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Book Details
Abstract
In the rapidly growing field of metabolomics, a comprehensive book describing the state of the art in the application of NMR spectroscopy will be a key title for practitioners. Providing a unique resource of background knowledge, resources, instrumental platforms and software, this book will introduce relevant theory to the researcher as well as serve as a practical guide detailing key experiments and data handling procedures. Information available on common sample types will be described together with reference to the latest web-based resources available. Application-specific considerations will be discussed for a wide range of research topics. Written by an expert team as a service to the metabolomics community, this book will appeal to NMR spectroscopists, analytical chemists and biochemists especially those with an interest in medical applications.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| NMR-based Metabolomics | i | ||
| Preface | v | ||
| Acknowledgements | vii | ||
| Contents | ix | ||
| Chapter 1 - Instrumental Platforms for NMR-based Metabolomics | 1 | ||
| 1.1 History of NMR Hardware Development | 1 | ||
| 1.2 Components of NMR Hardware | 3 | ||
| 1.2.1 Magnet | 3 | ||
| 1.2.2 Shim Coils | 4 | ||
| 1.2.3 Sample Probe | 4 | ||
| 1.2.3.1 Radiofrequency Coils | 5 | ||
| 1.2.3.2 Cryoprobes | 5 | ||
| 1.2.3.3 Microprobes | 6 | ||
| 1.2.3.4 Flow Injection Probes | 6 | ||
| 1.2.3.5 Magic-angle Spinning Probes | 8 | ||
| 1.2.4 Digital Filtering | 8 | ||
| 1.2.5 Computational Support to Hardware | 9 | ||
| 1.2.5.1 Databases | 9 | ||
| 1.2.5.2 Laboratory Information Management Systems | 10 | ||
| 1.2.5.3 Metabolic Modelling | 10 | ||
| 1.3 Automation of Metabolomic Profiling | 10 | ||
| 1.3.1 Sample Preparation | 11 | ||
| 1.3.1.1 Robotics for Sample Preparation | 12 | ||
| 1.3.2 Automated NMR | 13 | ||
| 1.3.2.1 Hardware for Automation | 14 | ||
| 1.3.2.2 Temperature Control | 16 | ||
| 1.3.3 Automated Acquisition | 16 | ||
| 1.3.3.1 Instrumental Calibration | 17 | ||
| 1.3.3.2 ERETIC | 17 | ||
| 1.3.3.3 Automation Sequences | 18 | ||
| 1.3.4 Integrated Metabolic Profiling NMR Systems | 19 | ||
| References | 20 | ||
| Chapter 2 - NMR Pulse Sequences for Metabolomics | 22 | ||
| 2.1 Introduction | 22 | ||
| 2.2 Standard 1D NMR Pulses Sequences for High-throughput Metabolomics | 23 | ||
| 2.2.1 One-dimensional 1H NOESY Experiment | 23 | ||
| 2.2.2 The Carr–Purcell–Meiboom–Gill (CPMG) Experiment | 25 | ||
| 2.2.3 Diffusion-edited NMR Spectroscopy | 25 | ||
| 2.3 Water and Solvent Suppression for NMR of Biofluids | 27 | ||
| 2.3.1 Water Pre-saturation | 27 | ||
| 2.3.2 Advanced Water Suppression Schemes | 28 | ||
| 2.4 Multidimensional NMR Techniques for Metabolite Identification and Quantification | 28 | ||
| 2.4.1 Proton Homonuclear Correlation Spectroscopy | 29 | ||
| 2.4.2 2D 1H–13C Heteronuclear Correlation Experiments | 31 | ||
| 2.4.3 Metabolite Quantification from Two-dimensional NMR | 32 | ||
| 2.5 Novel Strategies for Fast NMR Data Acquisition in Metabolomics | 33 | ||
| 2.5.1 Non-uniform Sampling | 33 | ||
| 2.5.2 Fast Targeted Multidimensional NMR Spectroscopy | 33 | ||
| 2.5.3 Ultrafast 2D NMR for Metabolite Quantification | 36 | ||
| 2.6 Conclusion | 37 | ||
| References | 37 | ||
| Chapter 3 - NMR Spectroscopy of Urine | 39 | ||
| 3.1 Introduction | 39 | ||
| 3.1.1 NMR Spectra of Urine and Conventional Normalization to Creatinine | 40 | ||
| 3.1.2 Early Applications: Urine NMR Metabolomics in Toxicology | 43 | ||
| 3.1.3 Analytical Reproducibility of Urine NMR Spectra | 46 | ||
| 3.1.3.1 Analytical Reproducibility in the COMET Project | 46 | ||
| 3.1.3.2 Analytical Reproducibility in the INTERMAP Study | 47 | ||
| 3.2 NMR Spectroscopy of Urine in Metabolomics Studies | 48 | ||
| 3.2.1 Collection and Storage of Urine Samples | 48 | ||
| 3.2.1.1 Urine from the Typical Human Adult | 48 | ||
| 3.2.1.1.1\rRestrictions on Subjects’ Pre-collection Dietary and Behavioral Activities.Sources of urine NMR spectral variation arising from ... | 49 | ||
| 3.2.1.1.2 Considerations for Time Duration of Sample Collection.In metabolomics studies, it is often desirable to collect the complete qua... | 50 | ||
| 3.2.1.1.3\rConsiderations for Sample Post-collection Addition of Preservatives and Freezing.Human urine samples are stable for at least 26 ... | 50 | ||
| 3.2.1.2 Urine from Human Infants | 52 | ||
| 3.2.1.3 Urine from Rodents and Other Experimental Animals | 52 | ||
| 3.2.2 Preparation of Urine Samples for NMR | 53 | ||
| 3.2.2.1 Urinary NMR Sample Volume, Concentration, and Additives | 53 | ||
| 3.2.2.2 Control of pH, Ion Concentration, and Dication Complex Formation | 54 | ||
| 3.2.2.3 Utilization and Preparation of Synthetic Urine Samples | 56 | ||
| 3.2.3 Recommendations Pertaining to Urine Sample Collection, Storage and Treatment with a Focus on Diagnostic Study | 56 | ||
| 3.2.4 One-dimensional NMR Experiments and Suppression Methods for Use with Urine | 57 | ||
| 3.2.5 Two-dimensional NMR Experiments and Suppression Methods for Use with Urine | 59 | ||
| 3.2.6 Normalization of Urine NMR Spectral Datasets | 60 | ||
| 3.2.7 Multivariate Statistical Analysis of NMR Urine Spectra | 63 | ||
| 3.3 NMR Spectroscopy of Urine: Systems Biology Applications | 66 | ||
| 3.3.1 Metabolite Variation in Urine from Healthy Subjects | 66 | ||
| 3.3.2 Metabolite Variation in Urine Between Healthy Population Groups | 66 | ||
| 3.3.3 Unhealthy Pathophysiologies, Disease Diagnosis, and Pharmacometabolomics | 70 | ||
| 3.4 Conclusion | 72 | ||
| References | 73 | ||
| Chapter 4 - NMR Spectroscopy of Serum and Plasma | 85 | ||
| 4.1 Introduction | 85 | ||
| 4.1.1 Sample Composition and Metabolome Coverage | 86 | ||
| 4.2 Methodology | 89 | ||
| 4.2.1 Comparison of Sample Preparation Methods | 90 | ||
| 4.2.2 Data Acquisition | 94 | ||
| 4.2.2.1 Routine 1D 1H NMR Analysis | 94 | ||
| 4.2.2.2 2D NMR 1H Analysis | 95 | ||
| 4.2.2.3 Lipoprotein Analysis | 96 | ||
| 4.2.2.4 Diffusion Spectroscopy | 99 | ||
| 4.2.2.5 Glycoproteins | 101 | ||
| 4.2.2.6 Lipid Extracts of Serum | 102 | ||
| 4.2.2.7 Metabolite Quantification and Automated Spectral Analysis | 103 | ||
| 4.3 Applications | 105 | ||
| 4.3.1 Sample Collection and Pre-analytical Variation | 105 | ||
| 4.3.1.1 Sample Type and Spectral Contaminants | 105 | ||
| 4.3.1.2 Time and Temperature Prior to and During Centrifugation | 106 | ||
| 4.3.1.3 Storage Time and Temperature | 107 | ||
| 4.3.2 Confounding and Normal Variation | 107 | ||
| 4.3.3 Cancer | 108 | ||
| 4.3.4 Cardiovascular Disease | 110 | ||
| 4.3.5 Diabetes Risk | 112 | ||
| 4.3.6 Genetic Influences on the Serum NMR Metabolome | 113 | ||
| 4.3.7 Toxicology | 114 | ||
| 4.4 Future Perspectives | 115 | ||
| References | 116 | ||
| Chapter 5 - High-resolution Magic-angle Spinning (HR-MAS) NMR Spectroscopy | 133 | ||
| 5.1 Introduction | 133 | ||
| 5.2 HR-MAS Basic Concepts | 134 | ||
| 5.2.1 Magnetic Susceptibility Broadening | 134 | ||
| 5.2.2 Magic-angle Spinning | 136 | ||
| 5.3 Hardware and Practical Considerations | 138 | ||
| 5.3.1 Magnetic Susceptibility Components | 138 | ||
| 5.3.2 B0 Field Correction | 138 | ||
| 5.3.3 B0 Field Locking | 140 | ||
| 5.3.4 Sample Temperature | 140 | ||
| 5.3.5 Pulse-field Gradient | 140 | ||
| 5.3.6 Pulse Experiments | 141 | ||
| 5.4 Recent (HR)-MAS Developments Towards NMR-based Metabolomics | 142 | ||
| 5.4.1 In vivo Studies | 142 | ||
| 5.4.2 Slow MAS Experiments | 142 | ||
| 5.4.3 Magic-angle Field Spinning | 144 | ||
| 5.4.4 Microscopic Quantity | 145 | ||
| 5.5 Concluding Remarks | 147 | ||
| Acknowledgements | 147 | ||
| References | 147 | ||
| Chapter 6 - Investigation of Tumor Metabolism by High-resolution Magic-angle Spinning (HR-MAS) Magnetic Resonance Spectroscopy (MRS) | 151 | ||
| 6.1 HR-MAS MRS for Studies of Metabolic Abnormalities in Cancer | 151 | ||
| 6.2 HR-MAS MRS in Metabolic Profiling of Intact Tumor Tissue—Clinical Studies | 154 | ||
| 6.2.1 Breast Cancer | 154 | ||
| 6.2.2 Prostate Cancer | 154 | ||
| 6.2.3 Brain Tumors and Brain Metastases | 155 | ||
| 6.2.4 Other Cancer Types | 156 | ||
| 6.3 HR-MAS MRS in Metabolic Profiling of Intact Tumor Tissue—Preclinical Disease Models | 157 | ||
| 6.4 Technology Developments and Optimized Protocols for HR-MAS MRS Analysis | 158 | ||
| 6.4.1 Tissue Sampling and Harvesting | 158 | ||
| 6.4.2 Protocols and Sequences | 158 | ||
| 6.4.3 Quantification of Metabolites Using HR-MAS MRS | 159 | ||
| 6.4.4 Multivariate Analysis | 160 | ||
| 6.4.5 Correlation with in vivo Spectroscopy | 160 | ||
| 6.4.6 HR-MAS MRS and Gene Expression Analysis | 161 | ||
| 6.5 HR-MAS MRS of X-Nuclei | 161 | ||
| 6.5.1 13C HR-MAS MRS | 161 | ||
| 6.5.2 31P HR-MAS MRS | 162 | ||
| 6.6 Future Prospects of HR-MAS MRS in Cancer Metabolomics | 162 | ||
| References | 163 | ||
| Chapter 7 - NMR in Environmental and Nutritional Research | 168 | ||
| 7.1 Introduction | 168 | ||
| 7.2 NMR-based Analytical Methods in Environmental and Nutritional Research | 170 | ||
| 7.2.1 Sample Types | 170 | ||
| 7.2.2 Common NMR Spectroscopy Experiments | 171 | ||
| 7.2.3 Practical Aspects of NMR Spectroscopic Analysis in Nutritional and Environmental Research | 171 | ||
| 7.3 Applications of NMR-based Metabolomics in Nutritional Research | 173 | ||
| 7.3.1 Nutritional Exposure Characterisation—Compositional Analysis of Foodstuffs | 173 | ||
| 7.3.2 NMR-based Biomarkers of Food Consumption | 174 | ||
| 7.3.3 Assessing the Influences of Diet on the Metabolome | 176 | ||
| 7.4 Application of NMR-based Metabolomics in Environmental Health Research | 177 | ||
| 7.4.1 Environmental Exposure Characterisation | 177 | ||
| 7.4.2 Deriving Biomarkers of Environmental Exposure | 178 | ||
| 7.4.3 Assessing the Influences of the Environment on the Metabolome | 178 | ||
| 7.5 Summary | 179 | ||
| References | 180 | ||
| Chapter 8 - NMR Foodomics | 183 | ||
| 8.1 Introduction to NMR Analysis of Food | 183 | ||
| 8.2 Sampling and Measuring Food with NMR | 186 | ||
| 8.3 Data Analysis in NMR Foodomics Studies | 193 | ||
| 8.3.1 Use PCA | 195 | ||
| 8.3.2 Use Alignment | 195 | ||
| 8.3.3 Use Intervals | 197 | ||
| 8.3.4 Use Test Set and ROC | 199 | ||
| 8.3.5 Use ASCA to Explore Designed Experiments | 200 | ||
| 8.4 Selected NMR Foodomics Studies | 202 | ||
| 8.4.1 Wine | 202 | ||
| 8.4.1.1 Case Study: La Rioja Terroir | 205 | ||
| 8.4.2 Olive Oil | 205 | ||
| 8.4.2.1 Case Study: Geographical Origin of Olive Oils | 207 | ||
| 8.4.3 Tomato | 207 | ||
| 8.4.3.1 Case Study: Authenticity of Pomodoro di Pachino | 209 | ||
| 8.4.4 Alginate | 210 | ||
| 8.4.4.1 Case Study: The Mannuronic:Guluronic Ratio | 212 | ||
| 8.4.5 Milk | 213 | ||
| 8.4.5.1 Case Study: Milk Differentiation Between Cow Breeds | 215 | ||
| 8.4.6 Cheese | 219 | ||
| 8.4.6.1 Case Study: Fiore Sardo Cheese Production | 220 | ||
| 8.4.7 Fish | 221 | ||
| 8.4.7.1 Case Study: The Aquaculture of Gilthead Sea Bream | 223 | ||
| 8.4.8 Meat | 225 | ||
| 8.4.8.1 Case Study: Parma Ham and Sausages—Fat Composition | 226 | ||
| 8.5 Foodomics Outreach | 226 | ||
| References | 228 | ||
| Chapter 9 - NMR-based Metabolomics: Understanding Plant Chemistry and Identification of Biologically Active Compounds | 246 | ||
| 9.1 Introduction | 246 | ||
| 9.2 What Is the Metabolome | 248 | ||
| 9.2.1 Selective Extraction | 248 | ||
| 9.2.2 The Metabolomics Process | 248 | ||
| 9.3 Plant Under Stress | 249 | ||
| 9.3.1 Host Plant Resistance | 249 | ||
| 9.3.2 Biotic/Abiotic Stress | 251 | ||
| 9.3.3 Species Characterization: Chemotaxonomy | 251 | ||
| 9.4 Metabolomics to Evaluate Synergy | 252 | ||
| 9.5 Bioactivity Screening | 253 | ||
| 9.6 Food Metabolomics | 255 | ||
| 9.7 Single-cell Metabolomics | 256 | ||
| 9.7.1 Limitations of Single-cell Metabolomics | 258 | ||
| 9.8 Conclusions | 259 | ||
| References | 259 | ||
| Chapter 10 - 1H NMR-based Metabolic Profiling in Infectious Disease Research | 264 | ||
| 10.1 Introduction | 264 | ||
| 10.2 Human and in vivo Studies | 267 | ||
| 10.2.1 Diagnostic and Prognostic Biomarkers | 267 | ||
| 10.2.2 HIV/AIDS, Tuberculosis, and Malaria | 268 | ||
| 10.2.3 Neglected Tropical Diseases | 269 | ||
| 10.3 Systemic Characterisation of Parasite Effects in vivo | 273 | ||
| 10.3.1 Global Metabolic Changes in the Murine Host | 273 | ||
| 10.3.2 Immune–Metabolic Co-development | 273 | ||
| 10.4 In vitro Studies | 274 | ||
| 10.5 Conclusions | 276 | ||
| References | 277 | ||
| Chapter 11 - Imaging Metabolic Processes in Living Systems with Hyperpolarised 13C Magnetic Resonance | 280 | ||
| 11.1 Hyperpolarisation | 280 | ||
| 11.2 Dynamic Nuclear Polarisation | 283 | ||
| 11.3 Magnetic Resonance Detection of Hyperpolarised Metabolites | 286 | ||
| 11.4 Deriving Kinetic Parameters | 291 | ||
| 11.5 Biomedical Applications of DNP | 295 | ||
| 11.6 Hyperpolarised 13C Imaging in vivo | 299 | ||
| References | 303 | ||
| Chapter 12 - Advances in Computational Analysis of Metabolomic NMR Data | 310 | ||
| 12.1 Introduction | 310 | ||
| 12.2 Bayesian Methods in NMR Data Processing | 311 | ||
| 12.3 Developments in Statistical Correlation Analysis | 313 | ||
| 12.4 Statistical Association Networks | 313 | ||
| 12.5 Genetic Mapping of Metabolic Phenotypes | 317 | ||
| 12.5.1 mQTL Mapping Workflow | 317 | ||
| 12.5.2 Lessons Learnt from mQTL Studies | 318 | ||
| 12.6 The Role of Data Standards | 319 | ||
| References | 320 | ||
| Chapter 13 - NMR Spectroscopy of Cell Culture, Tissues, and Other Biofluids | 324 | ||
| 13.1 General Introduction | 324 | ||
| 13.2 Sampling, Extraction and Analysis of Cellular Material | 325 | ||
| 13.2.1 Introduction | 325 | ||
| 13.2.2 Sampling Cellular Material | 327 | ||
| 13.2.3 Quenching Metabolism | 329 | ||
| 13.2.4 Extraction of Intracellular Metabolites | 330 | ||
| 13.2.4.1 Physical Extraction | 330 | ||
| 13.2.4.2 Chemical Extraction | 331 | ||
| 13.2.5 NMR Spectroscopy of Cellular Materials | 334 | ||
| 13.3 Cellular Material Profiling Applications | 336 | ||
| 13.4 Other Biofluids | 338 | ||
| 13.4.1 Introduction | 338 | ||
| 13.4.2 Faeces | 341 | ||
| 13.4.3 Cerebrospinal Fluid | 343 | ||
| 13.4.4 Milk | 345 | ||
| 13.4.5 Seminal Fluid | 348 | ||
| 13.4.6 Bile | 349 | ||
| 13.4.7 Less Commonly Reported Biofluids | 352 | ||
| 13.5 Summary and Future Developments | 352 | ||
| Acknowledgements | 353 | ||
| References | 353 | ||
| Subject Index | 360 |