Department of Computer Science and Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn 53127, Germany.
Bioinformatics and Computational Biology Graduate Program, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
Cell Syst. 2023 May 17;14(5):418-422.e2. doi: 10.1016/j.cels.2023.04.003.
CRISPR screens are used extensively to systematically interrogate the phenotype-to-genotype problem. In contrast to early CRISPR screens, which defined core cell fitness genes, most current efforts now aim to identify context-specific phenotypes that differentiate a cell line, genetic background, or condition of interest, such as a drug treatment. While CRISPR-related technologies have shown great promise and a fast pace of innovation, a better understanding of standards and methods for quality assessment of CRISPR screen results is crucial to guide technology development and application. Specifically, many commonly used metrics for quantifying screen quality do not accurately measure the reproducibility of context-specific hits. We highlight the importance of reporting reproducibility statistics that directly relate to the purpose of the screen and suggest the use of metrics that are sensitive to context-specific signal. A record of this paper's transparent peer review process is included in the supplemental information.
CRISPR 筛选被广泛用于系统地探究表型与基因型问题。与早期的 CRISPR 筛选定义核心细胞适应度基因不同,目前大多数的研究旨在鉴定区分细胞系、遗传背景或感兴趣的条件(如药物处理)的特定于上下文的表型。虽然 CRISPR 相关技术显示出巨大的潜力和快速的创新步伐,但更好地了解 CRISPR 筛选结果质量评估的标准和方法对于指导技术的发展和应用至关重要。具体而言,许多常用的用于量化筛选质量的指标并不能准确地衡量特定于上下文的命中的可重复性。我们强调报告与筛选目的直接相关的重现性统计数据的重要性,并建议使用对特定于上下文的信号敏感的指标。本文的透明同行评审过程记录包含在补充信息中。