Proteomic and Metabolomic Approaches to Biomarker Discovery

Proteomic and Metabolomic Approaches to Biomarker Discovery

1st Edition - May 20, 2013

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  • Editor: Haleem Issaq
  • eBook ISBN: 9780123947956

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Description

Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis and modeling. This new standard effectively eliminates the differing methodologies used in studies and creates a unified approach. Readers will learn the advantages and disadvantages of the various techniques discussed, as well as potential difficulties inherent to all steps in the biomarker discovery process. A vital resource for biochemists, biologists, analytical chemists, bioanalytical chemists, clinical and medical technicians, researchers in pharmaceuticals, and graduate students, Proteomic and Metabolomic Approaches to Biomarker Discovery provides the information needed to reduce clinical error in the execution of research.

Key Features

  • Describes the use of biomarkers to reduce clinical errors in research
  • Includes techniques from a range of biomarker discoveries
  • Covers all steps involved in biomarker discovery, from study design to study execution

Readership

Biochemists, analytical chemists, bioanalytical chemists, biologists, medical technicians, clinical technicians, researchers in pharmaceuticals, graduate students and all interested in the field of biomarkers research.

Table of Contents

  • Preface

    List of Contributors

    Chapter 1. Biomarker Discovery: Study Design and Execution

    Abbreviations

    Introduction

    Definitions

    The Current State of Biomarker Discovery

    Study Design and Execution

    Errors in Study Design

    Errors in Study Execution

    Specificity of Proteins as Biomarkers

    Statistical Data Analysis

    Recommendations

    Concluding Remarks and Recommendations

    References

    Chapter 2. Proteomic and Mass Spectrometry Technologies for Biomarker Discovery

    Nonstandard Abbreviations

    Introduction

    Protein Biomarker Discovery and Development Pipeline

    Proteomic Samples

    Protein Identification by Mass Spectrometry

    Post-Translational Modifications as Disease Biomarkers

    Protein Quantification by Mass Spectrometry

    Biomarker Verification

    Biomarker Validation

    Limitations of Mass Spectrometry for Protein Biomarker Discovery

    Conclusions and Future Outlook: Integrated Biomarker Discovery Platform

    References

    Chapter 3. Tissue Sample Preparation for Proteomic Analysis

    Introduction

    Types of Tissues Available for MS-Based Proteomics

    Tissue Disruption/Homogenization

    Extraction/Solubilization Buffers

    Concluding Remarks

    References

    Chapter 4. Sample Preparation in Global Metabolomics of Biological Fluids and Tissues

    Abbreviations

    Introduction

    An Ideal Sample Preparation Method for Global Metabolomics?

    Sample Preparation Methods for Biofluids

    Tissue Metabolomics

    New Trends in Sample Preparation for Global Metabolomics

    Conclusions and Future Perspective

    References

    Chapter 5. Serum and Plasma Collection: Preanalytical Variables and Standard Operating Procedures in Biomarker Research

    Introduction

    Importance of Preanalytical Variables

    Standard Operating Procedures (SOPS)

    Sample Selection Considerations

    Human Blood and Its Components

    Other Biosamples

    Blood-Borne Pathogens, Universal Precautions, and Safety

    Human Subject Research Protections

    Conclusions

    References

    Chapter 6. Current NMR Strategies for Biomarker Discovery

    Introduction: Why NMR?

    NMR Hardware Advancement

    Sample Preparation for NMR Analysis

    One-Dimensional NMR Methods: 1H, 13C, 31P

    2D Methods

    Targeted Metabolic Profiling

    High-Resolution Magic Angle Spinning (HR-MAS) NMR Spectroscopy

    Magnetic Resonance Spectroscopy (MRS)

    NMR Data Processing and Preparation for Statistical Analysis

    NMR Metabolite Identification

    Future Directions and Conclusion

    References

    Chapter 7. Using Data-Independent Mass Spectrometry to Extend Detectable Dynamic Range without Prior Fractionation

    Introduction

    PAcIFIC and Quantification

    Proteome Profiling with PAcIFIC

    Perspectives

    References

    Chapter 8. Gas Chromatography/Mass Spectrometry-Based Metabonomics

    Introduction

    GC/MS in Metabonomics

    Strategies to Address Large-Scale Metabonomic Investigations

    Conclusion and Future Outlook

    References

    Chapter 9. Liquid Chromatographic Methods Combined with Mass Spectrometry in Metabolomics

    Introduction

    Chromatographic Methods for Metabolite Profiling

    Detection

    Quality Control, Data Analysis, and Biomarker Detection

    Metabolite Identification and Biomarker Validation

    Conclusions

    References

    Chapter 10. Capillary Electrophoresis–Mass Spectrometry for Proteomic and Metabolic Analysis

    Analysis of Metabolite Profiles Using Capillary Electrophoresis–Mass Spectrometry

    Analysis of Protein Expression Levels Using Capillary Electrophoresis–Mass Spectrometry

    Conclusion

    References

    Chapter 11. Current Gel Electrophoresis Approaches to Low-Abundance Protein Marker Discovery

    Introduction

    The Evolution of 2-DE Toward Proteomics Applications

    Low-Abundance Proteins Are Not Resolved by 2-DE Alone

    Enhancing Low-Abundance Proteins

    The Discovery of Protein Markers with 2-DE and Its Association with Low-Abundance Protein Enrichment

    Conclusions

    Dedication

    References

    Chapter 12. Two-Dimensional Difference in Gel Electrophoresis for Biomarker Discovery

    Introduction

    Gel Electrophoresis: Historical Perspective

    Two-Dimensional Differential In-Gel Electrophoresis

    Strengths and Weaknesses of 2D-PAGE and 2D-DIGE

    Application of 2D-DIGE to Biomarker Discovery

    Conclusions

    References

    Chapter 13. Affinity Targeting Schemes for Biomarker Research

    Introduction

    Affinity Targeting Methods

    Single Gene Expression Product Selection

    Post-Translational Modifications

    Abundant Protein Removal

    Conclusions

    References

    Chapter 14. Asp-Selective Microwave-Supported Acid Proteolysis

    Introduction

    Aspartate-Selective Acid Proteolysis

    Microwave-Supported Asp-Selective Acid Proteolysis

    Methods Development with Microwave-Supported Acid Hydrolysis

    Applications of Microwave-Supported Acid Hydrolysis

    Advantages and Disadvantages of Microwave-Supported Asp-Selective Acid Proteolysis

    References

    Chapter 15. Sample Depletion, Fractionation, and Enrichment for Biomarker Discovery

    Introduction

    Depletion

    Fractionation Procedures for Proteins and Metabolites

    Affinity Chromatography

    Isoelectric Focusing

    Size Exclusion Chromatography

    Conclusions

    References

    Chapter 16. Protein and Metabolite Identification

    Protein Identification

    Metabolite Identification in Global Metabolomics

    References

    Chapter 17. Quantitative Proteomics in Development of Disease Protein Biomarkers

    Introduction

    Quantitative Proteomic Profiling for Protein Biomarker Discovery

    Targeted Proteomic Validation of Biomarker Candidates

    Analyte Multiplexing and Sample Throughput

    Conclusion

    References

    Chapter 18. Mass Spectrometry and NMR Spectroscopy–Based Quantitative Metabolomics

    Metabolomics

    Comparative Chemometric Analysis versus Quantitative Metabolomics

    Mass Spectrometry

    NMR Spectroscopy

    Conclusions

    References

    Chapter 19. Multivariate Analysis for Metabolomics and Proteomics Data

    Study 1: Cancer Detection by Proteomics

    Study 2: Detection of Heart Disease by Metabolomics

    Conclusions

    References

    Chapter 20. Top-Down Mass Spectrometry for Protein Molecular Diagnostics and Biomarker Discovery

    Introduction

    Mass Spectrometry Hardware for Top-Down

    Sample Preparation and Separations

    Informatics

    Current Status

    Conclusion

    References

    Chapter 21. A Role for Protein–Protein Interaction Networks in the Identification and Characterization of Potential Biomarkers

    Introduction

    Network Analysis Using Protein–Protein Interaction

    Protein–Protein Interaction Databases

    Common Experimental Methodologies to Interrogate Protein–Protein Interactions

    Addressing the Background Problem

    Conclusion

    References

    Chapter 22. Reverse Phase Protein Microarray Technology: Advances into the Clinical Research Arena

    Introduction

    Origin of RPMA Technology

    RPMA in the Molecular Oncology Clinic

    Validation of Mass Spectrometry–Discovered Candidate Biomarkers by RPMA

    Conclusions and Vision for the Future

    References

    Chapter 23. Autoantibodies and Biomarker Discovery

    Introduction

    Proteomics Methods for the Detection of Autoantibodies

    Association of Autoantibodies with Disease States

    Challenges and Future Development

    References

    Chapter 24. MicroRNAs and Biomarker Discovery

    Abbreviations

    Introduction

    Basics of miRNA Biology, Function, and Detection

    Examples for MIRNA Biomarker Discovery Studies

    Conflict of Interest

    References

    Chapter 25. Imaging Mass Spectrometry of Intact Biomolecules in Tissue Sections

    Introduction

    Matrix Application

    Protein Analysis

    Peptides and Protein Digests

    Lipid Analysis

    Drug Analysis

    3D Imaging

    High-Speed Imaging

    Conclusions and Perspectives

    References

    Chapter 26. Mass Spectrometry–Based Approach for Protein Biomarker Verification

    Abbreviations

    Introduction

    MRM-MS Assay Generation for Protein Quantitation

    MRM-MS Assay Performance Characteristics for Biomarker Verification

    Sample Enrichment Strategies for Improving Biomarker Verification

    Mass Spectrometry–Based Strategies to Improve Biomarker Verification

    Stable Isotope-Labeled Internal Standards Used

    Bioinformatics Software for MRM-MS Assays and Biomarker Verification

    Selected Biomarker Verification Applications Based on MRM-MS

    Conclusions and Perspectives

    References

    Chapter 27. Mass Spectrometry Metabolomic Data Handling for Biomarker Discovery

    Metabolomics for Biomarker Discovery

    Mass Spectrometry-Based Metabolomics

    Targeted versus Untargeted Strategies

    Data Handling

    Variable Selection

    Data Modeling

    Model Validation

    Conclusions

    References

    Chapter 28. Analytical Methods and Biomarker Validation

    Introduction

    Discussion

    Experimental Design and Execution

    Biomarker Identification and Confirmation

    Biomarker Validation

    Conclusions

    References

    Index

Product details

  • No. of pages: 488
  • Language: English
  • Copyright: © Academic Press 2013
  • Published: May 20, 2013
  • Imprint: Academic Press
  • eBook ISBN: 9780123947956

About the Editor

Haleem Issaq

Haleem J. Issaq received his B.S. degree from the American College of Istanbul, Turkey, a M.S. degree from the Technion, Israel Institute of Technology, and a Ph.D. in analytical chemistry from Georgetown University in 1972. He was a Principal Scientist and Head of the Separation Technologies and Assay Development Group within the Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., located within the National Cancer Institute at Frederick, Maryland. His research interests include multidimensional separation of complex protein/peptide mixtures using liquid-phase-based separations (LC/LC, IEF/LC, and LC/CE), fast separation of estrogens, and use of HPLC/MS metabolomics for disease biomarker detection. He is the author or coauthor of over 350 scientific publications and the editor of A Century of Separation Science. He is the recipient of numerous awards, including Maryland Chemist of the Year.

Affiliations and Expertise

Emeritus Scientist, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, Maryland, USA

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