High-throughput imaging (HTI) is a powerful tool in the discovery of cellular disease mechanisms. While traditional approaches to identify disease pathways often rely on knowledge of the causative genetic defect, HTI-based screens offer an unbiased discovery approach based on any morphological or functional defects of disease cells or tissues. In this review, we provide an overview of the use of HTI for the study of human disease mechanisms. We discuss key technical aspects of HTI and highlight representative examples of its practical applications for the discovery of molecular mechanisms of disease, focusing on infectious diseases and host–pathogen interactions, cancer, and rare genetic diseases. We also present some of the current challenges and possible solutions offered by novel cell culture systems and genome engineering approaches.

高通量成像（HTI）是发现细胞疾病机制的有力工具。传统的识别疾病途径的方法通常依赖于致病性遗传缺陷的知识，而基于HTI的筛查则提供了基于疾病细胞或组织的任何形态或功能缺陷的无偏见的发现方法。在这篇综述中，我们提供了有关人类疾病机制研究中使用HTI的概述。我们讨论了HTI的关键技术方面，并重点介绍了其在疾病分子机制发现中的实际应用的代表性示例，重点关注传染病和宿主-病原体相互作用，癌症和罕见遗传病。我们还将介绍一些新颖的细胞培养系统和基因组工程方法所面临的当前挑战和可能的解决方案。