatively new field of analytical science, which can be extremely useful in the early diagnosis of disease. The relatively unique feature of metabolites is that they sit at the intersection between the genetic background of an organism and its environment. Because many neurodegenerative diseases are not genetically inherited (instead having a range of known genetic risk factors and also a large number of unknown environmental triggers) the field of metabolomics offers great promise for the discovery of new, biologically, and clinically relevant biomarkers for neurodegenerative disorders. It is already bringing forward new knowledge in terms of the mechanisms of neurodegenerative disease.

Biomarkers for Alzheimer's Disease Drug Development

Author : Robert Perneczky
Publisher : Springer Nature
ISBN 13 : 1071637746
Total Pages : 345 pages
Book Rating : 4.0/5 (716 download)

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Book Synopsis Biomarkers for Alzheimer's Disease Drug Development by : Robert Perneczky

Download or read book Biomarkers for Alzheimer's Disease Drug Development written by Robert Perneczky and published by Springer Nature. This book was released on 2024 with total page 345 pages. Available in PDF, EPUB and Kindle. Book excerpt: Zusammenfassung: This fully updated volume provides an up-to-date and comprehensive overview of the current state of technologies helping to accelerate Alzheimer's disease drug development. Addressing the latest advances in preclinical and clinical research, including new insights into the molecular mechanisms and emerging therapeutic strategies, the book continues by exploring digital biomarkers and advanced neuroimaging analysis which will transform how clinical trials in the Alzheimer's disease field are performed. Written for the highly successful Methods in Molecular Biology series, chapters feature the kind of detailed implementation advice that leads to greater success in the lab or clinic. Authoritative and practical, Biomarkers for Alzheimer's Disease Drug Development, Second Edition seeks to inspire and inform future efforts to develop effective treatments for this devastating disease

Development of Data Processing Methods for High Resolution Mass Spectrometry-based Metabolomics with an Application to Human Liver Transplantation

Download Development of Data Processing Methods for High Resolution Mass Spectrometry-based Metabolomics with an Application to Human Liver Transplantation PDF Online Free

Author : Olga Hrydziuszko
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (824 download)

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Book Synopsis Development of Data Processing Methods for High Resolution Mass Spectrometry-based Metabolomics with an Application to Human Liver Transplantation by : Olga Hrydziuszko

Download or read book Development of Data Processing Methods for High Resolution Mass Spectrometry-based Metabolomics with an Application to Human Liver Transplantation written by Olga Hrydziuszko and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Direct Infusion (DI) Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) is becoming a popular measurement platform in metabolomics. This thesis aims to advance the data processing and analysis pipeline of the DI FT-ICR based metabolomics, and broaden its applicability to a clinical research. To meet the first objective, the issue of missing data that occur in a final data matrix containing metabolite relative abundances measured for each sample analysed, is addressed. The nature of these data and their effect on the subsequent data analyses are investigated. Eight common and/or easily accessible missing data estimation algorithms are examined and a three stage approach is proposed to aid the identification of the optimal one. Finally, a novel survival analysis approach is introduced and assessed as an alternative way of missing data treatment prior univariate analysis. To address the second objective, DI FT-ICR MS based metabolomics is assessed in terms of its applicability to research investigating metabolomic changes occurring in liver grafts throughout the human orthotopic liver transplantation (OLT). The feasibility of this approach to a clinical setting is validated and its potential to provide a wealth of novel metabolic information associated with OLT is demonstrated.

Method Development and Application of Mass Spectrometry Imaging to Study Symbiotic Relationships Between Bacteria and Host Organisms

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Author :
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (949 download)

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Book Synopsis Method Development and Application of Mass Spectrometry Imaging to Study Symbiotic Relationships Between Bacteria and Host Organisms by :

Download or read book Method Development and Application of Mass Spectrometry Imaging to Study Symbiotic Relationships Between Bacteria and Host Organisms written by and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolic profiling can help shed light on cellular mechanisms; however a major technical challenge is to study endogenous metabolomic pathways without perturbing them. Most of the techniques currently in use for metabolomics studies in biological systems rely on tissue extracts which destroy the samples and result in the loss of information about analyte distribution within the tissue. Mass spectrometry imaging (MSI) has evolved as a promising technology to map a wide range of biomolecules in an anatomical context. In this dissertation, a multi-dimensional mass spectrometry-based platform was developed and applied to study interactions between bacteria and host organisms. Specifically, this work aimed to study the symbiotic relationship between soil bacteria and legume plants for agricultural and environmental sustainability applications, as well as the symbiosis between bacteria and leaf cutter ants and humans and our gut microbiota for the discovery of potentially novel antibiotics and antifungals. High-resolution, accurate-mass (HRAM) matrix-assisted laser desorption/ ionization (MALDI)-MSI was used to compare differentially treated biological samples, and liquid chromatography (LC)- electrospray ionization (ESI)- tandem mass spectrometry (MS/MS) coupled with database searching was used as a complementary mass spectrometry technique to identify interesting metabolites chosen from the MSI experiments. This work not only improves upon MSI by exploring novel sample preparation methods, but also presents a useful platform that integrates MALDI-MSI with ESI-MS in exploring the underlying chemistry of several biological symbiotic systems.

Method Development and Application of Mass Spectrometry-based Omics Analyses

Author : Pingli Wei
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (134 download)

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Book Synopsis Method Development and Application of Mass Spectrometry-based Omics Analyses by : Pingli Wei

Download or read book Method Development and Application of Mass Spectrometry-based Omics Analyses written by Pingli Wei and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Endogenous biomolecules, such as metabolites, neuropeptides, and proteins, play important roles in biological and physiological processes. Mass spectrometry (MS) has become a central technology for the study of biomolecules and their biological functions involved in disease mechanisms. However, there are still challenges for biomolecular analyses due to their poor ionization efficiency, low concentration, and various modifications. This dissertation is devoted to the development of novel and improved MS-based omics methodologies and the application to human disease studies. Specifically, this work established a multiplex isobaric dimethylated leucine (DiLeu) strategy combined with advanced bioinformatics tool for metabolomics studies and extended its application to biomarker discovery in mouse models for lower urinary tract symptoms (LUTS). This work also developed a novel MS approach for comparative neuropeptide characterization with a decision-tree driven MS method and applied it to peptidomic analyses of human pituitary tumors and subcommissural organ. Moreover, metabolomics, peptidomics, and proteomics were integrated to investigate how the host immune system is shaped by human microbiome during infection. In summary, this work not only improves current analytical methodologies for characterizing and quantifying biomolecules but also demonstrates its potential applications in the pharmaceutical industry and clinical settings.

Method Development and Application of Mass Spectrometry for Better Understanding of Disease Mechanisms and Diagnosis

Author : Yuan Liu (Ph. D.)
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (141 download)

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Book Synopsis Method Development and Application of Mass Spectrometry for Better Understanding of Disease Mechanisms and Diagnosis by : Yuan Liu (Ph. D.)

Download or read book Method Development and Application of Mass Spectrometry for Better Understanding of Disease Mechanisms and Diagnosis written by Yuan Liu (Ph. D.) and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mass spectrometry is a very powerful tool for identifying and quantifying biomolecules of interest, including metabolites, drug compounds, proteins, and post-translational modifications of (PTMs) of proteins. In mass spectrometry (MS)-based analytical techniques, liquid-chromatography coupled with tandem mass spectrometry (LC-MS/MS) is widely used for biomolecule analysis, including relative and absolute quantification of metabolites, proteins and PTMs. Data dependent acquisition (DDA) and data-independent acquisition (DIA) are two main methods for quantification of biomolecules in LC-MS/MS. By integrating isotopic and/or isobaric tags labeling, the DDA method enables precise absolute quantification and high-throughput analysis of biomolecules, facilitating biomarker discovery and elucidation of disease mechanisms. In contrast, DIA has garnered significant interest due to its exceptional reproducibility and depth in identifying and quantifying biomolecules. In this dissertation work, I apply these isotopic/isobaric tag labeling and label-free strategies to investigate potential biomarkers in the serum of Alzheimer's disease (AD) and colorectal cancer (CRC). Additionally, I explore the crosstalk between pancreatic stellate cells and pancreatic cancer cells using multi-faceted MS approaches.In addition to LC-MS/MS, mass spectrometry imaging (MSI) offers unparalleled insights into the spatial distribution of biomolecules across organs, tissues, and cell cultures, further enhancing our understanding of biological systems. We develop a tagging method to enhance the identification, quantification, and visualization of amine-containing metabolites by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Furthermore, I optimize a workflow for rapid sample preparation and high throughput MSI of biomolecule distribution in a widely used three-dimensional cell culture system - spheroids. In summary, the integration of various mass spectrometry techniques and method development discussed in this dissertation demonstrates that combining different mass spectrometry approaches can provide a more comprehensive molecular picture of the complex biological system, ultimately enhancing our understanding of disease mechanisms and advancing diagnosis and treatment options.