Design of signal windows in high throughput screening assays for drug discovery
Design of signal windows in high throughput screening assays for drug discovery
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DOI：
10.1177/108705719700200306
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发表时间：
1997-09-01
影响因子：
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通讯作者：
Lister, MD
中科院分区：
文献类型：
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作者：
Sittampalam, GS;Iversen, PW;Lister, MD
高通量筛选 (HTS) 测定用于从数十万种化合物中快速识别有前途的候选药物或先导化合物。因此，重要的是，测定应设计为区分活性和非活性化合物的反应以及背景噪音。我们引入了信号窗口的概念，它提供了信号之间一定程度的分离。这使得人们能够在存在变异性的情况下正确识别具有所需活性水平（称为“命中”）的新分子实体。设置和计算信号窗口的统计标准与说明性示例一起提供。结果表明，理想的信号窗口应该是筛选测定中最大信号的 2 个标准差 (SD)，尽管 1 SD 窗口大小是最小可接受的限度。当信号窗口设置为低于 2 SD 时，丢失“命中”的概率显着增加。
High Throughput Screening (HTS) assays are used to rapidly identify promising drug candidates or leads from hundreds of thousands of compounds. Hence, it is important that the assay should be designed to discriminate responses from the active and inactive compounds and the background noise. We introduce the idea of a signal window which provides a degree of separation between signals. This allows one to correctly identify new molecular entities with desired level of activity (called ''hits'') in the presence of variability, The statistical criteria for setting and calculating signal windows are presented along with illustrative examples, Results show that the ideal signal window should be 2 standard deviations (SD) of the largest signal in screening assays, although a 1 SD window size is the minimum acceptable limit, When signal windows are set below 2 SD, the probability of missing ''hits'' increases significantly.