Biochips as Pathways to Drug Discovery: 1st Edition (Hardback) book cover

Biochips as Pathways to Drug Discovery

1st Edition

Edited by Gary Hardiman

CRC Press

386 pages | 14 Color Illus. | 93 B/W Illus.

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pub: 2006-10-19
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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.


“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

Table of Contents

DNA Biochips — Past, Present, and Future: An Overview, G. Hardiman and A.A. Carmen


Evolution and Development of Biochips

Biochips Platforms: Comparisons and Contrasts


Three-Dimensional HydroArrays: Novel Microarrays for Genomic and Proteomic Studies, R. Fagnani, P. Tsinberg, and T.J. Pircher


Three-Dimensional HydroArrays

HydroArray Chemistry

Example of Focus Three-Dimensional HydroArrays

In-Vitro Diagnostic Applications

Protein Three-Dimensional HydroArrays



Biochip in Malaria for Antiparasitic Discovery, K. Le Roch and E. Winzeler



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



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


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



Toxicogenomics in Drug Safety Evaluation: Bridging Drug Discovery and Development, A.Y. Nie, M.K. McMillian, and P.G. Lord


Toxicogenomics Experimental Design

Case Study: PPAR Agonist Example

Summary and Conclusions


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


The INFINITI™ Platform

CYP2D6 Genotyping

Results and Discussion




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


Subjects and Methods

Blood Sampling and Leukocyte Isolation

RNA Extraction

Microarray Data Analysis


Evaluation of Gene Expression Profiles in Biopsy Tissues and White Blood Cells



ChIP-on-Chip: Analysis of Genomewide Protein Binding and Posttranslational Modifications, D. Robyr



ChIP-on-Chip: Brief History and Overview of the Method

Yeast ChIP-on-Chip and Beyond

ChIP-on-Chip and Biomedical Applications

Concluding Remarks



DNA Microarrays as Functional Genomics Tools for Cancer Drug Discovery, A. Bhattacharjee


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



Additional Notes


High-Throughput Microarray Analysis, S. Sheth

Developing the HT Array

Applications to Drug Discovery and Development

More Successful Clinical Trials

The Way Ahead


Laboratory Automation: Strategies for High-Volume Industrial Microarray Programs, A. Bittner and A.A. Carmen



Benefit of Automation to Microarray Experiments

Automation for Array Processing

Data Collection, Analysis, and Sample Tracking

Pitfalls of Automation



Association Studies: Practical and Theoretical Considerations for Drug Discovery, Evaluation, and Beyond, R.M. Kliman, F. Barany, N. Cohen, and R. Favis


Technical Considerations

Biological Considerations

Concluding Remarks


Approaches for Microarray Data Validation, S.E. Ilyin



Microarray Enterprise Information Management: What Is It and Why Is It Important? P. Morrison, P. Prakash, and S. Shams



Importance of Systematic Data Management for Quality Assurance

Data Management Needs at Each Step of Array Experiment



Quality Control of Microarray Data, H. Xiao, A. Leung, and L. Yieh


Algorithms Developed for Microarray Quality Control

Automation of Quality Control

Automatic Monitoring of Expression Data Improves Throughput of Data Processing and Data Quality



Microarray Data Normalization and Transformation, H. Xiao, L. Yieh, and H. Dai


Linear Normalization

Intensity-Dependent Normalization

Choosing a Normalization Method

Normalization for Oligonucleotide-Based Arrays

Performance of Normalization

Data Transformation



Amplification Strategies and DNA Biochips, B. Ruggeri, L. Soverchia, M. Ubaldi, R. Ciccocioppo, and G. Hardiman


Laser Capture Microdissection (LCM)

Microarray Target Labeling



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


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


Materials and Methods



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



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


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


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


About the Series

Drug Discovery Series

Learn more…

Subject Categories

BISAC Subject Codes/Headings:
MEDICAL / Pharmacy
SCIENCE / Biotechnology
SCIENCE / Chemistry / General