Abstract

Recent advances in automated high-resolution fluorescence microscopy and robotic handling have made the systematic and cost effective study of diverse morphological changes within a large population of cells possible under a variety of perturbations, e.g., drugs, compounds, metal catalysts, RNA interference (RNAi). Cell population-based studies deviate from conventional microscopy studies on a few cells, and could provide stronger statistical power for drawing experimental observations and conclusions. However, it is challenging to manually extract and quantify phenotypic changes from the large amounts of complex image data generated. Thus, bioimage informatics approaches are needed to rapidly and objectively quantify and analyze the image data. This paper provides an overview of the bioimage informatics challenges and approaches in image-based studies for drug and target discovery. The concepts and capabilities of image-based screening are first illustrated by a few practical examples investigating different kinds of phenotypic changes caEditorsused by drugs, compounds, or RNAi. The bioimage analysis approaches, including object detection, segmentation, and tracking, are then described. Subsequently, the quantitative features, phenotype identification, and multidimensional profile analysis for profiling the effects of drugs and targets are summarized. Moreover, a number of publicly available software packages for bioimage informatics are listed for further reference. It is expected that this review will help readers, including those without bioimage informatics expertise, understand the capabilities, approaches, and tools of bioimage informatics and apply them to advance their own studies.

Highlights

  • The old adage that a picture is worth a thousand words certainly applies to the identification of phenotypic variations in biomedical studies

  • With the advances of fluorescent microscopy and robotic handling, imagebased screening has been widely used for drug and target discovery by systematically investigating morphological changes within cell populations

  • The bioimage informatics approaches to automatically detect, quantify, and profile the phenotypic changes caused by various perturbations, e.g., drug compounds and RNA interference (RNAi), are essential to the success of these imagebased screening studies

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Summary

Introduction

The old adage that a picture is worth a thousand words certainly applies to the identification of phenotypic variations in biomedical studies. With advances to automated highresolution microscopy, fluorescent labeling, and robotic handling, image-based studies have become popular in drug and target discovery. These image-based studies are often referred to as the High Content Analysis (HCA) [3], which focuses on extracting and analyzing quantitative phenotypic data automatically from large amounts of cell images with approaches in image analysis, computation vision and machine learning [3,4]. Bioimage informatics approaches were needed to automatically and objectively analyze large scale image data, extract and quantify the phenotypic changes to profile the effects of drugs and targets.

Example Image-based Studies for Drug and Target Discovery
Multicolor Cell Imaging-based Studies for Drug and Target Discovery
Caenorhabditis elegans Imagingbased Studies for Drug and Target Discovery
Quantitative Bioimage Analysis
Object Segmentation
Multidimensional Profiling Analysis
SVM-based Multivariate Profiling Analysis
Factor-based Multidimensional Profiling Analysis
Subpopulation-based Heterogeneity Profiling Analysis
Publicly Available Bioimage Informatics Software Packages
Summary
Exercises
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