Reproducibility metrics for CRISPR screens

Reproducibility metrics for CRISPR screens
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DOI:
10.1101/2022.02.19.480892
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发表时间:
2022-02
期刊:
bioRxiv
影响因子:
--
通讯作者:
Maximilian Billmann;Henry N. Ward;Michael Aregger;M. Costanzo;B. Andrews;Charles Boone;J. Moffat;C. Myers
Maximilian Billmann;Henry N. Ward;Michael Aregger;M. Costanzo;B. Andrews;Charles Boone;J. Moffat;C. Myers
中科院分区:
其他
文献类型:
--
作者:
Maximilian Billmann;Henry N. Ward;Michael Aregger;M. Costanzo;B. Andrews;Charles Boone;J. Moffat;C. Myers

文献摘要

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CRISPR 筛选广泛用于系统地探讨表型到基因型的问题。与定义核心细胞适应性基因的早期 CRISPR 筛选相比,目前大多数努力的目标是识别区分细胞系、遗传背景或感兴趣的条件(例如药物治疗)的特定表型。虽然CRISPR相关技术展现出巨大的前景和快速的创新步伐,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开发和应用至关重要。具体来说,许多常用的量化屏幕质量的指标并不能准确测量特定上下文点击的再现性。我们强调报告与屏幕目的直接相关的再现性统计数据的重要性,并建议使用对特定上下文信号敏感的指标。
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.