Metabolomics and Its Impact on Health and Diseases

Preface
Contents
Practical Aspects of NMR-Based Metabolomics
1 Introduction
2 A Short History of NMR-Based Metabolomics
3 Practical Aspects of NMR-Based Metabolomics
3.1 Sample Preparation
3.2 Choosing the Right Pulse Sequence
3.3 Spectral Acquisition and Processing
4 Data Analysis
4.1 Data Analysis for Targeted Metabolomics
4.2 Data Analysis for Untargeted Metabolomics
4.3 Targeted or Untargeted?
5 Biological Interpretation
6 Conclusion and Future Prospects
References
Compound Identification Strategies in Mass Spectrometry-Based Metabolomics and Pharmacometabolomics
1 Introduction
2 Step 1: Study Design: Define Compound Identification Goals
3 Step 2: Acquire Data - Experimental Strategies to Identify Compounds in Metabolomics Data
4 Step 3: Computational Strategies for Data Cleaning and Feature Annotation
5 Step 4: MS/MS Libraries and Compound Identification Using Library Search
6 Step 5: Assess and Report Identification Confidence
7 Conclusion: Pharmacology-Focused Compound Identification
References
Metabolomics and NMR
1 Objectives
2 Brief History
2.1 Potential
2.1.1 A Warning
2.2 Definitions
2.2.1 Metabolome
2.2.2 Metabo -Nomics or -Lomics
More ``-Omics´´?
2.2.3 Metabolites
3 Expectations
3.1 Reality
3.1.1 Key Considerations for NMR
4 NMR and MS
4.1 Complementation: Can We Just Skip to the End?
4.2 Metabolomics via Mass Spectrometry
4.3 Metabolomics by NMR
5 Nuclear Magnetic Resonance Spectroscopy
5.1 NMR Experiment for Metabolomics
5.1.1 First Impressions
Note
5.2 Liquids NMR
Note
5.2.1 Progression to Metabolomics
Minimizing Problems
5.3 Samples
5.3.1 Preparation
Note
Note
5.3.2 NMR Tubes, Spinners, and Side-Bands
Note
Additionally
5.3.3 Gathering and Handling
Volunteers
Note
Long-Term Studies and Storage
Note
Note
Note
5.3.4 In the Tube
Note
5.4 NMR Spectrometer
5.4.1 Probe
Note
Cryogenically Cooled Probes
Note
5.4.2 Console
Note
5.4.3 Host Computer
5.4.4 Experiment Pulse Sequence
Note
5.4.5 Parameters
Error Bars and Statistical Relevance
5.4.6 Phase Cycle
Note
5.4.7 Temperature Calibration
Note
Note
Robotic Sample Handling
5.4.8 Tune/Match
Note
5.4.9 Excitation Pulse
Note
5.4.10 Gain
Note
5.4.11 Pulse Field Gradients
Note
5.5 Manuscript Reporting Parameters
5.5.1 Pulse Width
Note
5.5.2 Delays: Relaxation, Equilibrium
Note
5.5.3 Post-Acquisition: Weighting Function
Note
5.5.4 Corrections: Linear Prediction, Baseline, Phasing
Note
5.5.5 Referencing
Note
6 Future Ideas
6.1 Solids NMR Metabolomics
6.2 Working with Raw FID
6.3 PureShift 1H-1H J-Coupling Removal
7 Conclusion
Appendix A: Example Pulse Sequence: Metabolomics 1D-1H ``Metnoesy´´
Appendix B: Example Experimental Section
Experimental Section
NMR Samples
NMR Spectroscopy
References
Natural Products Drug Discovery: On Silica or In-Silico?
1 Introduction
2 Chemical Profiling Techniques in Metabolomics
3 Statistical Methods to Correlate Between Chemical Profiles and Bioactivity
3.1 Correlation with a Simplified Dataset: Discriminant Analysis
3.2 Correlation Analysis with Non-Discriminant Variables
4 Application of Metabolomics-Based Bioactivity to Various Disease Models
4.1 Antimicrobial Activity
4.2 Anticancer Activity
4.3 Anti-inflammatory Activity
5 Conclusions and Perspective
References
Quantitative NMR Methods in Metabolomics
1 Introduction
2 Quantitation Approaches Using NMR
2.1 Internal Reference Standards for Absolute Quantitation
2.2 Alternative Reference Standards for Absolute Quantitation
2.3 Quantitation of Metabolites Using Intact Samples
2.3.1 Intact Serum and Plasma Analysis
2.3.2 Intact Urine Analysis
2.3.3 Intact Tissue Analysis
2.4 Metabolite Quantitation Using Processed Samples
2.4.1 Analysis of Aqueous Metabolites
2.4.2 Analysis of Coenzymes and Antioxidants
2.4.3 Analysis of Lipids
2.5 Quantitation Methods Using Stable Isotope Labeling
2.5.1 Isotope Labeling Focused on Metabolic Fluxes and Pathways
2.5.2 Isotope Labeling Focused on Metabolite Analysis
3 Conclusion
References
Advancements in Pulsed Stable Isotope-Resolved Metabolomics
1 Introduction: A Brief History of Isotopic Labelling
2 Time- and Isotope-Resolved Metabolomics
2.1 Stable Isotope-Resolved Metabolomics
2.2 Time Resolved Isotope Labelling Studies
2.3 Isotope Tracing at the Crossroad of Metabolic Pathways
2.4 The Application of Ultra-High Resolution Mass Spectrometry Allows the Tracing of Different Isotopic Species
3 Applications and Future Perspectives
3.1 Applications of pSIRM
3.2 Perspective Towards Single Cells
References
Metabolomics in Cell Biology
1 Introduction
1.1 Omics Context
1.2 History of Metabolomics Using Cellular Samples
2 Metabolomics Approaches: Targeted vs. Untargeted
2.1 Sample Types
2.2 Preparation of Cell Extracts for Metabolomics
2.3 Metabolomics Technologies
2.3.1 NMR-Based Methods
2.3.2 MS-Based Methods
3 Case Studies
3.1 Examples of Cancer Metabolomics
3.2 Real-Time Measurements of Cells
3.3 Metabolic Studies in Mycobacteria
3.4 Metabolic Fluxes by NMR and GC-MS
3.5 Examples for Fluxes in Cancer Cells by GC-MS
3.6 Fluxes and Metabolic Modelling
3.7 Metabolic Fluxes in Liver Disease
4 Conclusions
References
NMR-Based Metabolomics to Evaluate Individual Response to Treatments
1 Introduction
1.1 The Individual Metabolic Phenotype
1.2 Modulation of the Individual Metabolic Phenotype
2 Disease Fingerprinting and Individual Response to Pharmacological Therapy
2.1 Celiac Disease
2.2 Cancer
2.2.1 Breast Cancer
Response to Chemotherapy
Disease Recurrence
2.2.2 Lung Cancer
Response to Immunotherapy
2.2.3 Colon Cancer
Disease Recurrence
Pre-Surgical Effects of Anesthesia
2.3 Viral Infections
2.3.1 Hepatitis
2.3.2 COVID-19
2.4 Chronic Obstructive Pulmonary Disease
2.5 Drug Toxicity
References
Pharmacometabolomics of Asthma as a Road Map to Precision Medicine
1 Introduction
2 Pharmacometabolomics
3 Applications of Pharmacometabolomics to Asthma
4 Metabolomic Responses to Asthma Therapeutics
4.1 Steroids (Inhaled and Oral)
4.2 Bronchodilators (Beta-Agonists)
4.3 Leukotriene Inhibitors
4.4 Combined Therapeutics
5 Therapy or Severity
6 Clinical Subgroups and Endotypes
6.1 Clinically Derived Subgroups (The ``Bottom-Up´´ Approach)
6.2 Omic-Driven Endotypes (The ``Top-Down´´ Approach)
6.3 Aspirin-Exacerbated Asthma
7 Prevention
8 Challenges of Pharmacometabolomics in Asthma
9 Conclusions
References
Prospective Metabolomic Studies in Precision Medicine: The AKRIBEA Project
1 Metabolomics as a Tool for Precision Medicine
1.1 Precision Medicine and Molecular Medicine
1.2 Biomarkers and Metabolomics
1.3 Description of the Accessible NMR Metabolic Landscape
1.4 On the Cohort Size for Applications in Precision Medicine
2 Large-Cohort Sample Collection and Biobanking for Metabolomic Studies
3 Standard Operating Procedures for Metabolomics in Precision Medicine
4 Artificial Intelligence and Data Mining: Data Is the Way
4.1 Data Management
4.2 Data Analysis
4.3 Biological Contextualization
4.4 From the Laboratory to the Clinic
5 Applications of Precision Medicine: Non-oriented and Oriented Metabolomics Analysis
5.1 Non-oriented Metabolomics Study: Metabolic Syndrome
5.2 Oriented Metabolomics Study: COVID-19
6 Concluding Remarks
References
Chemotherapy-Induced Peripheral Neuropathy
1 Introduction
2 Review of CIPN Metabolomics
2.1 Metabolomics Analyses Design
2.2 CIPN Study Design
2.3 Clinical CIPN Metabolomics Studies
2.4 Animal and Cellular CIPN Metabolomics Studies
2.5 Summary
3 Investigation of Peripheral Neuropathy Metabolomic Biomarker Pathways
3.1 Histidine
3.1.1 1-Methylhistidine
3.1.2 Carnosine
3.1.3 Ergothioneine
3.1.4 Histamine
3.1.5 Summary
3.2 Phenylalanine
3.2.1 Phenylalanine and Tyrosine
3.2.2 Phenethylamine
3.2.3 Summary
3.3 N-Acetylornithine
3.3.1 Ornithine and Arginine
3.3.2 Ornithine and Polyamines: Putrescine, Spermidine, and Spermine
3.3.3 Summary
3.4 Threonine
3.5 Glycogen
3.6 Adenosine Phosphates
4 Conclusion
References
Metabolomics of Respiratory Diseases
1 Introduction
2 Respiratory Diseases with Metabolomic Signatures
2.1 Asthma
2.2 Chronic Obstructive Pulmonary Disease (COPD)
2.3 Pneumonia
2.4 Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
2.5 Occupational and Environmental Lung Diseases
3 Metabolomics of Lung Microbiome in Respiratory Diseases
3.1 Asthma
3.2 Chronic Obstructive Pulmonary Disease (COPD)
4 Conclusive Remarks
References
The Metabolomics of Critical Illness
1 Introduction: A Potential Role for Metabolomics in Understanding Critical Illness
2 Metabolic Alterations in Critical Illness
3 Endocrine Drivers of Altered Metabolism
4 Adrenergic Mediators and Their Changes in Critical Illness
5 Inflammatory Mediators (Cytokines) and Their Contribution to Metabolism
6 Metabolic Phases During Critical Illness
7 Autophagy and Mitophagy
8 Nutrient Changes During Critical Illness
8.1 Lactate: The Original Metabolomic Biomarker
9 Metabolomics in Sepsis
9.1 Diagnosis of Sepsis
9.2 Prognostication in Sepsis
9.3 Future Directions: Using Metabolomics to Guide Treatment
10 Metabolomics Studies in ARDS
10.1 Blood Metabolomics of ARDS
10.2 Using Blood Metabolomics to Identify High-Risk Subsets of ARDS Cohorts
10.3 Pulmonary Specific Samples for Metabolomic Profiling
11 Metabolomics of Critical Illness: Future Directions
References