Introduction

摘要

Dear Readers, On behalf of the Journal of Biomolecular Screening (JBS), we are proud to present this year’s special issue focused on high-content screening (HCS). HCS was originally introduced by Taylor, Giuliano, and colleagues in their landmark article in JBS in 1997. They described HCS as an automated microscopy platform that permitted the quantification of fluorescent microscopy images through computerized image analysis. The original applications of this technology were tightly focused on the late stages of preclinical drug discovery, where it proved to be an effective alternative to expensive and time-consuming work in compound development. HCS represents the convergence of several mature technologies, including light microscopy, digital detectors such as CCD cameras or photomultiper tubes (PMT), robotics, and computer hardware to capture, store, and retrieve digitized images for computer-assisted analysis. As with other technologies that expand from their original implementation, HCS has begun to differentiate into new disciplines, such as high-content analysis (HCA), high-content informatics (HCI), and imaging cytometry. One of the defining features of this technology is its capacity to generate tens to hundreds of measurements per cell that describe the morphology, intensity, distribution, and location of fluorescent markers and probes at the cellular and subcellular levels. The information is then summarized at the whole-population or subpopulation levels. Although the potential for analyzing the information captured in such systems was appreciated at the time, it has taken years of incremental improvements to realize this potential. In this issue, we have included several contributions that highlight these advancements. In addition to advances in HCI, improvements in the hardware have also led to material benefits in the areas of primary drug discovery, target identification (such as RNAi screening), and developmental and basic biology. The throughput capacity of modern HCS platforms has enabled full-scale high-throughput screening (screens ranging from 100,000 compounds to more than 1 million compounds) using image-based endpoints. Some problems have proven to be highly intractable using standard microscopy platforms or even first-generation imaging platforms but have benefited from improvements to both informatics and instrumentation. Examples include the identification and study of rare cells within heterogeneous populations, live-cell kinetic responses, and 3D in vitro models. To give a real flavor of the breadth and depth of the scientific research themes that users of this technology now traverse, we offer for your perusal a range of cutting-edge reviews, basic research communications, and application notes. Collectively, these peer-reviewed articles represent the state of the art in this rapidly growing field of research. In this issue, we have sought to cover both the common problems and how, in many cases, solutions have led to significant advances in our understanding of the cellular processes that underlie diseases such as cancer, metabolic diseases, and neurodegeneration. The value of this technology in drug discovery and basic biomedical research cannot be overemphasized; indeed, the impact that HCS represents in these areas continues to be increasingly recognized by the scientific community at large. The future impact from discoveries using high-content imaging in life sciences will help us to better understand human diseases and improve health through basic science and drug discovery in ways that were not possible a few years ago. The articles presented here exemplify many of the advancements in this field. O. Joseph Trask, Jr. Head, Cellular Imaging Core The Hamner Institutes for Health Sciences 6 Davis Drive Research Triangle Park, NC 27709 E-mail: [email protected] Anthony Davies Director, High Content Research Facility (Trinity HCA) Institute of Molecular Medicine Phase 3 Trinity Health Science