Read more
Informationen zum Autor Dimitri Semizarov, PhD , is a Senior Group Leader in the Cancer Research Department of Abbott Laboratories' Global Pharmaceutical R&D. Dr. Semizarov leads cancer genomics research at Abbott, applying genomics technologies to enable personalization of cancer therapy. He is author or coauthor of more than twenty scientific articles and eight patent applications, as well as three book chapters (including two chapters in Wiley's Preclinical Development Handbook). Eric Blomme, DVM, PhD , Diplomate, American College of Veterinary Pathologists, is a Senior Project Leader for Cellular, Molecular, and Exploratory Toxicology in Global Pharmaceutical R&D at Abbott Laboratories. He has extensive drug discovery, toxicology, and screening experience working for Abbott, Pharmacia, Monsanto, Searle, Ohio State University, and Cornell University. Dr. Blomme has written over fifty journal articles and eight book chapters, and is a reviewer for multiple scientific journals in the fields of toxicology and pathology. Klappentext Early characterization of toxicity and efficacy would significantly impact the overall productivity of pharmaceutical R&D and reduce drug candidate attrition and failure. By describing the available platforms and weighing their relative advantages and disadvantages, including microarray data analysis, Genomics in Drug Discovery and Development introduces readers to the biomarker, pharmacogenomic, and toxicogenomics toolbox. The authors provide a valuable resource for pharmaceutical discovery scientists, preclinical drug safety department personnel, regulatory personnel, discovery toxicologists, and safety scientists, drug development professionals, and pharmaceutical scientists. Zusammenfassung Early characterization of toxicity and efficacy would significantly impact the overall productivity of pharmaceutical R&D and reduce drug candidate attrition and failure. Inhaltsverzeichnis Preface xiii 1. Introduction: Genomics and Personalized Medicine 1 Dimitri Semizarov 1.1. Fundamentals of Genomics 1 1.2. The Concept of Personalized Medicine 5 1.3. Genomics Technologies in Drug Discovery 8 1.4. Scope of This Book 13 References 20 2. Genomics Technologies as Tools in Drug Discovery 25 Dimitri Semizarov 2.1. Introduction to Genomics Technologies 25 2.2. Gene Expression Microarrays: Technology 27 2.2.1. Standard Microarray Protocol 27 2.2.2. Monitoring the Quality of Input RNA for Microarray Experiments 29 2.2.3. Specialized Microarray Protocols for Archived and Small Samples 31 2.2.4. Quality of Microarray Data and Technical Parameters of Microarrays 33 2.2.5. Reproducibility of Expression Microarrays and Cross-Platform Comparisons 35 2.2.6. Microarray Databases and Annotation of Microarray Data 38 2.2.6.1. Target Identification 39 2.2.6.2. Disease Classification 39 2.2.6.3. Compound Assessment 40 2.3. Gene Expression Microarrays: Data Analysis 47 2.3.1. Identification of Significant Gene Expression Changes 47 2.3.2. Sample Classification and Class Prediction with Expression Microarrays 48 2.3.3. Pathway Analysis with Gene Expression Microarrays 49 2.3.4. Common Problems Affecting the Validity of Microarray Studies 56 2.4. Comparative Genomic Hybridization: Technology 57 2.5. Comparative Genomic Hybridization: Data Analysis 69 2.6. Microarray-Based DNA Methylation Profiling 76 2.7. Microarray-Based MicroRNA Profiling 80 2.8. Technical Issues in Genomics Experiments and Regulatory Submissions of Microarray Data 86 2.8.1. Study of a Drug's Mechanism of Action by Gene Expression Profiling 87 2.8.2. Early Assessment of Drug Toxicity in Model Systems 88 2.8.3. Biomarker Identification in Disco...
