An empirical process for the design of high-throughput screening deck filters
An empirical process for the design of high-throughput screening deck filters
复制标题
DOI：
10.1021/ci050504m
复制
发表时间：
2006-05-01
影响因子：
5.6
通讯作者：
Stock, David A.
中科院分区：
文献类型：
--
作者：
Pearce, Bradley C.;Sofia, Michael J.;Stock, David A.
描述了一种用于客观鉴定和过滤导致高通量筛选（HTS）卡片组混杂的不期望的化合物的方法。已经开发了两种映射命中混杂的方法，将基于SMARTS的结构查询与历史主要HTS数据相关联。第一个比较预期的测定命中率与实际命中率。第二个检查单个化合物命中多个测定的倾向。数据的统计评价表明所得官能团过滤器和化合物混杂之间的相关性。这些数据证实了一些常用的过滤器，以及产生一些意想不到的结果。这些模型的应用HTS收集分类减少了12%的内部化合物的筛选考虑。这些研究结果的影响进一步讨论的背景下，HTS筛选集和组合库设计以及化合物的收购。
A process for objective identification and filtering of undesirable compounds that contribute to high-throughput screening (HTS) deck promiscuity is described. Two methods of mapping hit promiscuity have been developed linking SMARTS-based structural queries with historical primary HTS data. The first compares an expected assay hit rate to actual hit rates. The second examines the propensity of an individual compound to hit multiple assays. Statistical evaluation of the data indicates a correlation between the resultant functional group filters and compound promiscuity. These data corroborate a number of commonly applied filters as well as producing some unexpected results. Application of these models to HTS collection triage reduced the number of in-house compounds considered for screening by 12%. The implications of these findings are further discussed in the context of the HTS screening set and combinatorial library design as well as compound acquisition.