In the fiercely competitive pharmaceutical marketplace, your organization cannot afford to spend excess dollars developing drugs that will fail to get FDA approval or have profoundly poor characteristics. Biochips as Pathways to Drug Discovery takes a comprehensive look at how the industry faces these challenges, using new technologies such as biochips to reduce the cost of drug discovery and improve drug safety. The book explores the tools and skills required at each step of the discovery process when using biochips to determine biological outcomes.
The authors provide an in-depth review of the clinical and pharmacogenomic relevance of biochips, ChIP-chip assays, and high-throughput approaches. They discuss how biochips are used to develop biomarkers in the drug discovery process, primarily for gene expression profiling and Single Nucleotide Polymorphism (SNP) analysis. The book includes coverage of experimental theory, quality control, clinical laboratory sampling considerations, database concepts, industrial laboratory design, and the analysis of the resultant large data sets. It discusses the application of biochips to the study of malaria, toxicogenomics, and SNPs, as well as intellectual property and market overviews. The book concludes with a comprehensive overview of how these chips are employed from early target discovery through preclinical toxicology and on through to pharmacogenomic and proof of concept studies in humans.
Written in an easily accessible style, the breadth of coverage introduces the subject to those new to the field, while the depth of coverage forms a foundation for future work. The book gives you the knowledge required to leverage the technology into bona fide discoveries.
Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.
Introduction
Evolution and Development of Biochips
Biochips Platforms: Comparisons and Contrasts
References
Three-Dimensional HydroArrays: Novel Microarrays for Genomic and Proteomic Studies, R. Fagnani, P. Tsinberg, and T.J. Pircher
Introduction
Three-Dimensional HydroArrays
HydroArray Chemistry
Example of Focus Three-Dimensional HydroArrays
In-Vitro Diagnostic Applications
Protein Three-Dimensional HydroArrays
Conclusions
References
Biochip in Malaria for Antiparasitic Discovery, K. Le Roch and E. Winzeler
Introduction
Malaria
Life Cycle of the Malaria Parasite
Short Oligonucleotide vs. Long Oligonucleotide Microarray
Biological Relevance of Expression Profiling
The Use of Biochips for Elucidating the Mechanism of Drug Action
Vaccine Development
Conclusions.
References
Regional Variations in Intestinal ATP-Binding Cassette Transporter Expression Identified with a Global Error Assessment Model, D.M. Mutch, A. Petrov, J. B. German, G. Williamson, and M.-A. Roberts
Introduction
Global Error Assessment (GEA) Model
Regional Variations in ABC Transporter Expression in the Intestine
Validation 1: GEA Analysis of Microarray Data vs. Real-Time PCR
Validation 2: GEA Analysis of Microarray Data vs. an in Silico cDNA Data Set
Validation 3: GEA Analysis of Microarray Data vs. Protein Expression
Conclusion
References
Toxicogenomics in Drug Safety Evaluation: Bridging Drug Discovery and Development, A.Y. Nie, M.K. McMillian, and P.G. Lord
Introduction
Toxicogenomics Experimental Design
Case Study: PPAR Agonist Example
Summary and Conclusions
References
The Next Generation of Automated Microarray Platforms for a Multiplexed CYP2D6 Assay, P. Kim, Y.-K. Ken Fu, V. Mahant, F. Kureshy, G. Hardiman, and J. Corbeil
Introduction
The INFINITI™ Platform
CYP2D6 Genotyping
Results and Discussion
Conclusion
Acknowledgments
References
Biopsy and RNA Extraction Procedures of Muscle and Adipose Tissue for Microarray Gene-Expression Profiling, M.B.A. van Doorn, M.J.B. Kemme, M. Ouwens, E.J. van Hoogdalem, X. Liu, Q.S. Li , C.R. Jones, M.L. de Kam, J. Burggraaf, and A.F. Cohen
Introduction
Subjects and Methods
Blood Sampling and Leukocyte Isolation
RNA Extraction
Microarray Data Analysis
Results
Evaluation of Gene Expression Profiles in Biopsy Tissues and White Blood Cells
Discussion
References
ChIP-on-Chip: Analysis of Genomewide Protein Binding and Posttranslational Modifications, D. Robyr
Abstract
Introduction
ChIP-on-Chip: Brief History and Overview of the Method
Yeast ChIP-on-Chip and Beyond
ChIP-on-Chip and Biomedical Applications
Concluding Remarks
Acknowledgments
References
DNA Microarrays as Functional Genomics Tools for Cancer Drug Discovery, A. Bhattacharjee
Abstract
Introduction: DNA Microarrays in Drug Discovery
From Cancer Classification to Drug Discovery
Hunting and Screening Approaches in Drug Discovery
The Era of DNA Microarrays
Impact of Mechanism-Based Studies in Cancer Drug Discovery and Development
Future of Microarrays in System-Level Overview of Cancer and Therapeutic Intervention
Conclusions
Acknowledgments
Additional Notes
References
High-Throughput Microarray Analysis, S. Sheth
Developing the HT Array
Applications to Drug Discovery and Development
More Successful Clinical Trials
The Way Ahead
References
Laboratory Automation: Strategies for High-Volume Industrial Microarray Programs, A. Bittner and A.A. Carmen
Abstract
Introduction
Benefit of Automation to Microarray Experiments
Automation for Array Processing
Data Collection, Analysis, and Sample Tracking
Pitfalls of Automation
Summary
References
Association Studies: Practical and Theoretical Considerations for Drug Discovery, Evaluation, and Beyond, R.M. Kliman, F. Barany, N. Cohen, and R. Favis
Introduction
Technical Considerations
Biological Considerations
Concluding Remarks
References
Approaches for Microarray Data Validation, S.E. Ilyin
Acknowledgments
References
Microarray Enterprise Information Management: What Is It and Why Is It Important? P. Morrison, P. Prakash, and S. Shams
Abstract
Introduction
Importance of Systematic Data Management for Quality Assurance
Data Management Needs at Each Step of Array Experiment
Conclusions
References
Quality Control of Microarray Data, H. Xiao, A. Leung, and L. Yieh
Introduction
Algorithms Developed for Microarray Quality Control
Automation of Quality Control
Automatic Monitoring of Expression Data Improves Throughput of Data Processing and Data Quality
Conclusions
References
Microarray Data Normalization and Transformation, H. Xiao, L. Yieh, and H. Dai
Overview
Linear Normalization
Intensity-Dependent Normalization
Choosing a Normalization Method
Normalization for Oligonucleotide-Based Arrays
Performance of Normalization
Data Transformation
Conclusion
References
Amplification Strategies and DNA Biochips, B. Ruggeri, L. Soverchia, M. Ubaldi, R. Ciccocioppo, and G. Hardiman
Introduction
Laser Capture Microdissection (LCM)
Microarray Target Labeling
Conclusion
References
Ribo-SPIA™, a Rapid Isothermal RNA Amplification Method for Gene Expression Analysis, A. Dafforn, P. Chen, G.Y. Deng, M. Herrler, D.M. Iglehart, S. Koritala, S.M. Lato, S. Pillarisetty, R. Purohit, L. Turner, M. Wang, S. Wang, and N. Kurn
Introduction
Ribo-SPIA™: A Novel Method for Global Isothermal Linear Amplification of mRNA
Ribo-SPIA™ Protocol for Rapid Robust Amplification of Total mRNA in Small Total RNA Samples
Accuracy, Reproducibility, and Linearity of Ribo-SPIA™ Assessed by qPCR
Expression Analysis Using the Ribo-SPIA™ Amplification and GeneChip® Arrays
Performance of Ribo-SPIA™-Amplified Product on Two-Color Spotted Arrays
Conclusions
Materials and Methods
Acknowledgments
References
Genomics, Transcriptomics, and Proteomics: Novel Detection Technologies and Drug Discovery, P. Stafford
Background and Introduction
Fostering Biological Knowledge: Cross-Discipline Data
Unifying the Biological (Data) World
The Legacy of Expression Arrays
Systems Biology — Driving Drug Development through Data Integration
Controls and Standards
Biomarkers and the History of Genetics
SNP Detection
Some Detection Technologies of Interest
NonSNP Technology: The Protein Chip, Microfluidics, and Assorted Engineering Marvels
Microfluidics and Alternate Small-Scale Detection Devices
Other Biomolecule Detection Methods
SNP Detection: Major Commercial Technologies
SNP Detection Diversity
SNP Detection: Electronic Detection
SNP Detection: Bead-Based
The SNP Chip: Flow-Through Methods
SNP Detection: Sequence-Based
SNP Detection: Alternate Detection Methods
SNP Technology: Analysis Software
Discussion
References
Intellectual Property Issues for DNA Chips and Microarrays, V.G. Norton
Overview of Patent Law Statutes and Guidelines Applied to Genomic Inventions
IP Implications for DNA Chips and Microarrays
Other Solutions to Promote Innovation: Free Sharing of SNP Information
Conclusion
Biochips: Market Drivers and Commercial Prospect, J. Xu
DNA Microarrays: An Established and Expanding Business .
The Evolving Industry Landscape
Continued Market Drivers and Commercial Prospect
Protein Arrays: An Industry in Take-Off
Emerging Industry LandscapeMarket Drivers and Commercial Prospects
Biochip Industry: The Next 5 Years
References
A Pharmaceutical Perspective for Microarrays and Biochips: Current-Market Overview and Future Trends
L. Milne
Microarrays: Current-Market Overview
Microarrays: Company Profiles
Microarrays: Future Market Directions and Hurdles
References
“The authors of this volume provide an in-depth review of the clinical and pharmacogenomic relevance of biochips, ChIP-chip assays, and high-throughput approaches. … The book includes coverage of experimental theory, quality control, clinical laboratory sampling considerations, database concepts, industrial laboratory design, and the analysis of the resultant large data sets. … Written in an easily accessible style, the breadth of coverage introduces the subject to those new to the field, while the depth of coverage forms a foundation for future work.”
— In Anticancer Research, Vol. 27, No. 3B, May/June 2007"This book is a must have for students who use biochips in their graduate work or others initiating efforts in these areas . . . In summary, Biochips as Pathways to Drug Discovery provides a broad yet detailed look at the use of DNA microarrays in drug discovery."
– Matthew D. Disney, The University at Buffalo, The State University of New York, in ChemMedChem, 2008, No. 3