Mass Spectrometry for Lipidomics: Methods and Applications. 2-Volume Set

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Volume 1
Half Title
Mass Spectrometry for Lipidomic: Methods and Applications. Volume 1
Copyright
Contents
Preface
1. Introduction to Lipidomics
1.1 Preface
1.2 Historical Perspective
1.3 Sampling and Preanalytics
1.4 Reference Materials and Biological Reference Ranges
1.5 Clinical Lipidomics
1.6 Identification and Annotation
1.7 Quantitation
1.8 Lipid Ontology
References
Part I: Analytical Methodologies in Lipidomics
2. Preanalytics for Lipidomics Analysis
2.1 Safety
2.2 Introduction
2.3 Sample Origin
2.4 Sample Collection
2.5 Tissue Homogenization
2.5.1 Mortar and Pestle
2.5.2 Rotor–Stator
2.5.3 Blender
2.5.4 Potter-Elvehjem
2.5.5 Bead Mill
2.6 Liquid–Liquid Extraction (LLE)
2.6.1 Folch Method
2.6.2 Bligh and Dyer (BD) Method
2.6.3 Modified Folch and Bligh/Dyer (BD) Methods
2.6.4 Rose and Oaklander (RO) Method
2.6.5 Matyash or Methyl-tert-Butyl Ether (MTBE) Method
2.6.6 BUME Method
2.6.7 Alshehry Method
2.6.8 Three-Phase Lipid Extraction (3PLE)
2.7 Resuspension and Solubilization
2.8 Automation
2.9 Tips and Tricks
Acknowledgments
References
3. Direct Infusion (Shotgun) Electrospray Mass Spectrometry
3.1 Introduction
3.2 Complexity of Crude Lipid Extracts
3.2.1 Main Lipid Classes in Mammalian Samples
3.2.2 Bond Types as Structural Features
3.2.3 Fatty Acids as the Major Building Blocks
3.2.4 Lipid Species and Double-Bond Series
3.3 Introduction to Mass Spectrometry of Lipids
3.3.1 Annotation of Lipid Structures Analyzed by MS
3.3.2 Isomers
3.3.3 Isobars and the Type-II Isotopic Overlap
3.4 Overview of Direct Infusion MS Workflows
3.5 Sample Preparation
3.5.1 Preanalytics – Sample Stability
3.5.2 Lipid Extraction
3.5.3 Solvents, Additives, and Lipid Concentration
3.5.4 Sample Derivatization
3.6 Direct Infusion
3.7 Mass Spectrometry Analysis
3.7.1 Electrospray Ionization of Lipids
3.7.2 Tandem Mass Spectrometry
3.7.3 Multidimensional MS Shotgun Lipidomics
3.7.4 High-Resolution Mass Spectrometry
3.8 Lipid Identification
3.8.1 Identification by MS/MS
3.8.2 Identification by HRMS
3.8.3 Consideration of Type-II Overlap
3.8.4 Identification Hierarchy
3.8.5 Caveats/Pitfalls
3.9 Lipid Quantification
3.9.1 Internal Standards
3.9.2 Type-I Isotopic Effect
3.9.3 Evaluation and Correction of Isotopic Overlap
3.9.4 Species Response
3.9.5 Calculation of Concentration
3.10 Data Analysis/Software
3.11 Limitations
3.12 Selected Applications
3.12.1 Analysis of Plasma
3.12.2 Analysis of Tissues and Cells
3.12.3 Analysis of Lipid Metabolism
3.13 Outlook
References
4. Liquid Chromatography – and Supercritical Fluid Chromatography – Mass Spectrometry
4.1 Introduction
4.2 Lipid Class Separation
4.2.1 Normal-Phase Liquid Chromatography
4.2.2 Hydrophilic Interaction Liquid Chromatography
4.2.3 Supercritical Fluid Chromatography
4.3 Lipid Species Separation
4.3.1 Reversed-Phase Liquid Chromatography
4.3.2 Nonaqueous Reversed-Phase Liquid Chromatography
4.4 Other Separation Approaches
4.4.1 Silver Ion Chromatography
4.4.2 Chiral Chromatography
4.4.3 Multidimensional Approaches
References
5. Mass Spectrometry Imaging of Lipids
5.1 Introduction
5.2 SamplePreparation for Mass Spectrometry Imaging of Lipids
5.2.1 Tissue Samples
5.2.2 Sectioning and Mounting
5.2.3 Cell Culture
5.2.4 Pre-processing
5.2.5 Handling and Storage
5.2.6 Formalin-Fixed Paraffin-Embedded Tissue
5.3 Desorption/Ionization Techniques used for MSI of Lipids
5.3.1 Matrix-Assisted Laser Desorption/Ionization (MALDI)
5.3.2 Secondary Ion Mass Spectrometry SIMS
5.3.3 MSI Methods Using Electrospray Ionization
5.3.3.1 Desorption Electrospray Ionization
5.3.3.2 Laser Ablation Electrospray Ionization and IR-Matrix-Assisted Laser Desorption-Electrospray Ionization
5.3.3.3 Nanospray Desorption Electrospray Ionization
5.4 CombiningIon Mobility of Lipids with MSI
5.5 OnTissue Chemical Derivatization for MSI
5.6 Quantificationin MSI
5.7 LipidIdentification for MSI
5.7.1 Types of Ions Generated by MSI
5.7.2 In-source Fragmentation Considerations
5.7.3 MSI Lipid Identification Using Accurate Mass
5.7.4 Deploying MS/MS for Lipid Identification in MSI
5.7.5 Isomer-Resolved MSI
5.8 Conclusions
References
6. Ion Mobility Spectrometry
6.1 Ion Mobility Spectrometry
6.1.1 Introduction
6.1.2 Ion Mobility Spectrometry Techniques and Platforms
6.1.2.1 Drift Tube Ion Mobility Spectrometry (DTIMS)
6.1.2.2 Traveling-WaveIon Mobility Spectrometry (TWIMS)
6.1.2.3 Trapped Ion Mobility Spectrometry (TIMS)
6.1.2.4 Field Asymmetric Ion Mobility Spectrometry (FAIMS)
6.1.3 Ion Mobility Resolving Power (Rp) Advancements
6.1.3.1 Cyclic IMS (cIM)
6.1.3.2 Standard Lossless Ion Manipulation (SLIM)
6.1.3.3 Tandem IMS
6.1.3.4 IMS Data Deconvolution Software Strategies
6.1.3.5 Drift Gas Dopants and Modifiers
6.1.4 Benefits of IMS for Lipidomics
6.1.4.1 Chemical Space Separation with IMS
6.1.4.2 Lipid Identification and Characterization with CCS
6.1.4.3 CCS for Lipid Structural Analysis
6.1.5 Lipidomic Applications with IMS
6.1.5.1 IMS in Imaging and Shotgun Lipidomics
6.1.5.2 IMS-MS/MS and Novel Speciation Approaches
6.1.6 Conclusions and Outlook of IMS for Lipidomics
References
7. Structural Characterization of Lipids Using Advanced Mass Spectrometry Approaches
7.1 Introduction
7.2 Structure and Position of Aliphatic Chains in Lipids
7.2.1 Double and Triple Bonds
7.2.1.1 Charge-Switch Derivatization of Fatty Acids
7.2.1.2 Ozone-Induced Dissociation
7.2.1.3 Paternò–Büchi Reaction
7.2.1.4 Epoxidation of Double Bonds
7.2.1.5 Acetonitrile-Related Adducts in APCI
7.2.1.6 Photodissociation of Unsaturated Lipids
7.2.1.7 Electron-Induced Dissociation of Unsaturated Lipids
7.2.2 Methyl Branching of Aliphatic Chains
7.2.3 Oxygen-Containing Functional Groups and Carbocyclic Structures
7.2.4 Stereospecific Position of Acyl Chain on Glycerol
7.3 Conclusions and Outlook
References
8. Lipidomic Identification
8.1 Overview
8.2 Chromatography
8.3 Mass Spectrometry
8.3.1 Exact Mass
8.3.2 Fragment Spectra
8.3.2.1 General Considerations
8.3.2.2 Fatty Acids
8.3.2.3 Oxylipins
8.3.2.4 Phospholipids
8.3.2.5 Sphingolipids
8.3.2.6 Glycerolipids
8.3.2.7 Sterols
8.3.3 Deep Structure Determination
8.4 Ion Mobility Spectrometry
8.5 Identification Workflows
References
9. Lipidomics Quantitation
9.1 Introduction to Lipidomics Quantitation
9.2 Principle of Quantitation
9.3 Internal Standards
9.4 Isotopic Correction
9.4.1 Isotopic Correction Type I
9.4.2 Isotopic Correction Type II
9.5 Common Approaches for Lipidomics Quantitation
9.5.1 Shotgun MS
9.5.2 Chromatography – MS
9.6 Validation
9.7 Quality Control (QC)
References
10. The Past and Future of Lipidomics Bioinformatics
10.1 Introduction
10.2 A Modular Lipidomics Workflow
10.2.1 Data Formats
10.3 Targeted Lipidomics: Assay Design and Raw Data Analysis with LipidCreator and Skyline
10.4 Untargeted Lipidomics: Assay Design and Raw Data Analysis with LipidXplorer
10.5 Standardization of Lipidomics Data with Goslin and lxPostman
10.6 Visualization and Lipidome Comparison with LUX Score and Beyond
10.7 Storage in Lipid Databases: What Is Currently There and What Should Be There
10.8 Outlook
10.8.1 Compatible Interfaces Between Modules
10.8.2 Quality Control
10.8.3 Reusability
References
Index
Volume 2
Half Title
Mass Spectrometry for Lipidomic: Methods and Applications. Volume 2
Copyright
Copyright Page
Contents
Preface
Part II: Lipidomic Analysis According to Lipid Categories and Classes
11. Fatty Acids: Structural and Quantitative Analysis
11.1 Fatty Acids/Acyl Groups as Analytical Targets
11.1.1 Fatty Acid Classification
11.1.2 Conventional Gas Chromatography (GC)–Mass Spectrometry (MS)
11.1.2.1 High-Resolution GC
11.1.2.2 DMOX (4,4-Dimethyloxazoline) Derivatization
11.1.2.3 Picolinyl Ester (3-Pyridylcarbinol)
11.1.3 GC-Solvent-Mediated (SM) Covalent Adduct Chemical Ionization (CACI)-MS/MS
11.1.3.1 Assignment of Double-Bond Position
11.1.3.2 Geometry of Double Bonds in Conjugated Linoleic Acids
11.1.3.3 Identification of Branched-Chain FA (BCFA)
11.1.3.4 Quantitative Analysis by SM Chemical Ionization and SM-CACI-MS/MS
11.1.4 Electrospray Ionization (ESI) Methods
11.1.4.1 Conventional ESI
11.1.4.2 Ozone-Induced Dissociation (OzID)
11.1.4.3 Paternò–Büchi (PB) Reaction
11.1.4.4 Ion–Ion Chemistry
11.1.4.5 Epoxidation
11.1.4.6 Silver Ion Liquid Chromatography-ESI
11.1.5 Characterization of Deuteration in Fatty Acids
11.1.6 Conclusion
References
12. Quantitation of Oxylipins in Biological Samples, Focusing on Plasma, and Urine
12.1 Introduction
12.2 Analysis of Oxylipins: Plasma, Tissues, and Cells
12.2.1 Planning of Sample Collection Preparation and Storage
12.2.2 Consideration of Experimental System, Focusing on Plasma and Serum
12.2.3 Obtaining and Handling Plasma for Oxylipin Analysis
12.2.4 Extraction of Oxylipins from Plasma
12.2.5 Setup of LC-MS/MS Analytical Method
12.2.6 Quality Assessment and Control
12.3 Challenges Presented by Oxylipin Isomers
12.3.1 Analytical Challenges of Isomers
12.3.2 Biological Considerations of Isomers
12.4 Analysis of Urine Oxylipin Metabolites
12.4.1 General Considerations
12.4.2 Prostaglandins (PGs)
12.5 Analysis of Oxylipins Attached to Phospholipids
12.6 Conclusions
Funding Acknowledgment
References
13. Mass Spectrometry for Analysis of Glycerolipids
13.1 Introduction
13.1.1 Gas Chromatography with Flame Ionization Detection for Fatty Acid Analysis
13.2 Monoacylglycerols (MAGs)
13.3 Diacylglycerols (DAGs)
13.3.1 Electrospray Ionization (ESI) for DGs
13.4 Triacylglycerols (TAGs)
13.4.1 Early Reports Described Structural Information that Comes from APCI-MS of TGs
13.4.2 Quantification of TGs by APCI-MS and APPI-MS
13.4.3 Covalent Adduct Chemical Ionization (CACI)
13.4.4 Quantification of TGs by ESI-MS Using Shotgun Lipidomics
13.4.5 Quantification of TGs by ESI-MS with HPLC/UHPLC Separation
13.4.6 Quantification of Regioisomers by ESI-MS
13.4.7 Ion Mobility MS for TGs
13.4.8 Oz-ID for TGs
13.4.9 Paternò–Büchi Reactions
13.4.10 Lipidomics
13.4.11 TG Quantification Using Lipidomics Software
13.4.12 Future Directions
Acknowledgments
References
14. Lipidomic Analysis of Glycerophospholipid Molecular Species in Biological Samples
14.1 Introduction
14.1.1 Diverse Functions and Structures of Glycerophospholipids
14.1.2 Pattern Recognition in Analysis of GPL
14.1.2.1 Recognition of a Building Block Pattern
14.1.2.2 Recognition of Fragmentation Patterns of GPL Classes
14.1.2.3 Molecular Mechanisms Underlying Fragmentation Patterns of GPL Classes
14.1.2.4 Practical Usage of Fragmentation Patterns of GPL Classes in Lipidomics
14.2 Fragmentation Patterns of GPL Classes
14.2.1 Choline Glycerophospholipid
14.2.1.1 Positive-Ion Mode
14.2.1.2 Negative-Ion Mode
14.2.1.3 Choline Lysoglycerophospholipids
14.2.2 Ethanolamine Glycerophospholipid
14.2.2.1 Positive-Ion Mode
14.2.2.2 Negative-Ion Mode
14.2.2.3 Phosphatidylinositol and Polyphosphoinositides
14.2.2.4 Phosphatidic Acid
14.2.2.5 Phosphatidylserine
14.2.2.6 Phosphatidylglycerol
14.2.2.7 Bis(Monoacylglycero)Phosphate
14.2.2.8 Cardiolipin
14.2.2.9 Anionic Lysoglycerophospholipids
14.2.2.10 Other Glycerophospholipids
Acknowledgments
References
15. Sphingolipids
15.1 Introduction
15.2 Sphingolipid Nomenclature
15.3 General Aspects of Sphingolipids in Mass Spectrometry
15.4 Sphingolipids in Vertebrates
15.4.1 Sphingoid Bases
15.4.2 Phosphorylated Sphingoid Bases
15.4.3 Ceramides Including Omega-Esterified Ceramides and 1-O-Acylceramides
15.4.3.1 Ceramides with Long and Very Long Acyl Chains
15.4.3.2 Skin Omega-Hydroxy Ceramides, Free, Esterified, and Protein-Bound
15.4.3.3 1-O-Acylceramides in Skin and Other Tissues
15.4.4 Ceramide 1-Phosphates
15.4.5 Sphingomyelins
15.4.6 Hexosylceramides
15.4.7 Neutral Complex Glycosphingolipids
15.4.8 Gangliosides
15.4.9 Sulfatides (Incl. Complex Sulfatides)
15.5 Stable Isotope Labeling
15.6 Imaging Mass Spectrometry (IMS) of Sphingolipids
15.7 Plants, Yeast, Fungi, Bacteria, Marine Organisms, and Sponges
References
16. Sterol Lipids
16.1 Introduction
16.1.1 Sterol in Cells
16.1.2 Oxysterols
16.1.3 Precursors of Cholesterol
16.1.4 Sterols and Oxysterol in Blood Plasma and Serum
16.1.5 Analytical Challenges
16.2 Analytical Methods
16.2.1 Classical GC-MS Methods for Sterol and Oxysterol Analysis
16.2.2 LC-MS/MS Analysis of Sterols and Oxysterols
16.2.3 LC-MS/MS Analysis of Sterols and Oxysterols Incorporating Derivatization
16.2.3.1 Derivatization to Picolinyl and Nicotinyl Esters
16.2.3.2 Derivatization to Dimethylglycyl Esters
16.2.3.3 Derivatization with Girard Hydrazine Reagents
16.2.3.4 Derivatization with 4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD)
16.2.4 Mass Spectrometry Imaging of Cholesterol and Oxysterols in Tissue
16.2.5 Analysis of Steryl Esters
16.3 Conclusions
Acknowledgments
Conflict of Interest Statement
References
17. Bile Acids
17.1 Introduction
17.2 Analytical Methods and Applications
17.2.1 Gas Chromatography–Mass Spectrometry (GC-MS)
17.2.2 Liquid Chromatography–Mass Spectrometry (LC-MS)
17.2.2.1 Early Technologies and ESI-Quadrupole MS
17.2.2.2 High-Resolution Mass Spectrometry (HR-MS)
17.2.3 Supercritical Fluid Chromatography (SFC)
17.3 Conclusions and Outlook
References
Part III: Lipidomic Applications
18. Lipidomic Profiling in a Large-Scale Cohort
18.1 Lipidomic Profiling in a Large-Scale Cohort Project
18.2 Sample Collection
18.3 Sample Preparation
18.3.1 Analytical Platform
18.3.2 Data Acquisition
18.3.3 Data Processing
18.3.4 Database Creation
18.3.5 Combination of Genome-Wide Association Studies
18.4 Conclusion
References
19. Cancer Lipidomics – From the Perspective of Analytical Chemists
19.1 Introduction
19.2 Investigating Dysregulated Lipids in Biological Samples
19.3 Samples
19.4 Preanalytical Considerations
19.5 Sample Preparation
19.6 Method Requirements
19.7 Validation and Quality Control
19.8 Data Processing, Statistical Analysis, and Data Reporting
19.9 Lipidomic Analysis in Cancer Research
References
20. Lipidomics in Clinical Diagnostics
20.1 What Do We Mean by “Clinical Diagnostics”?
20.2 Mass Spectrometry as an Enabler for Lipid-Based Clinical Tests
20.2.1 Vitamin D and Its Metabolites
20.2.2 The Trailblazing Ceramides
20.3 Bringing Lipidomics to the Clinic: Overcoming Current Challenges and Barriers
20.3.1 Raison D’être for Lipidomics in Patient Care: What Is the Clinical Utility?
20.3.2 The Reproducibility Issue: Is It Time to Harmonize?
20.3.3 From Consensus Values to Reference Intervals and True Values
20.4 Examples of Currently Existing Diagnostic Applications
20.4.1 Mitochondrial Fatty Acid -Oxidation and Organic Acid Metabolism
20.4.2 Fabry Disease
20.4.3 Gaucher Disease
20.4.4 Minimally Invasive Diagnostic Testing for NAFLD/NASH
20.4.5 Intrahepatic Cholestasis of Pregnancy
20.4.6 Steroid Hormone Measurements for CAH and Vitamin D Deficiency
20.4.6.1 Congenital Adrenal Hyperplasia
20.4.6.2 Vitamin D Deficiency
20.4.7 F2-Isoprostanes as Markers of Oxidative Stress
20.5 Final Comments
References
21. Lipidomics in Food Industry and Nutrition
21.1 Introduction
21.2 Lipids in Nutrition and Human Health
21.3 Fish, Shellfish, and Algae: Main Food Sources of Omega-3
21.4 Edible Plants and Vegetable Oils: Main Food Sources of Omega-6
21.5 Concluding Remarks
References
22. Lipidomics in Plant Science
22.1 Introduction
22.2 The Role of Phosphatidic Acid in Plant Response to Nutrients and Stress
22.3 The Roles of Phospholipids in Flowering and Diurnal Metabolism
22.4 Sphingolipid Analysis Has Facilitated the Discovery of Pathways Regulating Important Plant Cell Functions
22.5 Identification of a New Lipid Class in Plants Under Phosphate Stress
22.6 Oxidation and Head-Group Acylation of Membrane Lipids in Plant Stress
22.7 Triacylglycerols in Seeds and Leaves
22.8 Lipidomics to Monitor the Progress of Genetic Engineering to Alter Plant TG Level or Composition
22.9 The Future of Lipidomics in Plant Science
Acknowledgments
References
23. Lipidomics in Multi-Omics Studies
23.1 Introduction
23.2 Lipidomics in Multi-Omics Studies
23.3 Planning and Conducting Multi-Omics Studies
23.4 Analyzing Multi-Omics Data
23.5 Current Challenges
23.6 Conclusions and Outlook
References
24. Tracer Lipidomics
24.1 Flux Analysis and Stable Isotope Labeling Patterns
24.2 Experimental Conditions and Selecting the Right Tracer
24.3 Targeted Tracer Analysis
24.3.1 Fatty Acids
24.3.2 Phospholipids
24.4 Toward Untargeted Lipidome-Wide Tracer Analysis
24.4.1 Isotopic Effects and the Complexity of Tracer Analysis Mass Spectra
24.4.2 Technical Considerations
24.5 MS/MS Analysis as a Unique Approach to Study Fluxes at the Molecular Species Level
24.6 Concluding Remarks
References
25. Mass Spectrometry for Lipidomics: Methods and Applications – Aging and Alzheimer’s Disease
25.1 Introduction
25.2 Diversity in the Aging Process
25.3 Using Lipidomics as a Tool to Examine the Diversity in Aging
25.4 Age-Related Changes to the Plasma Lipidome
25.5 Age Is the Biggest Risk Factor for Alzheimer’s Disease
25.6 Interplay Between Lipids and Alzheimer’s Disease
25.7 Concept of Chronological and Metabolic Age
25.8 Development and Application of a Lipidomic Metabolic Age Score: The Next Steps
25.9 Conclusion
References
26. Lipidomics in Cell Biology
26.1 Lipid Composition of Organelles
26.1.1 Metabolic Bias Depending Upon Subcellular Location
26.1.2 Correlation Between Lipid Composition and Membrane Biophysical Properties
26.2 Lipid Composition Dictates Mechanisms of Intracellular Trafficking
26.2.1 The Endocytic Pathway
26.2.2 The Early Secretory Pathway
26.3 Multiomic Approaches to Investigate Cell Biology
26.4 Perspectives
References
27. Microbial Lipidomics
27.1 Introduction
27.2 Diversity of Lipid Structures in Intestinal Bacteria and Analytical Methods Using Mass Spectrometry
27.2.1 Fatty Acids
27.2.2 Glycerophospholipids
27.2.3 Sphingolipids
27.2.4 Bile Acids
27.2.5 Saccharolipids
27.3 New MS Technology
27.3.1 Chromatography Technology
27.3.2 Fragmentation
27.3.3 Identification Method for Unknown Structural Molecules
27.4 Conclusion and Future Perspective
References
Index