Clinical Metabolomics Applications in Genetic Diseases

Contents
The Advanced Technology and Clinical Application in Metabolomics
1 Introduction
2 Mass Spectrometry
3 Nuclear Magnetic Resonance
4 Metabolomics Data Analysis
5 Advancement of Metabolomics Application in Clinical Research
5.1 Oncology
5.2 Prenatal Medicine
6 Frontiers in Metabolomics
References
Mass Spectrometry-Based Metabolomics for the Clinical Laboratory
1 Introduction
2 Components of a Mass Spectrometer
2.1 Sample Ionization
2.2 Mass Analyzers
2.2.1 Quadrupole
2.2.2 Triple Quadrupole
2.2.3 TOF
2.2.4 Ion Traps
3 Chromatographic Separations Interfacing with MS
3.1 Liquid Chromatography
3.2 Gas Chromatography
3.3 Capillary Electrophoresis
3.4 Ion Mobility Spectrometry
4 Current Clinical Metabolomic Applications
5 Guidance Documents and Validation Hurdles
6 Summary and Future Outlook
References
Metabolomics: A Pipeline for Biomarker Discovery in Genetic Diseases
1 Introduction
2 Sample Preparation in Metabolomics
2.1 Sample Collection
2.2 Sample Type
2.3 Metabolite Extraction
3 Technologies Used in Metabolomics
3.1 Mass Spectrometry (MS)
3.2 Nuclear Magnetic Resonance (NMR) Spectroscopy
4 Metabolite Identification and Statistical Analysis
5 Approaches Followed in Metabolomics for Biomarker Discovery
5.1 Untargeted Approach
5.2 Targeted Approach
6 Biomarker Discovery and Validation
7 Application of Metabolomics in Disease Biomarker Discovery in Genetic Disorders
7.1 Cystic Fibrosis
7.2 Down Syndrome
7.3 Sickle Cell Disease
7.4 Glycogen Storage Disorders
8 Current Trends and Future Perspective
9 Conclusions
References
Bioinformatic Tools for Clinical Metabolomics
1 Introduction
2 Bioinformatic Tools for Metabolite Identification
2.1 Bioinformatic Tools for Metabolite Identification Via NMR
2.2 Bioinformatic Tools for Metabolite Identification Via GC-MS
2.3 Bioinformatic Tools for Metabolite Identification Via LC-MS
3 Bioinformatic Tools for Detecting Metabolite Differences
3.1 Bioinformatic Tools for Reference-Based Metabolite Differentiation
3.2 Bioinformatic Tools for Multivariate Metabolite/Peak Differentiation
3.3 Principal Component Analysis
3.4 Partial Least Squares Discriminant Analysis
4 Bioinformatic Tools for Biomarker Discovery
5 Bioinformatic Tools for Biomedical Interpretation and Data Integration
6 Summary
References
Untargeted Metabolomics in Newborn Screening
1 Population-Wide Untargeted Screening
2 Screening for IEM Using UM
References
Glossary
Untargeted Metabolomics, Targeted Care: The Clinical Utilities of Bedside Metabolomics
1 Introduction
2 Metabolomics Joins the Diagnostic Front Seat
2.1 Monoamine Synthesis
2.2 Ornithine Metabolism
2.3 NAD(P)HX Repair System
2.4 Riboflavin Metabolism
2.5 Histidine Metabolism
2.6 The Diagnostic Rate Among Inborn Error of Metabolism
2.7 Automation of Data Interpretation
3 Metabolomic Fingerprinting: Identifying Diseases’ Biometrics and Finding New Disease Biomarkers
3.1 Peroxisome Biogenesis
3.2 Urea Cycle
3.3 Pyruvate Kinase
3.4 Glucose Transporter 1
3.5 Serine Metabolism
3.6 Pentose Phosphate Pathway and Polyol Metabolism
3.7 Metabolomics of Muscular Diseases
4 Future Perspectives
References
Glossary
Metabolomics in the Study of Human Mitochondrial Diseases
1 Introduction
2 Mitochondrial Metabolic Pathways
3 Mitochondrial Diseases
4 Diagnostic Tools for MDs
5 Metabolomics of MDs
6 Conclusion
References
Metabolomics of Rare Endocrine, Genetic Disease: A Focus on the Pituitary Gland
1 Introduction
2 Endocrine Diseases and Genetics
3 Metabolomics of Endocrine Disease
3.1 Metabolomics of Hypothalamus and Pituitary Gland Dysfunction
3.2 Growth Hormone Secretion Defects
3.2.1 Growth Hormone Excess: Acromegaly
3.2.2 Growth Hormone Deficiency
3.3 Hypercortisolism (Cushing’s Syndrome and Cushing’s Disease)
4 Conclusion
References
Metabolomics and Genetics of Rare Endocrine Disease: Adrenal, Parathyroid Glands, and Cystic Fibrosis
1 Introduction
2 Metabolomics of Adrenal Dysfunction
2.1 Hyperaldosteronism (Conn’s Syndrome)
2.2 Primary Adrenal Insufficiency
2.3 Metabolomics of Pheochromocytoma
3 Metabolomics of Parathyroid Dysfunction
3.1 Hypoparathyroidism
4 Exocrine Pancreatic Dysfunction: Metabolomics of Cystic Fibrosis
5 Conclusion and Future Perspectives
References
Metabolomic Role in Personalized Medicine: An Update
1 Introduction
2 Disease Metabolic Profiling “Metabotyping”
3 Personalized Medicine and Biomarker Discovery
4 Pharmacometabolomics
4.1 Prediction of Treatment Outcomes
4.2 Integrating Drug Metabolism Pathway Alteration
5 Conclusion
References
Lipidomic Profiling in Clinical Practice Using LC-MS
1 Introduction
2 Lipids and Lipoproteins: A Biochemical Approach
2.1 General Concepts
2.2 Lipids Mirror Present and Future Metabolic Health: Two Sides of the Same Problem
3 Clinical Relevance of the Lipidome
3.1 Lipids and NAFLD: Introduction Through LC-MS
4 Applications of LC-MS-Based Lipidomics in Clinical Practice
4.1 The OWLiver® Test
4.2 Other Diseases
5 Summary and Future Outlook
References
Bringing Human Serum Lipidomics to the Forefront of Clinical Practice: Two Clinical Diagnosis Success Stories
1 Introduction
2 Lipids and Lipoproteins: A Biochemical Approach
2.1 General Concepts
2.2 Lipids Mirror Present and Future Metabolic Health: Two Sides of the Same Problem
3 Clinical Relevance of the Lipidome
3.1 Lipids and NAFLD: Introduction to LC-MS
3.2 Lipoproteins and CVD: Introduction to NMR
4 Measurement Techniques for Characterization of Lipid Species and Lipoproteins
4.1 Main Techniques Used to Measure Lipid Species for Cardiometabolic Health Assessment
4.2 The Complementarity of Serum/Plasma LC/MS and NMR for Lipoprotein Analysis
4.3 LC-MS Lipidomics and 1H NMR Lipoprotein Profiling Technical Aspects (Table 2)
5 LC-MS Lipidomics and 1H NMR Lipoprotein Analysis in Clinical Practice
5.1 Clinical Application of LC-MS: The OWLiver® Test
5.2 Clinical Application of 1H NMR: The Liposcale Test
5.2.1 Individuals with Discordant Levels of LDL-C and LDL-P
5.2.2 Lipoprotein Profiles Associated with the Future Development of Type 2 Diabetes and Insulin Resistance
5.2.3 Other Diseases and Applications
6 Concluding Remarks and Future Perspective
6.1 Envisaged Risks and Limitations of Clinical Lipidomics
References
LC-MS-Based Population Metabolomics: A Mini-Review of Recent Studies and Challenges from Sample Collection to Data Processing
1 Introduction
2 Pre-Analytical Factors
2.1 Blood Samples
2.2 Urine Samples
3 Quality Assurance and Quality Control
4 Identification of Metabolites
4.1 Confidence Levels
4.2 Databases for Metabolite Identification
4.3 Data Processing Tools
5 Analytical Challenges
5.1 Variation of Metabolites
5.2 Missing Values
6 Statistical Analysis
7 Selected Case Studies
7.1 Pre-Analytical Procedures
7.2 Data Acquisition
7.3 Post-Acquisition Data Processing
8 Conclusion
References
Metabolomics and Transcriptomic Approach to Understand the Pathophysiology of Interstitial Lung Disease
1 Introduction
2 Types of ILD
2.1 Idiopathic Interstitial Pneumonia (IIP)
2.2 Autoimmune ILD
2.3 Hypersensitivity Pneumonitis (HP)
2.4 Sarcoidosis
2.5 Occupational and Environmental Exposure-Related Other ILDs
3 Metabolomics: An Emerging Tool in Clinical Research
3.1 Metabolomics in ILD
4 Transcriptomics: A Promising Omic Approach
4.1 Transcriptomics in ILD
5 Integration of Metabolomic and Transcriptomic Fingerprints
6 Challenges and Future Scope
References
Transferring Metabolomics to Portable Diagnostic Devices: Trending in Biosensors
1 Introduction
2 Biorecognition Receptors Used in the Biosensors for Metabolic Biomarkers
2.1 Enzyme-Based Biosensors
2.2 Antibody-Based Biosensors
2.3 Aptamer-Based Biosensors
3 Transducers for Detection of Metabolic Biomarkers
3.1 Electrochemical Detection
3.1.1 Amperometry/Voltammetry
3.1.2 Electrochemical Impedance Spectroscopy
3.2 Optical Detection
4 Advances in the Development of Biosensors for Metabolic Biomarkers
5 Conclusions and Future Perspectives
References