Z' Does Not Need to Be > 0.5.

Z' Does Not Need to Be > 0.5.
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DOI:
10.1177/2472555220942764
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发表时间:
2020-10
期刊:
SLAS discovery : advancing life sciences R & D
影响因子:
--
通讯作者:
Zweifach A
Zweifach A
中科院分区:
其他
文献类型:
--
作者:
Bar H;Zweifach A

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检测指标Z‘在决定是否可以进行高通量检测方面起到了关键的把关作用。虽然Z‘通常要求为>0.5,但这一期望并没有得到很好的支持。要求Z‘>0.5可能会阻止进行许多可能有用的表型和基于细胞的筛查,并导致在可能阻止发现活性的极端条件下进行其他分析。我们使用功率分析和一种新的数值模拟方法来确定Z‘如何在各种条件下反映检测性能。我们的结果表明,使用Z‘>0.5的分析比使用较低Z’的分析效果更好,但当选择适当的阈值时,使用Z‘<0.5的分析几乎总是可以在不产生太多假阳性的情况下找到有用的化合物。我们提供了一种方法,使研究人员能够估计如何为他们的检测设置适当的阈值。我们建议,与其总是要求Z‘>0.5,不如在根据目标的重要性和替代分析格式的局限性而能证明其合理性的情况下,使用Z’<0.5进行分析。
The assay metric Z’ has come to play a critical gatekeeping role in determining whether high-throughput assays can be performed. While Z’ is commonly required to be > 0.5, this expectation is not well supported. Requiring Z’ > 0.5 likely prevents many potentially useful phenotypic and cell-based screens from being conducted, and causes other assays to be conducted under extreme conditions that may prevent activity from being found. We used power analysis and a novel numerical simulation approach to determine how Z’ reflects assay performance under a variety of conditions. Our results show that assays with Z’ > 0.5 perform better than assays with lower Z’, but when an appropriate threshold is selected, assays with Z’ < 0.5 can almost always find useful compounds without generating too many false positives. We provide a method that will allow researchers to estimate how to set an appropriate threshold for their assay. We suggest that instead of always requiring Z’ > 0.5, assays with Z’ < 0.5 should be performed when they can be justified in terms of the importance of the target and the limitations of alternate assay formats.
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