Book contents
- Frontmatter
- Contents
- Contributors
- Preface
- Section one Overviews
- Section two Molecules for Chemical Genomics
- Section Three Basics of High-Throughput Screening
- Chapter 8 Essentials for High-Throughput Screening Operations
- Chapter 9 High-Content Analysis and Screening: Basics, Instrumentation, and Applications
- Chapter 10 Phenotypic Screens with Model Organisms
- Chapter 11 Screening Informatics and Cheminformatics
- Section Four Chemical Genomics Assays and Screens
- Section five Chemical Genomics and Medicine
- Index
- References
Chapter 9 - High-Content Analysis and Screening: Basics, Instrumentation, and Applications
from Section Three - Basics of High-Throughput Screening
Published online by Cambridge University Press: 05 June 2012
- Frontmatter
- Contents
- Contributors
- Preface
- Section one Overviews
- Section two Molecules for Chemical Genomics
- Section Three Basics of High-Throughput Screening
- Chapter 8 Essentials for High-Throughput Screening Operations
- Chapter 9 High-Content Analysis and Screening: Basics, Instrumentation, and Applications
- Chapter 10 Phenotypic Screens with Model Organisms
- Chapter 11 Screening Informatics and Cheminformatics
- Section Four Chemical Genomics Assays and Screens
- Section five Chemical Genomics and Medicine
- Index
- References
Summary
Basics of high-content analysis and screening
Drug discovery is now moving toward the implementation of cell- and whole organism–based assays in which the target is screened in a more physiologic context than in biochemical assays of isolated targets. Automated high-content analysis and screening (HCA/HCS) platforms are ideally suited to such chemical genomics approaches [1–4]. HCA/HCS encompasses an integrated process involving the use of fluorescent labeling techniques combined with automated multiwavelength fluorescent light microscopy and image analysis algorithms to extract multiparameter quantitative and qualitative data and information on cellular macromolecular structures and the localization of cellular components and to define the temporal dynamics of cellular functions [2, 5–17]. In automated imaging platforms, the acquisition of multiwavelength fluorescence images is integrated with image analysis algorithms and informatics tools to automate the unbiased capture and analysis of fluorescent images from millions of cells arrayed in the wells of microtiter plates [5–11]. What distinguishes HCA/HCS assays from the more typical single-parameter high-throughput screening (HTS) assay formats is their ability to acquire images in multiple fluorescent channels and by image analysis output multiparameter data from a variety of fluorescent measurements and features. These include fluorescence intensity and intensity ratios, texture within regions, cellular and subcellular morphometrics, and a total count of features [6, 9, 12–17]. HCA/HCS platforms have provided sufficient throughput and capacity to generate multiparametric cellular data at a scale that could be applied to drug discovery and high-throughput cell biology approaches, genome-wide RNA interference and overexpression strategies, phenotypic chemical biology screens, and cellular systems biology [2, 4–6, 11, 13–27]. Automated imaging platforms are being deployed in many phases of the drug discovery, basic research, and the chemical genomics process for target identification/validation, primary screening and lead generation, hit characterization, lead optimization, toxicology, biomarker development, diagnostic histopathology, and other clinical applications [2, 4–6, 11, 13–27].
- Type
- Chapter
- Information
- Chemical Genomics , pp. 108 - 120Publisher: Cambridge University PressPrint publication year: 2012