Metabolomics: Recent Advances and Future Applications

Foreword
Preface
Acknowledgments
Contents
Contributors
Introduction of Metabolomics: An Overview
	1 Introduction
	2 The “Omics”
	3 Why (and How) We Use Metabolomics to Answer Biological Questions
	4 Methodologies in Metabolomics
		4.1 Instrumentation
		4.2 The Mass Spectrometer
			4.2.1 The Ion Source
			4.2.2 The Mass Analyzer
			4.2.3 The Detector
		4.3 High-Resolution Mass Spectrometry (HRMS)
		4.4 The Mass Spectrum
		4.5 NMR
		4.6 FTIR
		4.7 Other Analytical Techniques
	5 Separation Techniques
		5.1 Liquid Chromatography
		5.2 Gas Chromatography
		5.3 Capillary Electrophoresis (CE)
		5.4 Ion Mobility Spectrometry (IMS)
	6 Sample Preparation
	7 Study Design
	8 Challenges in Metabolomics
		8.1 Challenges Common to All Omics
		8.2 Challenges Specific to Metabolomics
		8.3 Technical Hurdles to Metabolomics
	9 Conclusion
	References
Network Development and Comparison in Lipidomics and Metabolomics
	1 Introduction
	2 Network Development Methods
	3 Correlation-Based Methods for Molecular Network Derivation
	4 Classification-Based Methods
	5 Analysis of a Network
	6 Network Comparison Methods
	7 Overall Network Comparison
	8 Network Visualization
	9 Conclusions
	References
Analysis and Interpretation of Metabolite Associations Using Correlations
	1 Introduction
	2 Correlation Among Metabolites in Metabolomic Data
	3 Why Are Metabolites Correlated?
	4 Molecular Mechanisms Responsible for Observed Correlations in Replicate Experiments
	5 Measures of Association
		5.1 Pearson’s Correlation
			5.1.1 Testing the Significance of Correlations and Multiple Testing
			5.1.2 Robust Correlation Coefficients
		5.2 Spearman’s Correlation
		5.3 Kendall’s τ Correlation Coefficient
		5.4 Correlations and Data Pre-processing: Transformation and Normalization
		5.5 Mutual Information
	6 Which Measure of Association to Use?
	7 Comparing Correlations
		7.1 Comparing Two Correlations
		7.2 Averaging Correlations
		7.3 Analysis and Comparison of Correlation Matrices
	8 Conclusions
	References
Metabolomics Approach to Identify Biomarkers of Epidemic Diseases
	1 Introduction
	2 Top Spread Epidemics
	3 Communicable
		3.1 COVID-19
		3.2 Tuberculosis
		3.3 Malaria
		3.4 Dengue
		3.5 Typhoid
	4 Non-communicable Diseases
		4.1 Chronic Respiratory Diseases
		4.2 Cardiac Disorders
		4.3 Inflammatory Bowel Disease
		4.4 Liver Disorder
	5 Analytical Methods for Metabolomics
	6 MS Strategies for Large-Scale Metabolite Analysis
	7 Data Integration and Management Across Studies
	8 Conclusion
	References
Pharmacometabolomics: General Applications of Metabolomics in Drug Development and Personalized Medicine
	1 Introduction to Pharmacometabolomics
	2 Methods and Resources for Pharmacometabolomics Investigations
		2.1 Analytical Techniques
			2.1.1 Mass Spectrometry (MS)-Based Approaches
			2.1.2 Nuclear Magnetic Resonance (NMR)
		2.2 Repositories and Databases for Pharmacometabolomics Studies
	3 Pharmacometabolomics as an Innovative Solution for Enhancing the Discovery and Development of Novel Drugs
		3.1 Pharmacometabolomics as a Resourceful Tool in Drug Discovery and Development
			3.1.1 Target Identification
			3.1.2 Determining Mode of Action
			3.1.3 Drug Repurposing
			3.1.4 Drug Safety Evaluation
		3.2 Pharmacogenomic and Pharmacometabolomic Approaches in Studies of Drug Response Outcomes
		3.3 The Importance of Pharmacometabolomics for Predicting Patients’ Responses to Drugs
		3.4 The Role of Pharmacometabolomics in Adverse Drug Reactions
		3.5 Pharmacometabolomics and the Microbiome
	4 Applications of Pharmacometabolomics in Complex Diseases
		4.1 Breast and Lung Cancer
		4.2 Cardiovascular Disease
			4.2.1 Statins
			4.2.2 Aspirin
		4.3 Type 2 Diabetes Mellitus
		4.4 Neurological Diseases
	5 Conclusion
		5.1 Limitations and Future Directions of Pharmacometabolomics Research
			5.1.1 Study Design
			5.1.2 Sample Selection and Measurement of Metabolites
			5.1.3 Annotation of Metabolites
	6 Summary
	References
Microbial Metabolomics: An Overview of Applications
	1 Introduction
	2 Metabolomics on Microbial Monocultures
		2.1 Extraction Methods
		2.2 Nutrient Use
			2.2.1 Exometabolomics to Measure the Consumption of Nutrients
			2.2.2 Comparative Metabolomics to Identify Nutrient-Related Metabolic Pathways
			2.2.3 Stable Isotope Tracing to Track the Metabolic Fate of Nutrients
		2.3 Energy Conservation
			2.3.1 Measuring Energy Charge
			2.3.2 Respiration
			2.3.3 Fermentation and Overflow Metabolism
		2.4 Metabolism and Cell Replication
		2.5 Metabolic Flexibility and Adaptation
			2.5.1 Metabolic Adaptation to Nutrient Availability
			2.5.2 Metabolic Adaptation to Stress
			2.5.3 Metabolism and Antibiotics
		2.6 Discovery and Biosynthesis of Secondary Metabolites
			2.6.1 Monitoring the Products of Biosynthetic Gene Clusters
			2.6.2 Dereplicating Secondary Metabolites
			2.6.3 Linking Secondary Metabolites to Biosynthetic Gene Clusters
		2.7 Metabolic Engineering
			2.7.1 Reverse Metabolic Engineering
		2.8 Improving Culture Media
		2.9 Systems Microbiology: Towards Complete Metabolic Models
			2.9.1 Functional Gene Annotation
			2.9.2 Allosteric Regulation
	3 Metabolomics on Microbial Communities
		3.1 Studying Natural Isolates to Understand Complex Communities
		3.2 Synthetic Microbial Communities
		3.3 Gnotobiotic Animals
		3.4 Molecular Networking to Characterize Community Metabolomes
		3.5 Stable Isotope Tracing in Natural Communities
		3.6 Mass Spectrometry Imaging of Microbial Communities
		3.7 Integrating Omics Within Microbial Communities
			3.7.1 Metabolomics and Metagenomics
			3.7.2 Metabolomics and Metatranscriptomics
			3.7.3 Metabolomics and Metaproteomics
		3.8 Integrating Data Across Microbial Communities and Studies
		3.9 Predicting Community Metabolomes
	4 Conclusions
	References
Metabolomics in Autoimmunity, Infections, and Physiological Diseases
	1 Introduction
	2 Metabolomics in Autoimmune Diseases
		2.1 Metabolomics in Rheumatoid Arthritis (RA)
		2.2 Metabolomics in Systemic Lupus Erythematosus (SLE)
		2.3 Metabolomics in Inflammatory Bowel Disease (IBD)
	3 Metabolomics in Infectious Diseases
		3.1 Metabolomics in COVID-19
		3.2 Metabolomics in HIV Infection
		3.3 Metabolomics in Tuberculosis (TB)
	4 Metabolomics in Physiological Diseases
		4.1 Metabolomics in Cancer
		4.2 Metabolomics in Neurological Diseases
		4.3 Metabolomics in Cardiovascular Health and Diseases
	5 Future Perspectives
	References
Nutrimetabolomics: Metabolomics in Nutrition Research
	1 Introduction
	2 Metabolomics: A Multidisciplinary Approach
		2.1 Technical Approaches to Nutrimetabolomics and Analysis
			2.1.1 Targeted Metabolomics
			2.1.2 Untargeted Metabolomics
		2.2 Mass Spectrometry LC-MS Methods
	3 Analysis of Nutrimetabolomics Data
		3.1 Clustering Analysis
		3.2 Statistical Analysis Tools
		3.3 Functional Analysis Tools
		3.4 Nutrimetabolomics Modeling Tools
		3.5 Chemical Property Prediction Tools
	4 Computational Pipeline for Nutrimetabolomics
		4.1 R Packages and Software Tools for Nutrimetabolomics Studies
		4.2 R Codes for Importing and Visualization of Chemical Molecules Using R Packages
		4.3 R-Code for Preprocessing of Mass Spectrometry Imaging (MSI) Data Using MALDIquant
	5 Applications and Importance of Nutrimetabolomics
		5.1 Food Metabolome and Dietary Biomarkers
		5.2 In Physiological Monitoring of Diet and Nutrition Studies
			5.2.1 Requirement for Measuring Dietary Intake
			5.2.2 Requirements for Measuring Physical Activity and Sedentary Behavior
		5.3 In the Study of Diet-Related Diseases
			5.3.1 From Health to Disease Status
			5.3.2 Discovering Disease-Related Dietary Factors
	6 Role of Nutrimetabolomics in Precision Nutrition
		6.1 Deep Phenotyping: High-Quality Phenotypes to Stratify Obesity
		6.2 Metabolomics: Towards a Better Characterization of Eating
	7 Challenges and Future Prospects for Nutrimetabolomics
	8 Conclusion
	References
Metabolomics in Natural Product Discovery and Their Applications
	1 Introduction
	2 Metabolomics in NP Discovery
	3 Metabolomic Workflow
		3.1 Sample Preparation
		3.2 Analytical Methods of Purification and Quantitation of the Analyte of Interest
		3.3 Data Processing and Curation
	4 Applications of Metabolomics in NPs
		4.1 Dereplication of NPs
		4.2 Metabolic Map Profiling of NPs
		4.3 Quality Control (QC) of NPs
		4.4 Metabolomics in Revealing the Medicinal Properties of NPs
	5 Future Directions – Challenges and Prospects
	6 Conclusion
	References
Metabolomics Approach in Environmental Studies: Current Progress, Analytical Challenges, and Future Recommendations
	1 Introduction
	2 General Techniques in Environmental Metabolomics
	3 Environmental Exposure and Role of Metabolomics
		3.1 Pollutants Cause Changes in the Metabolome
		3.2 Natural Sources Cause Metabolomic Alterations: Climate Change, Pathogens, and Predation
		3.3 Fertilizer Exposure Disrupts Biological Mechanisms of Plants and Animals
		3.4 Model Organisms Allow for the Scientific Study of Environmental Factors
		3.5 Specific Compounds and Their Effects on Human Health
		3.6 Precision Environmental Health Monitoring
	4 Recent Advancements in Ecometabolomics and Biomonitoring
		4.1 Advancements in Conducting Field Experiments
		4.2 Advances in Biomonitoring and Bioassessment
	5 Challenges of Eco-Metabolomics
	6 Future Perspective of Environmental Metabolomic
		6.1 The Need for Standardizing Protocols
		6.2 Developing Reliable Databases
		6.3 Advance Applications of Metabolomics in Assessing Occupational Health Exposure
		6.4 Exposomes and Wearables
	7 Conclusion
	References
Deciphering Plant-Pathogen Interactions Through Plant Metabolomics: From Technical Advances to Applied Research
	1 Introduction
	2 Looking into Plant-Pathogen Interactions from a Metabolic Point of View
	3 Technical Advances in Plant Metabolomics
		3.1 Sample Preparation
		3.2 Advances in Analytical Methods and Techniques
		3.3 Metabolic Visualization Techniques: The Case of Mass Spectrometry Imaging
	4 Metabolomics Data Analysis and Omics Data Integration
	5 Breeding Programs: The Impact of Metabolome-Based Knowledge
	References
Metabolomics in Fundamental Plant Research
	1 Introduction
	2 Novel Gene Identifications and Their Functional Characterization for Crop Improvement
	3 Plant Species Identification
	4 Plant Root Metabolome and Climate Change
		4.1 Metabolome Changes in Roots by Abiotic Stress
		4.2 Metabolic Changes Associated with Root and Other Biotic Factor Interactions
	5 Plant Biomarker Identification
	6 Plant Single-Cell Metabolomics
	7 Concluding Remarks
	References
Spatial Metabolomics Using Imaging Mass Spectrometry
	1 Introduction
	2 Metabolomics
		2.1 Traditional Mass Spectrometry Analysis of Metabolome
	3 Imaging Mass Spectrometry (IMS) for Spatial Metabolomics
		3.1 Imaging Mass Spectrometry (IMS): The State of the Art
		3.2 Sample Preparation for IMS: Tissue Embedding
		3.3 Sample Preparation for IMS: Cryosectioning, Mounting, and Freeze-Drying
	4 Ionization Techniques Commonly Used for IMS
	5 Secondary Ion Mass Spectrometry (SIMS)
	6 Matrix-Assisted Laser Desorption/Ionization (MALDI)
		6.1 Application of Matrix for MALDI Imaging
		6.2 Enzymatic On-Tissue Digestion of FFPE Tissues for MALDI Imaging
	7 Desorption Electrospray Ionization (DESI)
	8 IMS Instrumentation: Technical Developments in Mass Resolution, Accuracy, and Selectivity
	9 Different Types of Mass Analyzers
	10 Ion Mobility Separation
	11 Tandem Mass Spectrometry
	12 Identification Strategies for Metabolites, Peptides, and Proteins
	13 Image Generation and Data Analysis
	14 Applications of Imaging Mass Spectrometry in Cancer Research
	15 Applications of Imaging Mass Spectrometry in Drug Imaging
	16 Concluding Remarks
	References
Future Perspectives of Metabolomics: Gaps, Planning, and Recommendations
	1 Introduction
	2 Metabolomics for the Masses
		2.1 Physiological Assessment Through Endogenous Molecules
		2.2 Limitations of Current Technologies
			2.2.1 Exogenous Molecule Identification
			2.2.2 Commercial Affordability and Interest
	3 Future Opportunities and Challenges in Translational Metabolomics
	4 Metabolomics as a tool to Accelerate Therapeutics and Novel Drug Discoveries
	5 AI-/ML-Based Approaches for Metabolomics Data Mining and Analysis
	6 Single-Cell Metabolomics
		6.1 Current Single-Cell Metabolomics Technologies
		6.2 The Future of Single-Cell Metabolomics
	7 Metabolic Sensors and the Future of Healthcare
	8 Recommendations
	9 Conclusion
	References
Index